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Review

Antitumor Profile of Carbon-Bridged Steroids (CBS) and Triterpenoids

by
Valery M. Dembitsky
1,*,
Tatyana A. Gloriozova
2 and
Vladimir V. Poroikov
2
1
Centre for Applied Research, Innovation and Entrepreneurship, Lethbridge College, 3000 College Drive South, Lethbridge, AB T1K 1L6, Canada
2
Institute of Biomedical Chemistry, Bldg. 8, 10 Pogodinskaya Str., 119121 Moscow, Russia
*
Author to whom correspondence should be addressed.
Mar. Drugs 2021, 19(6), 324; https://doi.org/10.3390/md19060324
Submission received: 13 May 2021 / Revised: 1 June 2021 / Accepted: 1 June 2021 / Published: 3 June 2021
(This article belongs to the Special Issue Pharmacological Activity and Biomedical Potential of Marine Antitumor Agents)
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Abstract

:
This review focuses on the rare group of carbon-bridged steroids (CBS) and triterpenoids found in various natural sources such as green, yellow-green, and red algae, marine sponges, soft corals, ascidians, starfish, and other marine invertebrates. In addition, this group of rare lipids is found in amoebas, fungi, fungal endophytes, and plants. For convenience, the presented CBS and triterpenoids are divided into four groups, which include: (a) CBS and triterpenoids containing a cyclopropane group; (b) CBS and triterpenoids with cyclopropane ring in the side chain; (c) CBS and triterpenoids containing a cyclobutane group; (d) CBS and triterpenoids containing cyclopentane, cyclohexane or cycloheptane moieties. For the comparative characterization of the antitumor profile, we have added several semi- and synthetic CBS and triterpenoids, with various additional rings, to identify possible promising sources for pharmacologists and the pharmaceutical industry. About 300 CBS and triterpenoids are presented in this review, which demonstrate a wide range of biological activities, but the most pronounced antitumor profile. The review summarizes biological activities both determined experimentally and estimated using the well-known PASS software. According to the data obtained, two-thirds of CBS and triterpenoids show moderate activity levels with a confidence level of 70 to 90%; however, one third of these lipids demonstrate strong antitumor activity with a confidence level exceeding 90%. Several CBS and triterpenoids, from different lipid groups, demonstrate selective action on different types of tumor cells such as renal cancer, sarcoma, pancreatic cancer, prostate cancer, lymphocytic leukemia, myeloid leukemia, liver cancer, and genitourinary cancer with varying degrees of confidence. In addition, the review presents graphical images of the antitumor profile of both individual CBS and triterpenoids groups and individual compounds.

Graphical Abstract

1. Introduction

In both natural and synthetic steroids, when an additional ring is formed within the steroid skeleton, through a direct bond between any two carbon atoms (or more) of the steroid ring system or an attached side chain, such steroids (or triterpenoids) are called carbon-bridged steroids [1,2]. Analyzing the literature data from 1920, we concluded that the first mention of cyclopropane-containing hormones appeared in the mid-1930s of the twentieth century [2,3,4]. Steroids containing a cyclopropane ring in the side chain, such as gorgosterol, were first isolated from marine organisms in the early 1940s [4,5,6], and other 22,23-cyclopropyl sterols, such as dimethyl-gorgosterol, acanthasterol, demethylacanthasterol, acanthastanol, and 9,11-secogorgosterol, all of which have 22R, 23R and 24R configurations, have been isolated from marine sources [7,8,9,10,11,12]. Natural triterpenes containing a cyclopropane ring, and called cycloartanes, were first found in the early 1950s [13,14,15].
Natural carbon-bridged steroids predominantly contain an additional cyclopropane ring, and to a lesser extent cyclobutane, cyclopentane, cyclohexane or cycloheptane, although synthetic CBS can contain a wide variety of additional rings. It was found that all these groups of CBS exhibit a wide range of biological activities [16,17,18,19,20,21].
Over the past 30–40 years, scientists have made great efforts to search for antitumor agents, among both natural and synthetic compounds, for use in practical and experimental medicine [22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]. In our opinion, natural and synthetic carbon-bridged steroids or similar triterpenoids can be excellent anticancer agents, as they exhibit a wide range of biological activities and, predominantly, antitumor activity.
Our review focuses on this topic, and we consider about 300 natural, semi-, and synthetic carbon-bridged steroids and similar triterpenoids, many of which show pronounced antitumor activity.

2. Cyclopropane Containing Steroids and Triterpenoids

A unique steroid containing a 5,19-cycloergostane skeleton, (3β,5β,6β,7α,22E,24ξ)-5,19-cycloergost-22-ene-3,6,7-triol, named hatomasterol (1) was found in the extracts of the Okinawan sponge Stylissa sp., and an isolated compound demonstrated cytotoxicity against HeLa cells in vitro [47]. Chemical structures 1–18 are shown in Figure 1, and their biological activity is shown in Table 1.
Cycloartane derivatives are widely distributed in terrestrial plants, but only a few were obtained from the seaweeds and marine invertebrates. Thus, cycloartane triterpene 3-hydroxy-cycloarta-23,25-dien-28-oic acid (2) was found in the red alga Galaxaura sp. [48]. Cycloartenol (3), 24-methylene cycloartenol (4), and cycloartanol (5) have been detected in brown alga Fucus spiralis and F. krishnae (Phaeophyceae) [49,50], in the marine green algae Enteromorpha intestinalis and Ulva lactuca [51], in a freshwater species of single-celled alga Euglena gracilis [52], in a yellow-green unicellular freshwater alga Monodus subterraneus [53], and in the subarctic moss Dicranum elongatum [54]. Cycloartenol (3) was also found in a single-cell green alga Chlamydomonas reinhardtii [55], a single-celled green algae Chlorella ellipsoidea [56], and cycloartenol is found in a ubiquitous green alga Prototheca wickerhamiiin [57], in the marine alga Aurantiochytrium sp. [58], and in the red seaweed Laurencia dendroidea [59].
Interestingly, cycloartenol (3) is the sterol precursor in photosynthetic organisms such as amoebae Naegleria lovaniensis, N. gruberi and the soil amoeba Acanthamoeba polyphaga using [l-14C] acetate in the biosynthesis of all steroids in the genus Amoeba [60,61]. In addition to cycloartenol, 24-methylene cycloartenol (4), cycloartanol (5), and 31-norcycloartenol (34) were also identified using NMR spectra in Naegleria lovaniensis, N. gruberi (Milankovic 2017) [62], and Acanthamoeba polyphaga [63], and cycloartenol was found in the amoeba Dictyostelium discoideum [57].
The crude aqueous and EtOAc extracts of tropical Atlantic green alga Penicillus capitatus (Bryopsidales) showed potent inhibition of the ubiquitous marine fungal pathogen Lindra thallasiae. The authors studied the lipid composition and found two sulphate esters named capisterones A (6) and B (7) [64]. The MeOH extract of the green alga Tuemoya sp. showed inhibitory activity against Herpes Zoster protease, and the extract yielded two steroids, cycloartane-3,28-disulfate-23-ol (8) and cycloart-24-en-23-one-28-sulfate-3-ol (9). Both compounds demonstrated activity against both VZV and CMV protease in the 4–7 μM range [65]. Three cycloartenol sulfates (8, 10, and 11) that inhibit protein tyrosine kinase pp60v-src were isolated from a tropical deep-water siphonaceous green alga Tydemania expeditions [66].
Four steroids, 3β-methyl-25-dihydroxycycloart-23-en-29-oate 3-sulfate (12), 3β-methyl-hydroxy-25-methoxycycloart-23-en-29-oate 3-sulfate (13), 3β-hydroxy-25-methoxycycloart-23-ene 3-sulfate (14) and (3β-hydroxycycloart-24-en-23-one 3-sulfate (15) were isolated from Vietnamese red alga Tricleocarpa fragilis. All isolated steroids showed potent inhibitory activity against yeast α-glucosidase with IC50 values of 16.6, 36.3, 30.2 and 6.5 µM, respectively [67]. The Far Eastern sea cucumber Eupentacta fraudatrix (Class Holothuroidea) are sedentary and feed on plankton, algae, and organic debris extracted from bottom silt and sand that is passed through the alimentary canal. Sulfated cycloartane (16), which was found in sea cucumber extract, appears to be a metabolite of algae origin [68].
Two cycloartane-type triterpenoids, 3-epicyclomusalenol (17), and cyclosadol (18) were isolated from brown algae Kjellmaniella crassifolia. Both compounds have been reported to have moderate chemo preventive effects [69,70]. Six cycloartanes, 24-hydroperoxycycloart-25-en-3β-ol (19, chemical structures 19–36 are shown in Figure 2, and their biological activity is shown in Table 2), cycloart-25-en-3β24-diol (20), 25-hydroperoxycycloart-23-en-3β-ol (21), cycloart-23-en-3β,25-diol (22), cycloart-23,25-dien-3β-ol (23), and cycloart-24-en-3β-ol (24) were isolated from ethanol extract of marine green alga Cladophora fascicularis [71]. The small, floating plant Spirodela punctata (or Landoltia punctata, also known as dotted duckmeat) is widespread in the Hawaiian Islands, Southern and Eastern United States, and synthesized cycloartane glycoside (25). The biological activity of this glycoside has not been studied [72].
The uncommon 24-homo-30-nor-cycloartane (26), produced by the endophytic fungus Mycoleptodiscus indicus FT1137, which was isolated from the Hawaiian Stenocereus sp. (family Cactaceae). Obtained compound demonstrated cytotoxic activity against human ovarian cancer cell line A2780 [73]. An endophytic fungus Trichoderma harzianum which isolated from Kadsura angustifolia produce 3,4-secocycloarta-4(28),24-(Z)-diene-3,26-dioic acid named nigranoic acid (27) and its highly oxygenated derivatives [74], and another endophytic fungus Umbelopsis dimorpha transformed the triterpene nigranoic acid into its derivatives (28) and (29) [75]. A steroid called cycloeucalenone (30) was isolated from an unidentified fungus collected from New Jersey [76]. Akihisa and co-workers reported that the fungus Glomerella fusarioides transformed cycloartenol (4) to cycloartane-3,24-dione (31), rare 4α,4β,14α-trimethyl-9β,19-cyclopregnane-3,20-dione (32) and 24,25-dihydroxycycloartan-3-one (33) [77].
31-Norcycloartenol (34) and cycloartanol (5) are found in a fern oil from the family Polypodiaceae, Polypodium vulgare [78], and 29-nor-cycloartanol (35) and cycloartanol (5) was detected in a flowering plant in the spurge family Euphorbiaceae, Euphorbia balsamifera [79].
The Parthenium argentatum (commonly known as guayule) extract contained a cytotoxic steroid named argentatin A (36), which showed a cytotoxic effect against the human colon cancer cell lines (HCT15, HCT116, and SW620) and normal epidermal keratinocytes cell line [80].
The triterpenoids named xuetonglactones E (37, chemical structures 37–52 are shown in Figure 3, and their biological activity is shown in Table 3) and F (38) were isolated from the stems of an evergreen climbing shrub Kadsura heteroclita. Both compounds showed potent cytotoxic activities against human cervical cancer cell lines (HeLa) and human gastric cancer cells (BGC 823) [81]. The rare ring-A seco-cycloartane carbon skeleton, coronalolide methyl ester (39), and methyl coronalolate acetate (40) were isolated from the leaves and stems of Gardenia coronaria. Both compounds showed broad cytotoxic activity when evaluated against a panel of human cancer cell lines [82]. Cytotoxic cycloartane triterpenoid, 25-O-acetyl-7,8-didehydrocimigenol-3-O-β-d-(2-acetyl)-xylopyranoside (41) was found from Cimicifuga foetida [83]. This compound demonstrated antitumor activity against cancerous MCF-7, HepG2/ADM, HepG2 and HELA cell lines. A medicinal plant Schisandra chinensis contains two triterpenoids, kadsuphilactone B (42), and schinalactone D (43), which showed anti-HIV-1 activity and antitumor effects [84].
Cycloartane derivatives, cimyunnin A (44) with an unusual fused cyclopentenone ring G, together with cimyunnin D (45), possessing a highly rearranged c-lactone ring F, were found in the fruit of Cimicifuga yunnanensis and their structures were determined using physical-chemical methods [85]. 3,4-Seco-cycloartane triterpenoid which had rearranged 5/6 consecutive carbocycle rings C/D, named ananosins A (46), was isolated from the stems of Kadsura ananosma [86].
Cycloartenol triterpene saponin, 7,8-didehydro-24S-O-acetylhydroshengmanol-3-O-β-d-galactopyranoside named shengmaxinside C (47) has been isolated from the ethyl acetate soluble fraction of an ethanol extract of Cimicifuga simplex roots [87]. A 24-methylene-cycloartane-3β,16β,23β-triol, named longitriol (48) was isolated from ethanolic extract of the leaves of Polyalthia longifolia var. pendula, and shown cytotoxic effects against four human cancer cell lines and found to be most active against cervical carcinoma cell lines [88].
The aerial parts of Cimicifuga heracleifolia contained a 9,19-cycloartane-type triterpene, cimiheraclein A (49) and showed weak activity against human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480) [89]. The rhizomes of Beesia calthifolia resulted in the isolation of cycloartane derivative (50) [90], and Abies faxoniana is the source of cycloartane derivative (51) with spiro-side chain [91]. The 3,4-seco-cycloartane, macrocoussaric acid F (52) has been isolated from Coussarea macrophylla [92].
Unique steroids, 4,4,8β-Trimethyl-7α-hydroxy-13α, 14α-methano-18-nor-5α-androsta-1-ene-3,17-dione, named malabanone A (53) and 3,3,8β-trimethyl-7α-hydroxy-13α,14α-methano-A (4),18-dinor-5α-androstane-2,17-dione named malabanone B (54), which incorporate a unique tricyclo [4.3.1.01,6] decane unit in the structures, were isolated from the stem bark of Ailanthus malabarica. The authors suggest that both steroids are biosynthesized from ailanthol (55, (23R,24S)-4,4,8β-Trimethyl-13α,14α-methano-21,23:24,25-diepoxy-18-nor-5α-cholesta-20-ene-3α,7α-diol), which was also isolated from this plant [93]. Chemical structures 53–65 are shown in Figure 4, and their biological activity is shown in Table 4.
Several steroids with an incorporated cyclopropane unit at positions 14 and 18 named ailanthusins A (56), B (57) and D (58) have been found and isolated from the CH2Cl2 extracts of Thailand rainforest tree Ailanthus triphysa [94]. The dichloromethane extract of the air-dried leaves of Dysoxylum mollissimum afforded two glabretal-type triterpenoids (59 and 60) [95]. Cytotoxic glabretal triterpene, pancastatin B (61) was detected in the immature fruits of Poncirus trifoliata. This compound exhibited selective cytotoxicity against PANC-1 pancreatic cancer cells under low-glucose stress conditions [96]. Another glabretal-type triterpenoid named dictabretol D (62) was isolated by activity-guided fractionation from the root bark of Dictamnus dasycarpus (Rutaceae). This triterpenoid demonstrated inhibition of proliferation of activated T cells [97]. A CHCl3-MeOH extract of the bark of Aglaia crassinervia collected in Indonesia led to the isolation of aglaiaglabretols A (63) and C (64) [98], and derivative (65) of aglaiaglabretols A was found in the stems of Spathelia excelsa (Rutaceae) [99], and it exhibited larvicidal properties with LC50 of 4.8 µg/mL against yellow fever mosquito, Aedes aegypti.
Series of antitumor triterpene glucosides, named cumingianosides A (66, chemical structures 66–77 are shown in Figure 5, and their biological activity is shown in Table 5), D (67), E (68), M (69), J (70) and N (71) containing a 14,18-cycloapotirucallane-type skeleton were isolated from a cytotoxic fraction of the leaves of Dysoxylum cumingianum. The cytotoxic activity of cumingianosides showed that cumingianoside M (69) exhibited significant (<4 μM) cytotoxicity, especially against leukemia and melanoma cell lines [100,101].
A hexane extract of the wood of Dysoxylum muelleri has a yielded triterpenoid called dysoxin 3b (72), and dysoxylic acid A (73) was isolated from the hexane extract of the wood and bark of Dysoxylum pettigrewianum [102,103]. Dichapetalins are a small group of triterpenoids found primarily in the Dichapetalaceae and Euphorbiaceae. Thus, bioactive dichapetalins A (74), C (75), E (76), and G (77) were found in extracts of the roots of Dichapetalum madagascariense, and dichapetalin A (74) showed a strong and selective cytotoxic activity [104,105]. The aerial parts of Phyllanthus acutissima contained in CH2Cl2 extracts of several dichapetalin-type triterpenoids, acutissimatriterpenes A (78, chemical structures 78–89 are shown in Figure 6, and their biological activity is shown in Table 6), B (79), C (80), D (81), and E (82). The obtained compounds were demonstrated cytotoxic and anti-HIV-1 activities [106]. The 90% MeOH-soluble fraction of the leaves of Dysoxylum cumingianum led to the isolation of triterpenoids (84 and 85), which showed significant enhanced cytotoxicity in the presence of colchicine, indicating that they might have some MDR-reversal effect [107].
Natural ecdysteroids are found in marine invertebrates, insects, or plants, and they provide a remarkable resource of insect hormone analogues that influence insect development and metamorphosis and thus play a significant role in the chemical interactions between some marine invertebrates and insects [108]. Rare 14-deoxy-14,18-cyclo-20-hydroxyecdysone (86) was obtained by photochemical transformation of 20-hydroxyecdysone [109].
Cinanthrenol A (87), an estrogenic aromatic steroid containing a phenanthrene and a spiro[2,4]heptane systems has been isolated from a marine sponge Cinachyrella sp. [110].
Preschisanartanin (88) possessing a complex nortriterpenoid skeleton, was isolated from Schisandra chinensis, and demonstrated anti-HIV-1 activity with an EC50 value of 13.8 μg/mL [111,112,113], and lancolide A (89), highly oxygenated Schisandra nortriterpenoid was detected in the Schisandra lancifolia. This compound exhibited specific antiplatelet aggregation induced by platelet-activating factor [114].
A pentacyclic 3α,5α-cyclopregnane-type framework steroids represent a small group of natural lipids related to carbon-bridged steroids. These steroids have been found in both marine invertebrates and some terrestrial species. Two cytotoxic steroids, vladimuliecins A (90) and B (91), were isolated from the rhizome of Vladimiria muliensis. Both steroids demonstrated the cytotoxicity against cancer cell lines, including human leukemia cell (HL-60), human hepatoma cell (SMMC-7721), and human cervical carcinoma cell (HeLa) lines [115]. Chemical structures 90–102 are shown in Figure 7, and their biological activity is shown in Table 7.
An unusual steroid, named withawrightolide (92), was detected and isolated from the aerial parts of Datura wrightii (family Solanaceae). Isolated steroid showed antiproliferative activities against human glioblastoma (U251 and U87), head and neck squamous cell carcinoma (MDA-1986), and normal fetal lung fibroblast (MRC-5) cancer cell lines [116]. Glycoside, 6β-O-[β-d-glucopyranosyl-(1->6)-β-d-glucopyranosyl]-(20S,22R)-14α,17β,20-trihydroxy-18-acetoxy-3α,5α-cyclo-1-oxowitha-24-enolide, named physacoztolide F (93), was found in the CH2Cl2/MeOH extract of the aerial parts of Physalis coztomatl (family Solanaceae) [117]. Withanolide-type steroids named cilistols P (94), PM (95) and U (96) were isolated from the leaves of Solanum cilistum [118]. Psychotropic agent, 6β-hydroxy-3:5-cyclopregnan-20-one (97) also known as cyclopregnol was developed in the 1950s [119].
The physalins are a group of 13,14-seco-16,24-cycloergostane triterpenoids, which are produced by the Physalis species [120], and physalin S (98), isolated from the Physalis alkekengi var. francheti, had a 6β-hydroxy-3,5-cyclo arrangement, a common acid rearrangement product of 3-hydroxy-D5 steroids [121]. Steroidal compounds contained in Dracaena surculosa (family Agavaceae) led to the isolation of two 3,5-cyclospirostanol saponins (99 and 100) and 3,5-cyclofurostanol saponin (101) [122].
Ganolearic acid A (102), a 3,4-seco-hexanortriterpenoid featuring, a rare 3/5/6/5 tetracyclic system with anti-inflammatory activity, was obtained in trace amounts from Ganoderma cochlear [123].

3. Sterols and Triterpenoids with Cyclopropane Ring in the Side Chain

A cytotoxic steroid, aragusterol A (103, chemical structures 103–117 are shown in Figure 8, and their biological activity is shown in Table 8), which possessing potent antitumor activity, was isolated from the Okinawan sponge of the genus Xestospongia. The compound strongly inhibited the cell proliferation of KB, HeLaS3, P388, and LoVo cells in vitro, and showed potent in vivo antitumor activity toward P388 in mice and L1210 in mice [124]. Additionally, 26,27-cyclosterols aragusterols B (104), C (105), and D (106) have been identified and isolated from the Okinawan marine sponge of the genus Xestospongia [124,125]. Steroids, aragusterol A (103), petrosterol (107), orthoesterol B (108), and other cyclopropyl containing steroids (109 and 110) were isolated from the marine sponge Petrosia weinbergi [126]. In additional, 24,28-Methylenestigmast-5-en-3-ol (109) was detected in extracts of the marine chrysophyte alga, and pelagophtic alga Pulvinaria sp. [127,128].
Marine steroids having dimethylketal structure and named aragusteroketals A (111) and C (112) with cytotoxic activity have been isolated from an Okinawan marine sponge of Xestospongia sp. [125]. Many steroids have been found in the marine sponge Petrosia (Strongylophora) sp. collected from the Similan Island (Thailand). In addition to the already known steroids aragusterol A (103), petrosterol (107), and aragusteroketals A (111), compounds 113 and 114 were additionally identified [129]. Experimental data showed that aragusterol A (103) exhibited weak to moderate cytotoxicity, with the IC50 values in the range of 11–103 µM. The most potent was cytotoxic, with the IC50 values of 7.1 and 6.1 µM against HepG-2 and HeLa cell lines, respectively, while exhibiting moderate cytotoxicity with the IC50 values of 12.8, 37.9, 37.5, and 18.0 µM against the other four cancer cell lines, MOLT-3, A549, HuCCA-1, and MDA-MB-231, respectively. In addition, this compound showed broad-spectrum anti-proliferative activity against a panel of 14 human cancer cell lines (IC50 = 0.01–1.6 μM) [130]. A cyclopropane-containing hydroxy sterol, phrygiasterol (115), was isolated from starfish Hippasteria phrygiana [131], and an extract of the crown-of-thorns starfish Acanthaster planci contained cyclopropane-containing sterol (116) [132].
The steroid, (3β,4α,5α)-4-methylgorgostan-3-ol (117), is synthesized by marine algae and invertebrates, and it has been found in dinoflagellates Peridinium foliaceum and Glenodinium foliaceum, corky sea finger Briareum asbestinum, rough leather coral Sarcophyton glaucum, and soft coral Lobophytum sp. [133,134,135]. Steroidal saponins named poecillastrosides E (118) and G (119), an oxidized methyl at C-18, into a primary alcohol or a carboxylic acid, have been found in extracts of the Mediterranean deep-sea sponge Poecillastra compressa. Poecillastroside E (118, chemical structures 118–130 are shown in Figure 9, and their biological activity is shown in Table 9), bearing a carboxylic acid at C-18, showed antifungal activity against Aspergillus fumigatus [136].
A 5α,8α-epidioxy steroid (120) obtained from MeOH extracts of the sponge Tethya sp. possessing a cyclopropyl ring at C-24 of the sidechain [137]. Sterol ester, 24,26-cyclo-5α-cholest-(22E)-en-3β-4′,8′12′-trimetyltridecanoate (121), has been isolated from a deep-water marine sponge, Xestospongia sp. [138]. The steroid, (3β,24ξ,28ξ)-29-methyl-24,28-methylenestigmast-5-en-3-ol (122) was found in the sponge Pseudaxinyssa sp. [139], and another steroid, 25,28-cycloergost-5-en-3-ol, named sormosterol (123), was found in the sponge Lissodendoryx topsenti [140].
Three steroids, 5,6,11-trihydroxy-33-norgorgost-2-en-1-one (124), 1,3,11-trihydroxy-23-norgorgost-5-en-13-oic acid (125), and 3,11,24-Trihydroxy-9,11-secogorgost-5-en-9-one (126) were isolated from the soft corals Clavularia viridis, Sinularia dissecta, and Pseudopterogorgia sp., respectively [141,142,143]. Two steroids, klyflaccisteroids K (127) and L (128), were isolated from a soft coral Klyxum flaccidum. Klyflaccisteroid K is a rare 9,11-secosteroid with a 5,8-epidioxy-9-ene functional group, and klyflaccisteroid L has an unusual 11-norsteroid skeleton and is the first example of 11-oxasteroid isolated from natural sources. The compound (127) possessed moderate to weak cytotoxicity against multiple cancer cells [144].
A rare steroid named calysterol (129), the minor sterol component of the sponge Calyx niceaensis and Petrosia ficiformis, possessing the unique feature of a cyclopropene ring bridging C23,24 [145,146,147], and isocalysterol (130), was detected in the same sponge [148].
The dichloromethane-2-propanol (1:1) extract of the Indonesian marine sponge Strepsichordaia aliena yielded 20,24-bishomoscalarane sesterterpenes named honulactones A (131), B (132), E (133), F (134), and G (135). Honulactones A and B exhibited cytotoxicity against P-388, A-549, HT-29, and MEL-28 (at IC50 1 μg/mL) human tumor cell lines [149], and honu’enone (136) [150]. Chemical structures 131–142 are shown in Figure 10, and their biological activity is shown in Table 10.
It is known that human skin is responsible for the production of vitamin D. When exposed to ultraviolet radiation, which penetrates the epidermis and photolysis provitamin D3 to previtamin D3, and is photolyzed to 5,6-transvitamin D3 and two cyclopropane-containing derivatives of vitamin D3, suprasterol I (137) and suprasterol II (138). The resulting photolysis products are used for the treatment and prevention of psoriasis [151]. Mushrooms are a rich source of ergosterol, which is a precursor to vitamin D2. Wild-grown mushrooms have been shown to contain small amounts of vitamin D2. In addition, it is known that the content of vitamin D2 and its derivatives such as suprasterol I and II in cultivated mushrooms increases when exposed to artificial ultraviolet radiation. In addition, vitamin D2 and its derivatives suprasterol I and II have been found in mushrooms Agaricus bisporus, Pleurotus ostreatus, and Lentinula edodes, as well as several mushroom powders, Pleurotus eryngii, and Agaricus bisporus [152]. When studying the photosynthesis of vitamin D, using the modelling of non-adiabatic molecular dynamics, another cyclopropane-containing metabolite (139) was identified [153].
A limonoid named hortiolide D (140) was found in CH2Cl2 and MeOH extracts from the stem of Hortia oreadica [154]. The stem bark of Cedrelopsis gracilis (Ptaeroxylaceae) has yielded pentanortriterpenoid, cedkathryn A (141) [155]. Phragmalin-type limonoid, velutabularin F (142) was isolated from the stem bark of Chukrasia tabularis var. velutina [156]. Rare cytotoxic metabolite, 3-oxo-cycloart-22Z,24E-dien-26-oic acid (143) isolated from propolis collected in Myanmar, showed the most potent cytotoxicity against B16-BL6 cell, colon 26-L5, LLC A549, and HeLa HT -1080 cancer cell lines [157]. Chemical structures 143–148 are shown in Figure 11, and their biological activity is shown in Table 10.
Two cyclopropanic oleanane triterpenoids named donellanic acid B (144) and C (145) were obtained from Donella ubanguiensis, and its compounds showed cytotoxic and antimicrobial activities [158]. Rare triterpenoid saponins possessing the unique 15,27-cyclooleanane skeleton with different aromatic acyl moieties named verbesinosides A (146), C, (147) and F (148) were isolated from the leaves and flowers of Verbesina virginica [159].
It is known that carbon-bridged steroids are a rare group of synthetic lipids that are interesting, both in the beauty of the chemical structure, and show a wide range of biological activities. We have selected several carbon-bridged steroids containing a cyclopropane ring in the molecule that are not found in nature (149–164, chemical structures 149–164 are shown in Figure 12, and their biological activity is shown in Table 11). This is done to compare the biological activities of natural and synthetic steroids [18].
Thus, 6β-hydroxy-3α,5-cyclo-5α-androstan-17-one (149), and other analogues (150, 151 and 158) were synthesized as steroidal blood pressure-lowering hormones [160,161]. Cyclosteroids (152 and 153), which show an anabolic effect, were synthesized from 19-nor steroids, and would be of great interest for sports medicine as representatives of anabolic steroids [162,163], although other cyclosteroids (154–157) were synthesized as potential agents with antitumor properties [164,165,166].
A series of cyclopropane containing carbon-bridges steroids (159–164) have been synthesized in various laboratories, but the biological activity of these lipid molecules has not been determined [160,161,167,168].

4. Cyclobutane Containing Steroids and Triterpenoids

The cyclobutane unit is found as a basic structural element in a wide range of naturally occurring compounds in bacteria, fungi, plants, and marine invertebrates [18,19,169,170,171,172,173,174]. The chemistry and biochemistry of cyclobutanes is widely described in the scientific literature and is of great interest to chemists and pharmacologists, since many representatives of this class of compounds demonstrate a wide range of biological activities [18,19,73,175,176,177,178].
Unusual triterpenoids with an unprecedented skeleton named belamchinanes A (165), C (166), and D (167) were isolated from the seeds of Belamcanda chinensis. These belamchinanes feature a 4/6/6/6/5 polycyclic system, in which a four-membered carbocyclic ring bridges the C-1 and C-11 positions of a classical triterpenoid framework. Experimental studies showed that 165-167 dose-dependently protect age-related renal fibrosis in vitro [179]. Chemical structures 165–183 are shown in Figure 13, and their biological activity is shown in Table 12.
Three triterpenoids, with an unusual four-membered ring skeleton, produced by a bond across C-1 to C-11, ganosinensic acid A (168), B (169), and methyl ganosinensate A (170) were isolated from the fruiting body of Ganoderma sinense [180]. A protolimonoid named capulin (171), containing a four membered ring in its side chain, was isolated from stem barks of Capuronianthus mahafalensis (family Meliaceae), endemic to Madagascar [181]. Triterpenoid steroid, named solanoeclepin A (172), as a cyst nematode-hatching stimulant, was isolated from potato roots [182].
A rare limonoid named entanutilin A (173) was identified from the stem barks of Entandrophragma utile collected in Ghana (Africa). This limonoid possessing a cyclobutanyl ring, incorporating C-19 and a cycloheptanyl ring C, including C-30 [183], and the hexane extract of the bark of Entandrophragma delevoyi has yielded tetranortriterpenoid, delevoyin C (174) with similar skeleton [184].
Unusual two malabaricane type triterpenes, (14S,17S,20S,24R)-25-hydroxy-14,17-cyclo-20,24-epoxy-malabarican-3-one (175) и (14S,17S,20S,24R)-20,24,25-trihydroxy-14,17-cyclo-malabarican-3-one (176) were isolated from the oleoresin of the wounded trunk, Ailanthus malabarica [185]. Unusual triterpenoid bearing a monoterpene unit at C-16 (177) has been identified from Croton limae (Euphorbiaceae) [186].
Triterpenoids, 12α-acetoxy-13β,18β-cyclobutane-20,24-dimethyl-24-oxoscalar-16-en-25-ol (178, α-OH, and 179, β-OH) was detected in the marine sponge Phyllospongia papyracea, collected in Papua New Guinea [187]. Compound (179) has also been isolated from the marine Australian sponge Strepsichordaia lendenfeldi from Great Barrier Reef [188]. The dichloromethane fraction of the marine sponge Phyllospongia lamellosa, collected from the Red Sea, resulted in the isolation and characterization of two scalarane-type compounds, 12α-acetoxy-13β,18β-cyclobutane-24-methyl-24-oxoscalar-16-en-25β-ol (180, phyllospongin D) and 12a-acetoxy-13β,18β-cyclobutane-24-methyl-24-oxoscalar-16-en-25α-ol (181, phyllospongin E) [189]. The 12α-acetoxy-23,25-cyclo-16β,25-dihydroxy-20,24-dimethyl-24-oxoscalarane (182) was isolated from the Neo Guinean sponge Carteriospongia foliascens [190,191,192], and similar cyclobutanol-containing metabolite is the related ester, 12α-acetoxy-16β-(3′-hydroxy-butanoyloxy)-13β,18β-cyclobutan-20,24-dimethyl-24-oxosca-laran-25β-ol (183) was found in extracts of the Australian sponge Strepsichordaia lendenfeldi collected at the Great Barrier Reef [188].
Scalarane sesterterpenoids 20,24-bishomoscalaranes, carteriofenones Е (184), F (185), G (186), and H (187) were obtained from the marine sponge Carteriospongia foliascens, collected from the South China Sea. These compounds represented rare, naturally occurring scalaranes with a cyclobutane ring [193]. Chemical structures 184–196 are shown in Figure 14, and their biological activity is shown in Table 13.
The shrub Phyllanthus hainanensis, which is endemic to the island of Hainan province of China, has been used in traditional Chinese medicine for over 1000 years, has great pharmaceutical potential to treat diseases such as cancer and diabetes, and is also used to prevent, and treat, chronic hepatitis B virus infection [194,195]. Several highly modified triterpenoids, with a new carbon skeleton by incorporating two unique motifs of a 4,5- and a 5,5-spirocyclic systems and containing cyclopropane and cyclobutene fragments, named phainanoids A (188), B (189), C (190), D (191), E (192), F (193), G (194), H (195), and I (196), have been determined in the extracts of the Phyllanthus hainanensis [196,197]. All compounds exhibited exceptionally potent immunosuppressive activities in vitro against the proliferation of T and B lymphocytes. The most potent one, phainanoid F, showed activities against the proliferation of T cells with IC50 value of 2 nM (positive control CsA = 14 nM) and B cells with IC50 value of <1.6 nM (CsA = 352.8 nM), which is about 7 and 221 times as active as CsA, respectively.
Trichoside B (197, chemical structures 197–212 are shown in Figure 15, and their biological activity is shown in Table 14), withanolide glucoside, has been isolated from the n-butanolic fraction of the 75% methanolic extract of aerial parts of Tricholepis eburnea [198], and other unusual cyclobutene, containing secosteroid (198), was detected in oil from a pineal tropical plant Sida cordata (family Malvaceae), which is used to treat various diseases and ailments in many complementary and alternative medicine systems [199]. Studying the photoproducts obtained by photochemical processes of vitamin D, cyclobutane, containing vitamin D (199), was identified [200]. Toxisterol (200), as a minor transformation product of vitamin D2, has been found in various mushrooms [152].
A unique non-olefinic product containing a cyclobutane fragment (201) was obtained from 5,10-seco steroid containing Δ1(10)—and Δ5(6) -double bonds in the AB ring during photochemical transformation [201]. The steroid altrenogest, a progestin of the 19-nortestosterone group, which is widely used in veterinary medicine to suppress or synchronize estrus in horses and pigs, using photolysis experiments gives two photoproducts: (202) and (203) [202].
In the chemistry of steroid hormones, the modification of the skeleton of natural steroids is used to obtain compounds with a narrower and more targeted spectrum of biological action, which makes it possible for their practical application. Among the many types of such transformed steroids, compounds containing an additional carbocycle are of great interest [203,204,205].
Photochemical [2 + 2]-cycloaddition is a common method for the construction of pentacyclic steroids and, in contrast to dark reactions, allows the introduction of a cyclobutane moiety anywhere in the steroid molecule. Several pentacyclic steroids, with an additional four-membered cycle (204–212), have been synthesized using various photochemical methods, while the biological activity of synthetic steroids has not been studied [18,204,205].
As a potent inhibitor of aromatase [206,207], 2,19-Methano-androstenedione (213) was synthesized, and the steroid (214) has a 3,9-carbon bridge like that of the steroid, trichoside B [208]. Two 6,19-cycloprogesterones (215 and 216) were synthesized from 11,19-epithiopregnane, and the end products showed increased affinity for glucocorticoid receptors [209]. Steroids (218–221), with a cyclobutane moiety anywhere in the steroid molecule, have been synthesized with the aim of finding bioactive anticancer agents [160,167,168,210]. Chemical structures 213–221 are shown in Figure 16, and their biological activity is shown in Table 15.

5. Miscellaneous Cyclosteroids and Triterpenoids Derived from Marine and Terrestrial Sources

Two unique pentacyclic polyhydroxylated sterols (23S-16/S,23-cyclo-3α,6α,7φ8,23-tetrahydroxy-5α,14|9-cholestan-15-one, named xestobergsterol A (222), and 23S-16/3,23-cyclo-l/8,2/3,3α,6α,7|8,23-hexahydroxy-5α,14/3-cholestan-15-one, named xestobergsterol B (223)) have been found and identified from marine sponge Xestospongia bergquistia [211], and xestobergsterol C (224) was detected in the Okinawan marine sponge Ircinia sp. [212]. Chemical structures 222–235 are shown in Figure 17, and their biological activity is shown in Table 16.
Carbon-bridged steroids which were isolated from Jaborosa bergii presented a norbornane-type structure in ring D of the steroid nucleus (225–227), resulting from a carbon−carbon bond between C-15 and C-21. Jaborosalactols 18 (225) and 22 (227) have a 14α-hydroxy group while jaborosalactol 20 (226) contains 8,14-double bond [213].
The unusual cytotoxic steroid named gymnasterones A (228) was isolated from the microscopic fungus Gymnascella dankaliensis, associated with the sponge Halichondria japonica [214].
A steroidal alkaloid with a C-C linkage between C-16 and C-23, 3β-amino-16,23-cyclo-23β-hydroxy-5∝,16ξ,25β-22,26-epiminocholestan-17(20),22(N)-diene named solanocastrine (229) has been identified from extracts of the leaves of Solanum capsicastrum [215].
The spiranoid-γ-lactone steroid series have been found in lipid extracts in the genus Jaborosa. Interestingly, the first triterpenoid with a spiranoid-γ-lactone side chain was jaborosalactone P (230), which was collected over 30 years ago in extracts of Jaborosa odonelliana collected in Argentina [216]. Other related metabolites, such as jaborosalactone 12 (231), jaborosalactone 15 (232), and jaborosalactone 31 (233), were isolated from Jaborosa odonelliana, and jaborosalactone P was the major component in all samples collected in both spring and summer. In addition, jaborosalactone 31 (230) was found in extracts of all species studied, J. rotacea, J. odonelliana, J. runcinata, and J. araucana [217,218,219]. The triterpenes, named vannusals A (234) and B (235), with unusual skeletons, were obtained from the marine ciliate Euplotes vannus [220,221,222,223,224,225], and both compounds showed strong cytotoxic activity. Unusual 2,3-secofernane triterpenoid, alstonic acid B (236) has been isolated from Alsonia scholaris [226].
Several steroids (237–264), containing an additional 5- or 6-membered ring (s) in the steroid molecule, have been synthesized in various laboratories and demonstrate a wide range of biological activities [18,160,161,164,167,168,210,227,228,229,230,231,232], and their structures are shown in Figure 18 and Figure 19. Their pharmacological profile is presented in Table 16 and Table 17.
Carbon-bridged steroids, called taccalonolides (265–271), are a class of microtubule-stabilizing agents that exhibit selective cancer-fighting properties [233]. Tacca species are known to contain highly oxygenated ixocarpalactone-type steroids, with an additional ring formed by a carbon–carbon bond between C-16 and C-24, taccalonolide A being the first example of these compounds [120]. Chemical structures 265–272 are shown in Figure 20, and their biological activity is shown in Table 18. Carbon-bridged steroids, related to taccalonolide A, were isolated from Tacca plantaginea, Tacca subflaellata, and the Vietnamese plant Tacca paxiana [234,235,236,237,238]. Taccalonolides AF (272) and AJ (273), showing antiproliferative properties, were isolated from a fraction of an ethanol extract of T. plantaginea [239], and a carbon-bridged steroid, named physanolide A (274), with an unprecedented skeleton containing a seven-membered ring was isolated from Physalis angulate [240].
Trinor-cycloartane glycosides, 15α-hydroxy-16-dehydroxy-16(24)-en-foetidinol-3-O-β-d-xylopyranoside (275) and 28-hydroxy-foetidinol-3-O-β-d-xylopyranoside (276) were isolated from the butanol fraction of the roots of Cimicifuga foetida [241]. Chemical structures 273–276 are shown in Figure 21, and their biological activity is shown in Table 18.

6. Comparison of Biological Activities of Natural and Synthetic CBS and Triterpenoids

It is known that the chemical structure of both natural and synthetic molecules predetermines biological activity, which makes it possible to analyze the structure-activity relationships (SAR). Such a wise idea was first proposed by Brown and Fraser more than 150 years ago, in 1868 [242]; although, according to other sources, SAR originates from the field of toxicology, according to which Cros, in 1863, determined the relationship between the toxicity of primary aliphatic alcohols and their solubility in water [243]. More than 30 years later, Richet in 1893 [244], Meyer in 1899 [245], and Overton in 1901 [246] separately found a linear correlation between lipophilicity and biological effects. By 1935, Hammett [247,248] presented a method of accounting for the effect of substituents on reaction mechanisms using an equation that considered two parameters, namely the substituent constant and the reaction constant. Complementing Hammett’s model, Taft proposed, in 1956, an approach for separating the polar, steric, and resonance effects of substituents in aliphatic compounds [249]. Combining all previous developments, Hansch and Fujita laid out the mechanistic basis for the development of the QSAR method [250], and the linear Hansch equation, and Hammett’s electronic constants, are detailed in the book by Hansch and Leo published in 1995 [251].
Some well-known computer programs can, with some degree of reliability, estimate the pharmacological activity of organic molecules isolated from natural sources or synthesized compounds [252,253,254]. It is known that classical SAR methods are based on the analysis of (quantitative) structure-activity relationships for one or more biological activities, using organic compounds belonging to the same chemical series as the training set [255].
Computer program PASS, which has been continuously updating and improving for the past thirty years [256], is based on the analysis of a heterogeneous training set included information about more than 1.3 million known biologically active compounds with data on ca. 10,000 biological activities [257,258]. Chemical descriptors implemented in PASS, which reflect the peculiarities of ligand-target interactions, and the original realization of the Bayesian approach for elucidation of structure-activity relationships provides the average accuracy, and predictivity, for several thousand biological activities equal to about 96% [259,260]. In several comparative studies, it was shown that PASS outperforms, in predictivity, some other recently developed methods for the estimation of biological activity profiles [261,262,263]. Freely available via the Internet, PASS Online web-service [264] is used by more than thirty thousand researchers from almost a hundred countries to determine the most promising biological activities for both natural and synthetic compounds [258,259,260,265]. To reveal the hidden pharmacological potential of the natural substances, we are successfully using PASS for the past fifteen years [266,267,268,269,270].
In the current study, we obtained PASS predictions for about three hundred steroids and triterpenoids produced by different living organisms. PASS estimates are presented as Pa values, which correspond to the probability of belonging to a class of “actives” for each predicted biological activity. The higher the Pa value is, the higher the confidence that the experiment will confirm the predicted biological activity [260].

6.1. Antitumor Activity of Cyclopropane-Containing CBS and Triterpenoids

Analyzing the data obtained using the PASS of natural cyclopropane containing steroids and triterpenoids, it can be stated that, out of 102 lipid molecules (1–102, see Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6 and Figure 7 and Table 1, Table 2, Table 3, Table 4, Table 5, Table 6 and Table 7), only 27 showed antitumor activity with a reliability of more than 90 percent, with two steroidal glycosides, (25) and (41), showed antitumor activity with more than 99% confidence. Thus, PASS has confirmed the cytotoxic properties of these steroids, which have been determined experimentally. Other sterols and triterpenoids, with a cyclopropane ring, demonstrated weak to moderate antitumor activity with 70 to 90 percent confidence.
Among sterols and triterpenoids with a cyclopropane ring in the side chain, compounds were also found that demonstrate antitumor activity with a confidence level of more than 90 percent. These are steroids (103, 91.1%), (105, 93.4%), (112, 92.2%), (118, 96.3%), (119, 96.0%), and (120, 97.5%), which were isolated from the marine sponges Petrosia weinbergi, Xestospongia sp., Poecillastra compressa, and Tethya sp. A 3D graph of the predicted antitumor and related activities is shown in Figure 22.
Triterpenoid saponins, (146, 98.7%), (147, 98.0%), and (148, 96.9%), containing the cyclopropane ring at position 15:27, were isolated from the leaves and flowers extracts of Verbesina virginica, demonstrating the highest degree of confidence—more than 96%. A 3D graph of the predicted antitumor and related activities is shown in Figure 23.

6.2. Antitumor Activity of Cyclobutane-Containing CBS and Triterpenoids

Cyclobutane containing steroids and triterpenoids (165–221), isolated from natural sources as well as semi- and synthetic compounds, were also analyzed using PASS. Most of these lipid molecules showed moderate antitumor activity with 70 to 90 percent confidence, and only three, (197, 92.9%), (206, 90.8%), and (214, 90.9%), steroids showed antitumor activity with more than 90% confidence. A 3D graph of the predicted antitumor and related activities is shown in Figure 24.
The withanolide glucoside named trichoside B (197) is of type A-nor-sterols, and was isolated from the methanolic extract of aerial parts of Tricholepis eburnea, which is native to Afghanistan, compound (206) is a testosterone derivative dimer, and the steroid (214) contains a cyclobutane ring in ring A of the steroid.

6.3. Miscellaneous Cyclosteroids and Triterpenoids

Miscellaneous cyclosteroids and triterpenoids (222–276, see Figure 17, Figure 18, Figure 19, Figure 20 and Figure 21, and Table 16, Table 17 and Table 18) make up one-fifth of all compounds presented in this work. Two-thirds of lipid molecules demonstrate moderate activity, and seventeen compounds show strong antitumor activity with a confidence level of more than 90%, and the triterpenoid called taccalonolide Q (271) has the widest spectrum of biological activities among antitumor agents. A 3D graph of the predicted antitumor activities is shown in Figure 25. The data we obtained using PASS are supported by the data just published by Peng and colleagues, which shows a wide range of biological activities of taccalonolides [271].

7. Conclusions

This review focuses on a rare group of carbon-bridged steroids (CBS) and triterpenoids found in lipid extracts from various natural sources such as green, yellow-green, and red algae, sea sponges, soft corals, ascidians, starfish, and other marine invertebrates. These compounds are also found in amoebas, fungi, fungal endophytes, and plants. There are 276 steroids and triterpenoids presented in this review, which demonstrate a wide range of biological activities, but the most pronounced antitumor profile. This review summarizes biological activities as experimentally obtained and published in the open press, as well as by using the extensive PASS program. We must state that two-thirds of carbon-bridged steroids and triterpenoids show moderate activity levels with 70 to 90% confidence, and only one-third of these lipids show strong antitumor activity with more than 90% confidence. All lipid material presented is divided into four groups, which include: (a) CBS and triterpenoids containing a cyclopropane moiety; (b) CBS and triterpenoids with cyclopropane ring in the side chain; (c) CBS and triterpenoids containing a cyclobutane moiety; (d) CBS and triterpenoids containing cyclopentane, cyclohexane, or cycloheptane moieties. The most important conclusion shows that some CBS and triterpenoids from different lipid groups demonstrate selective action on different types of tumor cells, such as renal cancer, sarcoma, pancreatic cancer, prostate cancer, lymphocytic leukemia, myeloid leukemia, liver cancer, and genitourinary cancer with different degree of reliability.

Author Contributions

Conceptualization, V.M.D. and V.V.P.; methodology, V.M.D.; software, T.A.G.; validation, V.M.D. and V.V.P.; formal analysis, V.V.P.; investigation, V.M.D.; data curation, V.V.P.; writing—original draft preparation, V.M.D. and V.V.P.; writing—review and editing, V.M.D. and V.V.P.; visualization, V.V.P.; supervision, V.M.D.; project administration, V.M.D.; funding acquisition, V.V.P. and T.A.G. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Acknowledgments

The work (GTA and PVV) was done in the framework of the Russian Federation fundamental research program for the long-term period for 2021–2030.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Moss, G.P. The nomenclature of steroids. Eur. J. Biochem. 1989, 186, 429–458. [Google Scholar]
  2. Burger, A. Cyclopropane compounds of biological interest. Prog. Drug Res. 1971, 15, 227–270. [Google Scholar]
  3. Schoenheimer, R.; Evans, E.A., Jr. The chemistry of the steroids. Ann. Rev. Biochem. 1937, 6, 139–162. [Google Scholar] [CrossRef]
  4. Ruigh, W.L. The chemistry of the steroids. Ann. Rev. Biochem. 1945, 14, 225–262. [Google Scholar] [CrossRef]
  5. Bergmann, W.; McLean, M.J.; Lester, D. Contributions to the study of marine products. XIII. Sterols from various marine invertebrates. J. Org. Chem. 1943, 8, 271–282. [Google Scholar] [CrossRef]
  6. Koch, F.C. The steroids. Ann. Rev. Biochem. 1944, 13, 263–294. [Google Scholar] [CrossRef]
  7. Kokke, W.C.M.C.; Epsteing, S.; Lookll, S.A.; Raull, G.H.; Fenicall, W.; Djerassi, C. On the origin of terpenes in symbiotic associations between marine invertebrates and algae (Zooxanthellae). J. Biol. Chem. 1984, 259, 8168–8173. [Google Scholar] [CrossRef]
  8. Ermolenko, E.V.; Imbs, A.B.; Gloriozova, T.A.; Poroikov, V.V.; Dembitsky, V.M. Chemical diversity of soft coral steroids and their pharmacological activities. Mar. Drugs 2020, 18, 613. [Google Scholar] [CrossRef] [PubMed]
  9. Ciereszko, L.S. Sterol and diterpenoid production by zooxanthellae in coral reefs: A review. Biol. Oceanograph. 1989, 6, 363–374. [Google Scholar]
  10. Kanazawa, A. Sterols in marine invertebrates. Fisheries Sci. 2001, 67, 997–1007. [Google Scholar] [CrossRef] [Green Version]
  11. Sato, S.; Ikekawa, N.; Kanazawa, A.; Ando, T. Identification of 23-demethylacanthasterol in an asteroid, Acanthaster planci and its synthesis. Steroids 1980, 36, 65–71. [Google Scholar]
  12. Lopanik, N.B. Chemical defensive symbioses in the marine environment. Funct. Ecol. 2014, 28, 328–340. [Google Scholar] [CrossRef]
  13. Gascoigne, R.M.; Simes, J.J.H. The tetracyclic triterpenes. Quarterly Rev. Chem. Soc. 1955, 9, 328–361. [Google Scholar] [CrossRef]
  14. Henry, J.A. Chemistry of Cycloartenol and Cyclolaudenol. Ph.D. Theses, Glasgow University, Glasgow, UK, June 1954. [Google Scholar]
  15. Djerassi, C.; McCrindle, R. Terpenoids. Part LI. The isolation of some new cyclopropane-containing triterpenes from Spanish moss (Tillandsia usneoides, L.). J. Chem. Soc. 1962, 4034–4039. [Google Scholar] [CrossRef]
  16. De Meijere, A. Introduction:  Cyclopropanes and related rings. Chem. Rev. 2003, 103, 931–932. [Google Scholar] [CrossRef] [Green Version]
  17. Wessjohann, L.A.; Brandt, W.; Thiemann, T. Biosynthesis and metabolism of cyclopropane rings in natural compounds. Chem. Rev. 2003, 103, 1625–1648. [Google Scholar] [CrossRef]
  18. Dembitsky, V.M.; Gloriozova, T.A. Astonishing diversity of carbon-bridged steroids and their biological activities: A brief review. Eur. J. Biotechnol. Biosci. 2018, 6, 6–23. [Google Scholar]
  19. Fan, Y.Y.; Gao, X.H.; Yue, J.M. Attractive natural products with strained cyclopropane and/or cyclobutane ring systems. Sci. China Chem. 2016, 59, 1126–1141. [Google Scholar] [CrossRef]
  20. Wang, M.; Lu, P. Catalytic approaches to assemble cyclobutane motifs in natural product synthesis. Org. Chem. Front. 2018, 5, 254–259. [Google Scholar] [CrossRef]
  21. Namyslo, J.C.; Dieter, E. Kaufmann. The application of cyclobutane derivatives in organic synthesis. Chem. Rev. 2003, 103, 1485–1537. [Google Scholar] [CrossRef] [PubMed]
  22. Kilimnik, A.; Dembitsky, V.M. Anti-melanoma agents derived from fungal species. Mathews J. Pharm. Sci. 2016, 1, 002. [Google Scholar]
  23. Levitsky, D.O.; Gloriozova, T.A.; Poroikov, V.V.; Dembitsky, V.M. Naturally occurring isocyano/isothiocyanato compounds: Their pharmacological and SAR activities. Mathews J. Pharm. Sci. 2016, 1, 003. [Google Scholar]
  24. Kuklev, D.V.; Dembitsky, V.M. Chemistry, origin, antitumor and other activities of fungal homo-dimeric alkaloids. Mathews J. Pharm. Sci. 2016, 1, 004. [Google Scholar]
  25. Kilimnik, A.; Kuklev, D.V.; Dembitsky, V.M. Antitumor acetylenic lipids. Mathews J. Pharm. Sci. 2016, 1, 005. [Google Scholar]
  26. Dembitsky, V.M.; Gloriozova, T.A.; Poroikov, V.V. Pharmacological and predicted activities of natural azo compounds. Nat. Prod. Bioprospect. 2017, 6, 1–19. [Google Scholar]
  27. Dembitsky, V.M.; Gloriozova, T.A.; Poroikov, V.V. Biological activities of nitro steroids. J. Pharm. Res. Intern. 2017, 18, 1–19. [Google Scholar] [CrossRef]
  28. Dembitsky, V.M.; Gloriozova, T.A.; Poroikov, V.V. Pharmacological and predicted activities of natural azo compounds. Nat. Prod. Bioprospect. 2017, 7, 151–169. [Google Scholar]
  29. Dembitsky, V.M.; Gloriozova, T.A.; Poroikov, V.V. Pharmacological activities of epithio steroids. J. Pharm. Res. Intern. 2017, 18, 1–19. [Google Scholar] [CrossRef]
  30. Dembitsky, V.M.; Gloriozova, T.A.; Poroikov, V.V. Biological activities of organometalloid (As, At, B, Ge, Si, Se, Te) steroids. J. Appl. Pharm. Sci. 2017, 7, 184–202. [Google Scholar]
  31. Dembitsky, V.M.; Savidov, N.; Poroikov, V.V.; Gloriozova, T.A.; Imbs, A.B. Naturally occurring aromatic steroids and their biological activities. Appl. Microbiol. Biotech. 2018, 102, 4663–4674. [Google Scholar] [CrossRef] [PubMed]
  32. Dembitsky, V.M.; Gloriozova, T.A.; Savidov, N. Steroid phosphate esters and phosphonosteroids and their biological activities. Appl. Microbiol. Biotech. 2018, 102, 7679–7692. [Google Scholar] [CrossRef] [PubMed]
  33. Vil, V.A.; Gloriozova, T.A.; Poroikov, V.V.; Terent’ev, A.O.; Savidov, N.; Dembitsky, V.M. Peroxy steroids derived from plant and fungi and their biological activities. Appl. Microbiol. Biotech. 2018, 102, 7657–7667. [Google Scholar] [CrossRef] [PubMed]
  34. Dembitsky, V.M.; Gloriozova, T.A.; Poroikov, V.V. Naturally occurring marine α,β-epoxy steroids: Origin and biological activities. Vietnam. J. Chem. 2018, 56, 409–433. [Google Scholar] [CrossRef]
  35. Dembitsky, V.M.; Savidov, N.; Gloriozova, T.A. Sulphur containing steroids: Structures and biological activities. Vietnam. J. Chem. 2018, 56, 540–582. [Google Scholar] [CrossRef]
  36. Savidov, N.; Gloriozova, T.A.; Poroikov, V.V.; Dembitsky, V.M. Highly oxygenated isoprenoid lipids derived from fungi and fungal endophytes: Origin and biological activities. Steroids 2018, 140, 114–124. [Google Scholar] [CrossRef]
  37. Vil, V.; Terent’ev, A.O.; Al Quntar, A.A.A.; Gloriozova, T.A.; Savidov, N.; Dembitsky, V.M. Oxetane-containing metabolites: Origin, structures and biological activities. Appl. Microbiol. Biotech. 2019, 103, 2449–2467. [Google Scholar] [CrossRef] [PubMed]
  38. Vil, V.A.; Gloriozova, T.A.; Terent’ev, A.O.; Savidov, N.; Dembitsky, V.M. Hydroperoxides derived from marine sources: Origin and biological activities. Appl. Microbiol. Biotech. 2019, 103, 1627–1642. [Google Scholar] [CrossRef] [PubMed]
  39. Vil, V.A.; Gloriozova, T.A.; Poroikov, V.V.; Terent’ev, A.O.; Savidov, N.; Dembitsky, V.M. Naturally occurring of α, β-diepoxy-containing compounds: Origin, structures, and biological activities. Appl. Microbiol. Biotech. 2019, 103, 3249–3264. [Google Scholar] [CrossRef]
  40. Vil, V.A.; Terent’ev, A.O.; Savidov, N.; Gloriozova, T.A.; Poroikov, V.V.; Pounina, T.A.; Dembitsky, V.M. Hydroperoxy steroids and triterpenoids derived from plant and fungi: Origin, structures and biological activities. J. Steroid Biochem. Mol. Biol. 2019, 190, 76–87. [Google Scholar] [CrossRef]
  41. Vil, V.A.; Gloriozova, T.A.; Terent’ev, A.O.; Zhukova, N.V.; Dembitsky, V.M. Highly oxygenated isoprenoid lipids derived from terrestrial and aquatic sources: Origin, structures and biological activities. Vietnam. J. Chem. 2019, 57, 1–15. [Google Scholar] [CrossRef]
  42. Dembitsky, V.M. Antitumor and hepatoprotective activity of natural and synthetic neo steroids. Prog. Lipid Res. 2020, 79, 101048. [Google Scholar] [CrossRef]
  43. Dembitsky, V.M.; Dzhemileva, L.; Gloriozova, T.; D’yakonov, D. Natural and synthetic drugs used for the treatment of the dementia. Biochem. Biophys. Res. Commun. 2020, 524, 772–783. [Google Scholar] [CrossRef] [PubMed]
  44. Sikorsky, T.V.; Ermolenko, E.V.; Gloriozova, T.A.; Dembitsky, V.M. Mini Review: Anticancer activity of diterpenoid peroxides. Vietnam. J. Chem. 2020, 58, 273–280. [Google Scholar] [CrossRef]
  45. Dembitsky, V.M.; Gloriozova, T.A.; Poroikov, V.V. Pharmacological profile of natural and synthetic compounds with rigid adamantane-based scaffolds as potential agents for the treatment of neurodegenerative diseases. Biochem. Biophys. Res. Commun. 2020, 529, 1225–1241. [Google Scholar] [CrossRef] [PubMed]
  46. Dyshlovoy, S.A.; Honecker, H. Marine compounds and cancer: Updates 2020. Mar. Drugs 2020, 18, 643. [Google Scholar] [CrossRef]
  47. Mitome, H.; Shirato, N.; Hoshino, A.; Miyaoka, H.; Yamada, Y.; Yamada, Y.; Van Soest, R.W.M. New polyhydroxylated sterols stylisterols A–C and a novel 5, 19-cyclosterol hatomasterol from the Okinawan marine sponge Stylissa sp. Steroids 2005, 70, 63–70. [Google Scholar] [CrossRef]
  48. Zhang, W.-H.; Zhong, H.M.; Che, C.T. Cycloartanes from the red alga Galaxaura sp. J. Asian Nat. Prod. Res. 2005, 7, 59–65. [Google Scholar] [CrossRef]
  49. Goad, L.J.; Goodwin, T.W. Studies in phytosterol biosynthesis: Observations on the biosynthesis of fucosterol in the marine brown alga Fucus spiralis. Eur. J. Biochem. 1969, 7, 502–508. [Google Scholar] [CrossRef] [PubMed]
  50. Thyagarajan, S.; Johnson, A.J. Antidiabetes constituents, cycloartenol and 24-methyl-enecycloartanol, from Ficus krishnae. PLoS ONE 2020, 15, e0235221. [Google Scholar]
  51. Gibbons, G.F.; Goad, L.J.; Goodwin, T.W. The identification of 28-isofucosterol in the marine green algae Enteromorpha intestinalis and Ulva lactuca. Phytochemistry 1968, 7, 983–988. [Google Scholar] [CrossRef]
  52. Andinq, C.; Brandt, R.D.; Ourisson, G. Sterol biosynthesis in Euglena gracilis Z. Sterol precursors in light-grown and dark-grown Euglena gtacilis Z. Eur. J. Biochem. 1971, 24, 259–263. [Google Scholar] [CrossRef] [PubMed]
  53. Mercer, E.I.; Harries, W.B. The mechanism of alkylation at C-24 during clionasterol biosynthesis in Monodus subterraneus. Phytochemistry 1975, 14, 439–443. [Google Scholar] [CrossRef]
  54. Karunen, P.; Mikola, H.; Ekman, R. Separation and analysis of steryl and wax esters from Dicranum elongatum. Physiol. Plantarum 1980, 49, 351–353. [Google Scholar] [CrossRef]
  55. Miller, M.B.; Haubrich, B.A.; Wang, Q.; Snell, W.J.; Nes, W.D. Evolutionarily conserved 25(27) -olefin ergosterol biosynthesis pathway in the alga Chlamydomonas reinhardtii. J. Lipid Res. 2012, 53, 1636–1645. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  56. Tsai, L.B.; Patterson, G.W. The metabolism of cycloartenol, lanosterol, 24-methylene-cholesterol and fucosterol in Chlorella ellipsoidea. Phytochemistry 1976, 15, 1131–1133. [Google Scholar] [CrossRef]
  57. Nes, W.D.; Norton, R.A.; Crumley, F.G.; Madigan, S.J.; Katz, E.R. Sterol phylogenesis and algal evolution. Proc. Natl. Acad. Sci. USA 1990, 87, 7565–7569. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  58. Yoshida, M.; Ioki, M.; Matsuura, H.; Hashimoto, A.; Hashimoto, A.; Kaya, K.; Nobuyoshi, N. Diverse steroidogenic pathways in the marine alga Aurantiochytrium. J. Appl. Phycol. 2020, 32, 1631–1642. [Google Scholar] [CrossRef]
  59. Calegario, G.; Pollier, J.; Arendt, P.; de Oliveira, L.S.; Thompson, C.; Soares, A.R. Cloning and functional characterization of cycloartenol synthase from the red seaweed Laurencia dendroidea. PLoS ONE 2016, 11, e0165954. [Google Scholar] [CrossRef] [Green Version]
  60. Raederstorff, D.; Rohmer, M. Sterols of the unicellular algae Nematochrysopsis roscoffensis and Chrysotila lamellosa: Isolation of (24E)-24-n-propylidenecholesterol and 24-n-propylcholesterol. Phytochemistry 1984, 298, 631–634. [Google Scholar] [CrossRef]
  61. Raederstorff, D.; Rohmer, M. Sterol biosynthesis via cycloartenol and other biochemical features related to photosynthetic phyla in the amoebae Naegleria lovaniensis and Naegleria gruberi. Eur. J. Biochem. 1987, 164, 427–434. [Google Scholar] [CrossRef]
  62. Milankovic, M. Probing Sterol Biosynthesis Chokepoint Enzymes in Naegleria gruberi for Treatment of Amoeba Diseases. Ph.D. Thesis, Texas Tech University, Lubbock, TX, USA, May 2017. [Google Scholar]
  63. Raederstorff, D.; Rohmer, M. Sterol biosynthesis de novo via cycloartenol by the soil amoeba Acanthamoeba polyphaga. Biochem. J. 1985, 231, 609–615. [Google Scholar] [CrossRef] [Green Version]
  64. Puglisi, M.P.; Tan, L.T.; Jensen, P.R.; Fenical, W. Capisterones A and B from the tropical green alga Penicillus capitatus: Unexpected anti-fungal defences targeting the marine pathogen Lindra thallasiae. Tetrahedron 2004, 60, 7035–7039. [Google Scholar] [CrossRef]
  65. Patil, A.D.; Freyer, A.J.; Killmer, L.; Breen, A.; Johnson, R.K. A new cycloartanol sulfate from the green alga Tuemoya sp.: An inhibitor of VZV protease. Nat. Prod. Lett. 1997, 9, 209–215. [Google Scholar] [CrossRef]
  66. Govindan, M.; Abbas, S.A.; Schmitz, F.J.; Lee, R.H.; Papkoff, J.S.; Slate, D.L. New cycloartanol sulfates from the alga Tydemania expeditionis: Inhibitors of the protein tyrosine kinase pp60v-src. J. Nat. Prod. 1994, 57, 74–78. [Google Scholar] [CrossRef] [PubMed]
  67. Tran, T.V.A.; Nguyen, V.M.; Nguyen, T.A.N.; Nguyen, D.H.T.; Tran, D.H.; Bui, T.P.T.; Pham, V.T.; Nguyen, T.N. New triterpene sulfates from Vietnamese red alga Tricleocarpa fragilis and their α-glucosidase inhibitory activity. J. Asian Nat. Prod. Res. 2020. [Google Scholar] [CrossRef] [PubMed]
  68. Makarieva, T.N.; Stonik, V.A.; Kapustina, I.I.; Boguslavsky, V.M.; Dmitrenoik, A.S.; Kalinin, V.I.; Cordeiro, M.L.; Djerassi, C. Biosynthetic studies of marine lipids. 42. Biosynthesis of steroid and triterpenoid metabolites in the sea cucumber Eupentacta fraudatrix. Steroids 1993, 58, 508–517. [Google Scholar] [CrossRef]
  69. Wu, Z.H.; Liu, T.; Gu, C.X. Steroids and triterpenoids from the brown alga Kjellmaniella crassifolia. Chem. Nat. Compd. 2012, 48, 158–160. [Google Scholar] [CrossRef]
  70. Kikuchi, T.; Akihisa, T.; Tokuda, H.; Ukiya, M.; Watanabe, K.; Nishino, H. Cancer chemopreventive effects of cycloartane-type and related triterpenoids in in vitro and in vivo models. J. Nat. Prod. 2007, 70, 918–922. [Google Scholar] [CrossRef] [PubMed]
  71. Xinping, H.; Xiaobin, Z.; Liping, D.; Zhiwei, D.; Wenhan, L. Cycloartane triterpenes from marine green alga Cladophora fascicularis. Chin. J. Ocean. Limnol. 2006, 24, 443–448. [Google Scholar] [CrossRef]
  72. Wang, N.; Xu, G.; Fang, Y.; Yang, T.; Zhao, H.; Li, G. New flavanol and cycloartane glucosides from Landoltia punctata. Molecules 2014, 19, 6623–6634. [Google Scholar] [CrossRef] [Green Version]
  73. Li, C.; Wang, F.; Wu, X.; Cao, S. A new 24-homo-30-nor-cycloartane triterpenoid from a Hawaiian endophytic fungal strain. Tetrahedron Lett. 2020, 61, 151508. [Google Scholar] [CrossRef]
  74. Han, M.J.; Qin, D.; Ye, T.T.; Yan, X.; Wang, J.Q.; Duan, X.X. An endophytic fungus from Trichoderma harzianum SWUKD3.1610 that produces nigranoic acid and its analogues. Nat. Prod. Res. 2019, 33, 2079–2087. [Google Scholar] [CrossRef]
  75. Wang, L.; Qin, D.; Zhang, K.; Huang, Q.; Liu, S.; Han, M.J.; Dong, J.Y. Metabolites from the co-culture of nigranoic acid and Umbelopsis dimorpha SWUKD3.1410, an endophytic fungus from Kadsura angustifolia. Nat. Prod. Res. 2017, 31, 1414–1421. [Google Scholar] [CrossRef] [PubMed]
  76. Ondeyka, J.G.; Jayasuriya, H.; Herath, K.B.; Guan, Z.; Schulman, M. Steroidal and triterpenoidal fungal metabolites as ligands of liver X receptors. J. Antibiot. 2005, 58, 559–565. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  77. Akihisa, T.; Watanabe, K.; Yoneima, K.; Suzuki, T.; Kimura, Y. Biotransformation of cycloartane-type triterpenes by the fungus Glomerella fusarioides. J. Nat. Prod. 2006, 69, 604–607. [Google Scholar] [CrossRef] [PubMed]
  78. Berti, G.; Bottari, F.; Marsili, A.; Morelli, I.; Polvani, M.; Mandelbaum, A. 31-Norcycloartanol and cycloartanol from Polypodium vulgare. Tetrahedron Lett. 1967, 8, 125–130. [Google Scholar] [CrossRef]
  79. Aljubiri, S.M.; Mahgou, S.A.; Almansour, A.I.; Shaaban, M.; Shaker, K.H. Isolation of diverse bioactive compounds from Euphorbia balsamifera: Cytotoxicity and antibacterial activity studies. Saudi J. Biol. Sci. 2021, 28, 417–426. [Google Scholar] [CrossRef]
  80. Tavarez-Santamaría, Z.T.; Jacobo-Herrera, N.J.; Rocha-Zavaleta, L.; Zentella-Dehesa, A.; del Carmen Couder-García, B.; Martínez-Vázquez, M. A higher frequency administration of the nontoxic cycloartane-type triterpene argentatin A improved its anti-tumor activity. Molecules 2020, 25, 1780. [Google Scholar] [CrossRef] [Green Version]
  81. Shehla, N.; Li, B.; Cao, L.; Zhao, J.; Jian, Y.; Daniya, M. Xuetonglactones A–F: Highly oxidized lanostane and cycloartane triterpenoids from Kadsura heteroclita Roxb. Craib. Front. Chem. 2020, 7, 935. [Google Scholar] [CrossRef] [Green Version]
  82. Silva, C.J.; Djerassi, C. Isolation, stereochemistry, and biosynthesis of Šormosterol, a novel cyclopropane-containing sponge sterol. Coll. Czech. Chem. Comm. 1991, 56, 1093–1105. [Google Scholar] [CrossRef]
  83. Sun, H.; Liu, B.; Hu, J. Novel cycloartane triterpenoid from Cimicifuga foetida (Sheng ma) induces mitochondrial apoptosis via inhibiting Raf/MEK/ERK pathway and Akt phosphorylation in human breast carcinoma MCF-7 cells. Chin. Med. 2016, 11, 1. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. Qiu, F.; Liu, H.; Duan, H.; Chen, P.; Lu, S.J.; Yang, G.Z.; Lei, X.X. Isolation, structural elucidation of three new triterpenoids from the stems and leaves of Schisandra chinensis (Turcz) Baill. Molecules 2018, 23, 1624. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  85. Nian, Y.; Yang, J.; Liu, T.T.; Luo, Y.; Zhang, J.H.; Qiu, M.H. New anti-angiogenic leading structure discovered in the fruit of Cimicifuga yunnanensis. Scient. Rep. 2015, 5, 9026. [Google Scholar] [CrossRef] [Green Version]
  86. Yang, J.H.; Pu, J.X.; Wen, J.; Li, X.N.; He, F.; Su, J.; Li, Y.; Sun, H.D. Unusual cycloartane triterpenoids from Kadsura ananosma. Phytochemistry 2015, 109, 36–42. [Google Scholar] [CrossRef]
  87. Kuang, H.; Su, Y.; Yang, B.; Xia, Y.; Wang, Q.; Wang, Z.; Yu, Z. Three new cycloartenol triterpenoid saponins from the roots of Cimicifuga simplex Wormsk. Molecules 2011, 16, 4348–4357. [Google Scholar] [CrossRef] [PubMed]
  88. Sashidhara, K.V.; Singh, S.P.; Kant, R.; Maulik, P.R.; Sarkar, J.; Kanojiya, S.; Kumar, K.R. Cytotoxic cycloartane triterpene and rare isomeric bisclerodane diterpenes from the leaves of Polyalthia longifolia var. pendula. Bioorg. Med. Chem. Lett. 2020, 20, 5767–5771. [Google Scholar] [CrossRef]
  89. Wang, W.-H.; Nian, Y.; He, Y.-J.; Wan, L.-S.; Bao, N.-M.; Zhu, G.-L.; Wang, F.; Qiu, M.H. New cycloartane triterpenes from the aerial parts of Cimicifuga heracleifolia. Tetrahedron 2015, 71, 8018–8025. [Google Scholar] [CrossRef]
  90. Zheng, D.-J.; Zhou, J.; Liu, Q.; Yao, W.; Zhang, M.-Z.; Shao, B.-H.; Mo, J.-X.; Zhou, C.-X.; Gan, L.-S. Five new cycloartane triterpenoids from Beesia calthifolia. Fitoterapia 2015, 103, 283–288. [Google Scholar] [CrossRef]
  91. Wang, G.-W.; Lv, C.; Fang, X.; Tian, X.-H.; Ye, J.; Li, H.-L.; Shan, L.; Shen, Y.-H.; Zhang, W.-D. Eight pairs of epimeric triterpenoids involving a characteristic spiro-E/F ring from Abies faxoniana. J. Nat. Prod. 2015, 78, 50–60. [Google Scholar] [CrossRef]
  92. Gilardoni, G.; Chiriboga, X.; Vita Finzi, P.; Vidari, G. New 3,4-secocycloartane and 3,4-secodammarane triterpenes from the Ecuadorian plant Coussarea macrophylla. Chem. Biodiver. 2015, 12, 946–954. [Google Scholar] [CrossRef] [PubMed]
  93. Hitotsuyanagi, Y.; Ozeki, A.; Choo, C.Y.; Chan, K.L.; Itokawa, H.; Takeya, K. Malabanones A and B, novel nortriterpenoids from Ailanthus malabarica DC. Tetrahedron 2001, 57, 7477–7480. [Google Scholar] [CrossRef]
  94. Thongnest, S.; Boonsombat, J.; Prawat, H.; Mahidol, C.; Ruchirawat, S. Ailanthusins A-G and nor-lupane triterpenoids from Ailanthus triphysa. Phytochemistry 2017, 134, 98–105. [Google Scholar] [CrossRef]
  95. Ragasa, C.Y.; Torres, O.B.; Bernardo, L.O.; Mandia, E.H.; Don, M.J.; Shen, C.C. Glabretal-type triterpenoids from Dysoxylum mollissimum. Phytochem. Lett. 2013, 6, 514–518. [Google Scholar] [CrossRef]
  96. Choi, A.R.; Lee, I.K.; Woo, E.E.; Kwon, J.W.; Yun, B.S.; Park, H.R. New glabretal triterpenes from the immature fruits of Poncirus trifoliata and their selective cytotoxicity. Chem. Pharm. Bull. 2015, 63, 1065–1069. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  97. Kim, N.; Cho, K.W.; Hong, S.S.; Hwang, B.Y.; Chun, T.; Lee, D. Antiproliferative glabretal-type triterpenoids from the root bark of Dictamnus dasycarpus. Bioorg. Med. Chem. Lett. 2015, 25, 621–625. [Google Scholar] [CrossRef] [PubMed]
  98. Su, B.N.; Chai, H.; Mi, Q.; Riswan, S.; Kardono, L.B.S.; Afriastini, J.J.; Santarsiero, B.D.; Mesecar, A.D.; Farnsworth, N.R.; Cordell, G.A.; et al. Activity-guided isolation of cytotoxic constituents from the bark of Aglaia crassinervia collected in Indonesia. Bioorg. Med. Chem. 2006, 14, 960–972. [Google Scholar] [CrossRef] [PubMed]
  99. De Freitas, A.C.; da Paz Lima, M.; Ferreira, A.G.; Tadei, W.P.; da Silva Pinto, A.C. Constituintes quimicos do caule de Spathelia excelsa (Rutaceae) e atividade frente a Aedes aegypti. Quim. Nova 2009, 32, 2068–2072. [Google Scholar] [CrossRef]
  100. Kashiwada, Y.; Fujioka, T.; Chang, J.J.; Chen, I.S.; Mihashi, K.; Lee, K.H. Anti-tumor agents. 136. Cumingianosides A-F, potent antileukemic new triterpene glucosides, and cumindysosides A and B, trisnor- and tetranortriterpene glucosides with a 14,18-cycloapoeuphane-type skeleton from Dysoxylum cumingianum. J. Org. Chem. 1992, 57, 6946–6953. [Google Scholar] [CrossRef]
  101. Fujioka, T.; Sakurai, A.; Mihashi, K.; Kashiwada, Y.; Chen, I.S.; Lee, K.H. Antitumor agents. 168. Dysoxylum cumingianum. IV. The structures of cumingianosides G-O, new triterpene glucosides with a 14,18-cycloapotirucallane-type skeleton from Dysoxylum cumingianum, and their cytotoxicity against human cancer cell lines. Chem. Pharm. Bull. 1997, 45, 68–74. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  102. Mulholl, D.A.; Nair, J.J. Glabretal triterpenoids from Dysoxylum muelleri. Phytochemistry 1996, 42, 1667–1671. [Google Scholar] [CrossRef]
  103. Mulholl, D.A.; Nair, J.J. Triterpenoids from Dysoxylum pettigrewianum. Phytochemistry 1994, 37, 1409–1411. [Google Scholar] [CrossRef]
  104. Addae-Mensah, I.; Waibel, R.; Asunka, S.A.; Oppong, I.V.; Achenbach, H. The dichapetalins—A new class of triterpenoids. Phytochemistry 1996, 43, 649–656. [Google Scholar] [CrossRef]
  105. Osei-Safo, D.; Chama, M.A.; Addae-Mensah, I.; Waibel, R.; Asomaning, W.A.; Oppong, I.V. Dichapetalin M from Dichapetalum madagascariensis. Phytochem. Lett. 2008, 1, 147–150. [Google Scholar] [CrossRef]
  106. Tuchinda, P.; Kornsakulkarn, J.; Pohmakotr, M.; Kongsaeree, P.; Prabpai, S.; Yoosook, C.; Kasisit, J.; Napaswad, C.; Sophasan, S.; Reutrakul, V. Dichapetalin-Type Triterpenoids and lignans from the aerial parts of Phyllanthus acutissima. J. Nat. Prod. 2008, 71, 655–663. [Google Scholar] [CrossRef]
  107. Kurimoto, S.I. Chemical Studies on Meliaceous Plants (Dysoxylum cumingianum, Azadirachta indica) and a Lamiaceous Plant (Scutellaria coleifolia). Ph.D. Thesis, University of Tokushima, Tokushima, Japan, 2014. [Google Scholar]
  108. Lafont, R.; Dauphin-Villemant, C.; Warren, J.T.; Rees, H.H. Ecdysteroid Chemistry and Biochemistry. In Reference Module in Life Sciences; Roitberg, B.D., Ed.; Elsevier: New York, NY, USA, 2017; pp. 125–195. [Google Scholar]
  109. Harmatha, J.; Budesınsky, M.; Vokac, K. Photochemical transformation of 20-hydroxyecdysone: Production of monomeric and dimeric ecdysteroid analogues. Steroids 2002, 67, 127–135. [Google Scholar] [CrossRef]
  110. Machida, K.; Abe, T.; Arai, D.; Okamoto, M.; Shimizu, I.; de Voogd, N.J.; Fusetani, N.; Nakao, Y. Cinanthrenol A, an estrogenic steroid containing phenanthrene nucleus, from a marine sponge Cinachyrella sp. Org. Lett. 2014, 16, 1539–1541. [Google Scholar] [CrossRef]
  111. Huang, S.X.; Li, R.T.; Liu, J.P.; Lu, Y.; Chang, Y. Isolation and characterization of biogenetically related highly oxygenated nortriterpenoids from Schisandra chinensis. Org. Lett. 2007, 9, 2079–2082. [Google Scholar] [CrossRef]
  112. Hu, K.; Li, X.R.; Tang, J.W.; Li, X.N.; Puno, P.T. Structural determination of eleven new preschisanartane-type schinortriterpenoids from two Schisandra species and structural revision of preschisanartanin J using NMR computation method. Chin. J. Nat. Med. 2019, 17, 970–981. [Google Scholar] [CrossRef]
  113. Toda, F.; Garratt, P. Four-membered ring compounds containing bis(methylene)-cyclobutene or tetrakis(methylene)cyclobutane moieties. Benzocyclobutadiene, benzo-dicyclobutadiene, biphenylene, and related compounds. Chem. Rev. 1992, 92, 1685–1707. [Google Scholar] [CrossRef]
  114. Shi, Y.M.; Wang, X.B.; Li, X.N.; Luo, X.; Shen, Z.Y. Lancolides, antiplatelet aggregation nortriterpenoids with tricyclo[6.3.0.02,11]undecane-bridged system from Schisandra lancifolia. Org. Lett. 2013, 15, 5068–5071. [Google Scholar] [CrossRef]
  115. Chen, J.J.; Li, Z.M.; Gao, K.; Chang, J.; Yao, X.J. Vladimuliecins A and B: Cytotoxic pentacyclic pregnanols from Vladimiria muliensis. J. Nat. Prod. 2009, 72, 1128–1132. [Google Scholar] [CrossRef] [PubMed]
  116. Zhang, H.; Bazzill, J.; Gallagher, R.J.; Subramanian, C.; Grogan, P.T.; Day, V.W.; Kindscher, K.; Cohen, M.S.; Timmermann, B.N. Antiproliferative withanolides from Datura wrightii. J. Nat. Prod. 2013, 76, 445–449. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  117. Zhang, H.; Cao, C.M.; Gallagher, R.J.; Day, V.W.; Kindscher, K.; Timmermann, B.N. Withanolides from Physalis coztomatl. Phytochemistry 2015, 109, 147–153. [Google Scholar] [CrossRef] [PubMed]
  118. Zhu, X.H.; Ando, J.; Takagi, M.; Ikeda, T.; Yoshimitsu, A.; Nohara, T. Four novel withanolide-type steroids from the leaves of Solanum cilistum. Chem. Pharm. Bull. 2001, 49, 1440–1443. [Google Scholar] [CrossRef] [Green Version]
  119. Patel, D.K.; Petrow, V.; Stuart-Webb, I.A. 133. 6β-Hydroxy-3,5-cyclopregnan-20-one and some related compounds. J. Chem. Soc. 1957, 8, 665–668. [Google Scholar] [CrossRef]
  120. Misico, R.I.; Nicotra, V.E.; Oberti, J.C.; Barboza, G.; Gil, R.R.; Burton, G. Withanolides and related steroids. Prog. Chem. Org. Nat. Prod. 2011, 94. [Google Scholar] [CrossRef]
  121. Makino, B.; Kawai, M.; Kito, K.; Yamamura, H.; Butsugan, Y. New Physalins possessing an additional carbon-carbon bond from Physalis alkekengi var. francheti. Tetrahedron 1995, 51, 12529. [Google Scholar] [CrossRef]
  122. Yokosuka, A.; Mimaki, Y.; Sashida, Y. Four new 3,5-cyclosteroidal saponins from Dracaena surculosa. Chem. Pharm. Bull. 2002, 50, 992–995. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  123. Peng, X.-R.; Huang, Y.-J.; Lu, S.-Y.; Yang, J.; Qiu, M.-H. Ganolearic acid A, a hexanorlanostane triterpenoid with a 3/5/6/5-fused tetracyclic skeleton from Ganoderma cochlear. J. Org. Chem. 2018, 83, 13178. [Google Scholar] [CrossRef] [PubMed]
  124. Iguchi, K.; Fujita, M.; Nagaoka, H.; Mitome, H.; Yamada, Y. Aragusterol A: A potent antitumor marine steroid from the okinawan sponge of the genus, Xestospongia. Tetrahedron Lett. 1993, 34, 6277–6280. [Google Scholar] [CrossRef]
  125. Iguchi, K.; Shimura, H.; Taira, S.; Yokoo, C.; Matsumoto, K.; Yamada, Y. Aragusterol B and D, new 26,27-cyclosterols from the Okinawan marine sponge of the genus Xestospongia. J. Org. Chem. 1994, 59, 7499–7502. [Google Scholar] [CrossRef]
  126. Giner, J.-L.; Gunasekera, S.P.; Pomponi, S.A. Sterols of the marine sponge Petrosia weinbergi: Implications for the absolute configurations of the antiviral orthoesterols and weinbersterols. Steroids 1999, 64, 820–824. [Google Scholar] [CrossRef]
  127. Kokke, W.C.M.C.; Shoolery, J.N.; Fenical, W.; Djerassi, C. Biosynthetic studies of marine lipids. 4. Mechanism of side chain alkylation in E-24-propylidenecholesterol by a Chrysophyte alga. J. Org. Chem. 1984, 49, 3742–3752. [Google Scholar] [CrossRef]
  128. Giner, J.L.; Zimmerman, M.P.; Djerassi, C. Synthesis of (24R,28R)-and (24S, 28S)-24,28-methylene-5-stigmasten-3.beta.-ol and biosynthetic implications of cyclopropyl cleavage to 24-substituted cholesterols. J. Org. Chem. 1988, 53, 5895–5902. [Google Scholar] [CrossRef]
  129. Pailee, P.; Mahidol, C.; Ruchirawat, S.; Prachyawarakorn, V. Sterols from Thai marine sponge Petrosia (Strongylophora) sp. and their cytotoxicity. Mar. Drugs 2017, 15, 54. [Google Scholar] [CrossRef] [Green Version]
  130. Fukuoka, K.; Yamagishi, T.; Ichihara, T.; Nakaike, S.; Iguchi, K.; Yamada, Y. Mechanism of action of aragusterol a (YTA0040), a potent anti-tumor marine steroid targeting the G1 phase of the cell cycle. Int. J. Cancer 2000, 88, 810–819. [Google Scholar] [CrossRef]
  131. Levina, E.V.; Kalinovsky, A.I.; Andriyashchenko, P.V.; Dmitrenok, P.S.; Aminin, D.L.; Stonik, V.A. Phrygiasterol, a cytotoxic cyclopropane-containing polyhydroxysteroid, and related compounds from the Pacific starfish Hippasteria phrygiana. J. Nat. Prod. 2005, 68, 1541–1544. [Google Scholar] [CrossRef]
  132. Sheikh, Y.M.; Djerassi, C.; Tursch, B.M. Acansterol: A cyclopropane-containing marine sterol from Acanthaster planci. J. Chem. Soc. 1971, 2, 217–218. [Google Scholar] [CrossRef]
  133. Alam, M.; Martin, G.E.; Ray, S.M. Dinoflagellate sterols. 2. Isolation and structure of 4-methylgorgostanol from the dinoflagellate Glenodinium foliaceum. J. Org. Chem. 1979, 44, 4466–4467. [Google Scholar] [CrossRef]
  134. Withers, N.W.; Kokke, W.C.M.C.; Rohmer, M.; Fenical, W.H.; Djerassi, C. Isolation of sterols with cyclopropyl-containing side chains from the cultured marine alga Peridinium foliaceum. Tetrahedron Lett. 1979, 18, 3605–3609. [Google Scholar] [CrossRef]
  135. Kobayashi, M.; Ishizaka, T.; Mitsuhashi, H. Marine sterols X. Minor constituents of the sterols of the soft coral Sarcophyton glaucum. Steroids 1982, 40, 209–221. [Google Scholar] [CrossRef]
  136. Calabro, K.; Kalahroodi, E.L.; Rodrigues, D.; Díaz, C.; de la Cruz, M.; Cautain, B.; Laville, R.; Reyes, F.; Pérez, T.; Soussi, B.; et al. Poecillastrosides, steroidal saponins from the Mediterranean deep-sea sponge Poecillastra compressa (Bowerbank, 1866). Mar. Drugs 2017, 15, 199. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  137. Seo, Y.; Rho, J.; Cho, K.; Sim, C.J.; Shin, J. Isolation of epidioxysteroids from a sponge of the genus Tethya. Bull. Korean Chem. Soc. 1997, 18, 631–635. [Google Scholar]
  138. Gunasekera, S.P.; Cranick, S.; Pomponi, S.A. New sterol ester from a deep-water marine sponge, Xestospongia sp. J. Nat. Prod. 1991, 54, 1119–1122. [Google Scholar] [CrossRef]
  139. Ha, T.B.; Djerassi, C. Minor and trace sterols in marine invertebrates 52. isolation, structure elucidation and partial synthesis of 24-propyl-24, 28-methylenecholest-5-en-3β-ol. Tetrahedron Lett. 1985, 26, 4031–4034. [Google Scholar]
  140. Giner, J.-L.; Djerassi, C. Biosynthetic studies of marine lipids. 40. Generation of the cyclopropane ring of sormosterol. Acta Chem. Scand. 1992, 46, 678–679. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  141. Iwashima, M.; Nara, K.; Iguchi, K. New marine steroids, yonarasterols, isolated from the Okinawan soft coral, Clavularia viridis. Steroids 2000, 65, 130–137. [Google Scholar] [CrossRef]
  142. He, H.; Kulanthaivel, P.; Baker, B.J.; Kalter, K.; Darges, J.; Cofield, D.; Wolff, L.; Adams, L. New antiproliferative and antiinflammatory 9,11-secosterols from the gorgonian Pseudopterogorgia sp. Tetrahedron 1995, 51, 51–58. [Google Scholar] [CrossRef]
  143. Jagodzinska, B.M.; Trimmer, J.D.; Fenical, W.; Djerassi, C. Sterols in marine invertebrates. 51. Isolation and structure elucidation of C-18 functionalized sterols from the soft coral Sinularia dissecta. J. Org. Chem. 1985, 50, 2988–2992. [Google Scholar] [CrossRef]
  144. Tsai, Y.Y.; Huang, C.Y.; Tseng, W.R.; Chiang, P.L.; Hwang, T.L.; Sue, J.H.; Sunge, P.J.; Dai, C.F.; Sheu, J.H. Klyflaccisteroids K–M, bioactive steroidal derivatives from a soft coral Klyxum flaccidum. Bioorg. Med. Chem. Lett. 2017, 27, 1220–1224. [Google Scholar] [CrossRef]
  145. Minale, L.; Riccio, R.; Scalona, O.; Sodano, G.; Fattorusso, E.; Magno, S.; Mayol, L.; Santacroce, C. Metabolism in Porifera. VII. Conversion of [7,7-3H2]-fucosterol into calysterol by the sponge Calyx niceaensis. Experientia 1977, 33, 1550–1552. [Google Scholar] [CrossRef]
  146. Fatturosso, E.; Magno, S.; Mayol, L.; Santacrove, C.; Sioa, D. Calysterol: A C-29 cyclopropene-containing marine sterol from the sponge Calyx nicaensis. Tetrahedron 1975, 31, 1715–1716. [Google Scholar] [CrossRef]
  147. O’Connor, J.M.; Pu, L.; Chadha, R.K. Metallacycle annelation: Reaction of a metallacycle alpha-substituent and a vinylidene ligand to give a bicyclic metallalactone complex. J. Am. Chem. Soc. 1990, 112, 9627–9628. [Google Scholar] [CrossRef]
  148. Li, L.N.; Li, H.T.; Lang, R.W.; Itoh, T.; Sica, D.; Djerassi, C. Minor and trace sterols in marine invertebrates. 31. Isolation and structure elucidation of 23H-isocalysterol, a naturally occurring cyclopropene. Some comparative observations on the course of hydrogenolytic ring opening of steroidal cyclopropenes and cyclopropanes. J. Am. Chem. Soc. 1982, 104, 6726–6732. [Google Scholar]
  149. Jiménez, J.I.; Yoshida, W.; Scheuer, P.J.; Lobkovsky, E.; Clardy, J.; Kelly, M. Honulactones: New bishomoscalarane sesterterpenes from the Indonesian sponge Strepsichordaia aliena. J. Org. Chem. 2000, 65, 6837–6840. [Google Scholar] [CrossRef] [PubMed]
  150. Jiménez, J.I.; Yoshida, W.Y.; Scheuer, P.J.; Kelly, M. Scalarane-based sesterterpenes from an Indonesian sponge Strepsichordaia aliena. J. Nat. Prod. 2000, 63, 1388–1392. [Google Scholar] [CrossRef]
  151. Holick, M.F.; Smith, E.; Pincus, S. Skin as the site of vitamin D synthesis and target tissue for 1,25-dihydroxyvitamin D3 use of calcitriol (1,25-dihydroxyvitamin D3) for treatment of psoriasis. Arch. Dermatol. 1987, 123, 1677–1683. [Google Scholar] [CrossRef] [PubMed]
  152. Kalaras, M.D. Production of Ergocalciferol (vitamin D2) and Related Sterols in Mushrooms with Exposure to Pulsed Ultraviolet Light. Ph.D. Thesis, Pennsylvania State University, State College, PE, USA, January 2012. [Google Scholar]
  153. Tapavicza, E.; Meyera, A.M.; Furche, F. Unravelling the details of vitamin D photosynthesis by non-adiabatic molecular dynamics simulations. Phys. Chem. Chem. Phys. 2011, 13, 20986–20998. [Google Scholar] [CrossRef] [PubMed]
  154. Severino, V.G.P.; de Freitas, S.D.L.; Braga, P.A.C.; Forim, M.R.; da Silva, M.F.G.F.; Fernandes, J.B.; Vieira, P.C.; Venâncio, T. New limonoids from Hortia oreadica and unexpected coumarin from H. superba using chromatography over cleaning sephadex with sodium hypochlorite. Molecules 2014, 19, 12031–12047. [Google Scholar] [CrossRef] [Green Version]
  155. Mulholland, D.A.; McFarland, K.; Randrianarivelojosia, M.; Rabarison, H. Cedkathryns A and B, pentanortriterpenoids from Cedrelopsis gracilis (Ptaeroxylaceae). Phytochemistry 2004, 65, 2929–2934. [Google Scholar] [CrossRef] [PubMed]
  156. Luo, J.; Wang, J.S.; Luo, J.G.; Wang, X.B.; Kong, L.Y. Velutabularins A–J, phragmalin-type limonoids with novel cyclic moiety from Chukrasia tabularis var. velutina. Tetrahedron 2011, 67, 2942–2948. [Google Scholar] [CrossRef]
  157. Li, F.; Awale, S.; Tezuka, Y.; Kadota, S. Cytotoxic constituents of propolis from Myanmar and their structure–activity relationship. Biol. Pharm. Bull. 2009, 32, 2075–2078. [Google Scholar] [CrossRef] [Green Version]
  158. Djoumessi, A.V.B.; Sandjo, L.P.; Liermann, J.C.; Schollmeyer, D.; Vincent, V.K. Donellanic acids A–C: New cyclopropanic oleanane derivatives from Donella ubanguiensis (Sapotaceae). Tetrahedron 2012, 68, 4621–4627. [Google Scholar] [CrossRef]
  159. Xu, W.H.; Jacob, M.R.; Agarwal, A.K.; Clark, A.M.; Liang, Z.S.; Li, X.C. Verbesinosides A–F, 15,27-cyclooleanane saponins from the American native plant Verbesina virginica. J. Nat. Prod. 2009, 72, 1022–1027. [Google Scholar] [CrossRef] [Green Version]
  160. Huffman, M.N. 3,5-cyclo Steroids and the Production Thereof. U.S. Patent 2860147A, 11 November 1958. [Google Scholar]
  161. Gibb, B.C. The Synthesis and Structural Examination of 3a,5-cyclo-5a-Androstane Steroids. Ph.D. Thesis, University of Aberdeen, Aberdeen, UK, October 1992. [Google Scholar]
  162. Hutfman, M.N. 3, 5-Cyclo Steroids and the Production Thereof. U.S. Patent 2860147, 31 May 1951. [Google Scholar]
  163. Jeger, O. Cyclosteroid Compounds and Process for Their Manufacture. U.S. Patent 3014050, 19 December 1961. [Google Scholar]
  164. Yates, P.; Winnik, F.M. The synthesis of bridged steroids with a bicycle [2,2,1] heptane ring A system. Can. J. Chem. 1981, 59, 1641–1650. [Google Scholar] [CrossRef]
  165. Templeton, J.F.; Ling, Y.; Lin, W.; Majgier-Baranowska, H.; Marat, K. 19-Hydroxy-5β,19-cyclosteroids: Synthesis, isomerization and ring opening. J. Chem. Soc. Perkin Trans. 1 1997, 21, 1895–1904. [Google Scholar] [CrossRef]
  166. Bartlett, P.T.; Wingrove, A.S.; Owyang, R. Cycloaddition. VII. Competitive 1, 2-and 1, 4-addition to cis-fixed cyclic dienes. J. Am. Chem. Soc. 1968, 90, 6067–6070. [Google Scholar] [CrossRef]
  167. Ottow, E.; Schwede, W.; Halfbrodt, W.; Fritzemeier, K.-H.; Krattenmacher, R. Progestationally Active 19,11-Bridged 4-Estrenes. U.S. Patent 5703066A, 4 June 1997. [Google Scholar]
  168. Akhrem, A.A.; Titov, Y.A. Chemistry of 19-norsteroids. Russ. Chem. Rev. 1964, 33, 77–91. [Google Scholar] [CrossRef]
  169. Dembitsky, V.M. Bioactive cyclobutane-containing alkaloids. J. Nat. Med. 2008, 62, 1–33. [Google Scholar] [CrossRef]
  170. Sergeiko, A.; Poroikov, V.V.; Hanuš, L.O.; Dembitsky, V.M. Cyclobutane-containing alkaloids: Origin, synthesis, and biological activities. Open Med. Chem. J. 2008, 2, 26–37. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  171. Dembitsky, V.M. Chemistry and biodiversity of the biologically active natural glycosides. Chem. Biodiver. 2004, 1, 673–781. [Google Scholar] [CrossRef]
  172. Dembitsky, V.M.; Vil, V.A. Medicinal chemistry of stable and unsTable 1,2-dioxetanes: Origin, formation, and biological activities. Sci. Synthesis Knowl. Updates 2019, 3, 333–381. [Google Scholar]
  173. Dembitsky, V.M.; Dor, I.; Shkrob, I.; Aki, M. Branched alkanes and other apolar compounds produced by the cyanobacterium Microcoleus vaginatus from the Negev desert. Russ. J. Bioorg. Chem. 2001, 27, 110–119. [Google Scholar] [CrossRef]
  174. Dembitsky, V.M. Naturally occurring bioactive cyclobutane-containing (CBC) alkaloids in fungi, fungal endophytes, and plants. Phytomedicine 2014, 21, 1559–1581. [Google Scholar] [CrossRef] [PubMed]
  175. Zimmerman, N.B.; Vitousek, P.M. Fungal endophyte communities reflect environmental structuring across a Hawaiian landscape. Proc. Natl. Acad. Sci. USA 2012, 109, 13022–13027. [Google Scholar] [CrossRef] [Green Version]
  176. Li, J.; Gao, K.; Bian, M.; Ding, H. Recent advances in the total synthesis of cyclobutane-containing natural products. Org. Chem. Front. 2020, 7, 136–154. [Google Scholar] [CrossRef]
  177. Dembitsky, V.M.; Řezanka, T. Metabolites produced by nitrogen fixing Nostoc species. Folia Microbiol. 2005, 50, 363–391. [Google Scholar] [CrossRef]
  178. Řezanka, T.; Dembitsky, V.M. Metabolites produced by cyanobacteria belonging to several species of the family Nostocaceae. Folia Microbiol. 2006, 51, 159–182. [Google Scholar] [CrossRef] [PubMed]
  179. Song, Y.Y.; Miao, J.H.; Qin, F.Y.; Yan, Y.M.; Yang, J.; Cheng, Y.X. Belamchinanes A–D from Belamcanda chinensis: Triterpenoids with an unprecedented carbon skeleton and their activity against age-related renal fibrosis. Org. Lett. 2018, 20, 5506–5509. [Google Scholar] [CrossRef] [PubMed]
  180. Wang, C.F.; Liu, J.Q.; Yan, Y.X.; Chen, J.C.; Lu, Y.; Guo, Y.H.; Qiu, M.H. Three new triterpenoids containing four-membered ring from the fruiting body of Ganoderma sinense. Org. Lett. 2010, 12, 1656–1659. [Google Scholar] [CrossRef]
  181. Fossen, T.; Rasoanaivo, P.; Manjovelo, C.S.; Raharinjato, H.F.; Sviatlana Yahorava, S.; Yahorau, A.; Wikberg, J.E.S. A new protolimonoid from Capuronianthus mahafalensis. Fitoterapia 2012, 83, 901–906. [Google Scholar] [CrossRef] [PubMed]
  182. Schenk, H.; Driessen, R.A.J.; de Gelder, R.; Goubitz, K. Elucidation of the structure of solanoeclepin A, a natural hatching factor of potato and tomato cyst nematodes, by single-crystal x-ray diffraction. Croat. Chem. Acta 1999, 72, 593–606. [Google Scholar]
  183. Luo, J.; Tian, X.; Zhang, H.; Zhou, M.; Li, J.; Kong, L. Two rare limonoids from the stem barks of Entandrophragma utile. Tetrahedron Lett. 2016, 57, 5334–5337. [Google Scholar] [CrossRef]
  184. Mulholland, D.A.; Schwikkard, S.L.; Sandor, P.; Nuzillard, J.M. Delevoyin C, a tetranortriterpenoid from Entandrophragma delevoyi. Phytochemistry 2000, 53, 465–468. [Google Scholar] [CrossRef]
  185. Achanta, P.S.; Gattu, R.K.; Belvotagi, A.R.V.; Akkinepally, R.R.; Rao, A.; Achanta, V.N. New malabaricane triterpenes from the oleoresin of Ailanthus malabarica. Fitoterapia 2015, 100, 166–173. [Google Scholar] [CrossRef] [PubMed]
  186. Sousa, A.H.; Junior, J.N.S.; Guedes, M.L.S.; Braz-Filho, R.; Costa-Lotufo, L.V.; Araujo, A.J.; Silveira, E.R.; Lima, M.A.S. New terpenoids from Croton limae (Euphorbiaceae). J. Braz. Chem. Soc. 2015, 26, 1565–1572. [Google Scholar]
  187. Li, H.-J.; Amagata, T.; Tenny, K.; Crews, P. Additional scalarane sesterterpenes from the sponge Phyllospongia papyracea. J. Nat. Prod. 2007, 70, 802. [Google Scholar] [CrossRef]
  188. Jahn, T.; König, G.M.; Wright, A.D. Three new scalaranebased sesterterpenes from the tropical marine sponge Strepsichordaia lendenfeldi. J. Nat. Prod. 1999, 62, 375–377. [Google Scholar] [CrossRef]
  189. Hassan, M.H.A.; Rateb, M.E.; Hetta, M.; Abdelaziz, T.A.; Sleim, M.A.; Jaspars, M.; Mohammed, R. Scalarane sesterterpenes from the Egyptian Red Sea sponge Phyllospongia lamellosa. Tetrahedron 2015, 71, 577–583. [Google Scholar] [CrossRef]
  190. Braekman, J.C.; Daloze, D.; Kaisin, M.; Moussiaux, B. Ichthyotoxic sesterterpenoids from the neo guinean sponge Carteriospongia foliascens. Tetrahedron 1985, 41, 4603–4614. [Google Scholar] [CrossRef]
  191. Braekman, J.C.; Daloze, D.; Kaisin, M.; Moussiaux, B. Erratum: Ichthyotoxic sesterterpenoids from the neo guinean sponge Carteriospongia foliascens. Tetrahedron 1986, 42, 445–448. [Google Scholar]
  192. Braekman, J.C.; Daloze, D. Chemical defence in sponges. Pure Appl. Chem. 1986, 58, 357–364. [Google Scholar] [CrossRef] [Green Version]
  193. Cao, F.; Wu, Z.H.; Shao, C.L.; Pang, S.; Liang, X.Y.; de Voogd, N.J.; Wang, C.Y. Cytotoxic scalarane sesterterpenoids from the South China Sea sponge Carteriospongia foliascens. Org. Biomol. Chem. 2015, 13, 4016–4024. [Google Scholar] [CrossRef]
  194. Hoffmann, P.; Kathriarachchi, H.S.; Wurdack, K.J. A phylogenetic classification of phyllanthaceae. Kew Bulletin. 2006, 61, 37–53. [Google Scholar]
  195. Xia, Y.; Luo, H.; Liu, J.P.; Gluud, C. Phyllanthus species versus antiviral drugs for chronic hepatitis B virus infection. Cochrane Database Syst. Rev. 2013, 4, CD009004. [Google Scholar] [CrossRef] [Green Version]
  196. Fan, Y.Y.; Zhang, H.; Zhou, Y.; Liu, H.B.; Tang, W.; Zhou, B.; Zuo, J.P.; Yue, J.M. Phainanoids A–F, a new class of potent immunosuppressive triterpenoids with an unprecedented carbon skeleton from Phyllanthus hainanensis. J. Am. Chem. Soc. 2015, 137, 138–141. [Google Scholar] [CrossRef]
  197. Fan, Y.Y.; Gan, L.S.; Liu, H.C.; Li, H.; Xu, C.H.; Zuo, J.P.; Ding, J.; Yue, J.M. Phainanolide A, highly modified and oxygenated triterpenoid from Phyllanthus hainanensis. Org. Lett. 2017, 19, 4580–4583. [Google Scholar] [CrossRef]
  198. Maher, S.; Rasool, S.; Mehmood, R.; Perveen, S.; Tareen, R.B. Trichosides A and B, new withanolide glucosides from Tricholepis eburnean. Nat. Prod. Res. 2018, 32, 1–6. [Google Scholar] [CrossRef]
  199. Ganesh, M.; Mohankumar, M. Extraction and identification of bioactive components in Sida cordata (Burm.f.) using gas chromatography–mass spectrometry. J. Food Sci. Technol. 2017, 54, 3082–3091. [Google Scholar] [CrossRef]
  200. Jacobs, H.J.C. Photochemistry of conjugated trienes: Vitamin D revisited. Pure Appl. Chem. 1995, 67, 63–70. [Google Scholar] [CrossRef] [Green Version]
  201. Khripacha, V.A.; Zhabinskii, V.N.; Fando, G.P.; Kuchto, A.I.; Khripacha, N.B.; Groen, M.B.; van der Louw, J.; de Groot, A. A new type of steroids with a cyclobutane fragment in the AB-ring moiety. Steroids 2006, 71, 445–449. [Google Scholar] [CrossRef] [PubMed]
  202. Wammer, K.H.; Anderson, K.C.; Erickson, P.R.; Kliegman, S.; Moffatt, M.E.; Berg, S.M.; Heitzman, J.A. Environmental photochemistry of altrenogest: Photoisomerization to a bioactive product with increased environmental persistence via reversible photohydration. Environ. Sci. Technol. 2016, 50, 7480–7488. [Google Scholar] [CrossRef]
  203. Yan, P.; Zhou, Q.; Chen, J.; Lu, P. Controllable skeleton rearrangement of 3-substituted cyclobutanones under basic conditions. Chin. J. Chem. 2020, 38, 1103–1106. [Google Scholar] [CrossRef]
  204. Kamernitskii, A.V.; Ignatov, V.N.; Levina, I.S. Photochemical methods for the construction of an additional four-membered carbocycle in steroids. Russ. Chem. Rev. 1988, 57, 270–282. [Google Scholar] [CrossRef]
  205. Muller, E. Methoden der Organischen Chemie (Houben-Wcyl); G. Thieme Verlag: Stuttgart, Germany, 1971. [Google Scholar]
  206. Peet, N.P.; Johnston, J.O.; Burkhart, J.P.; Wright, C.L. A-ring bridged steroids as potent inhibitors of aromatase. J. Steroid Biochem. Mol. Biol. 1993, 44, 409–420. [Google Scholar] [CrossRef]
  207. Cross, A.D. Process for Conversion of 2,19-cyclo Steroids into 10 alpha-Steroids. U.S. Patent 3,139,426, 30 June 1964. [Google Scholar]
  208. Nagata, W.; Narisada, M.; Wakabashi, T.; Hayase, Y.; Murakami, M. Synthesis of bridged steroids. VI. B-norsteroids having a gibbane B-C-D ring system. Synthesis of 5-cyano-B-norsteroids via hydrocyanation. Chem. Pharm. Bull. 1971, 19, 1567–1581. [Google Scholar] [CrossRef] [Green Version]
  209. Di Chenna, P.H.; Veleiro, A.S.; Sonego, J.M.; Ceballos, N.R.; Garland, M.T.; Baggiod, R.F.; Burton, B. Synthesis of 6,19-cyclopregnanes. Constrained analogues of steroid hormones. Org. Biomol. Chem. 2007, 5, 2453–2457. [Google Scholar] [CrossRef]
  210. Johnston, J.O.; Wright, C.L.; Burkhart, J.P.; Peet, N.P. Biological characterization of A-ring steroids. J. Steroid Biochem. Mol. Biol. 1993, 44, 623–631. [Google Scholar] [CrossRef]
  211. Shoji, N.; Umeyama, A.; Shin, K.; Takeda, K.; Arihara, S.; Kobayashi, J.; Takei, M. Two unique pentacyclic steroids with cis C/D ring junction from Xestospongia bergquistia Fromont, powerful inhibitors of histamine release. J. Org. Chem. 1992, 57, 2996–2997. [Google Scholar] [CrossRef]
  212. Kobayashi, J.; Shinonaga, H.; Shigemori, H.; Umeyama, A.; Shoji, N.; Arihara, S. Xestobergsterol C, a new pentacyclic steroid from the Okinawan marine sponge Ircinia sp. and absolute stereochemistry of xestobergsterol A. J. Nat. Prod. 1995, 58, 312–318. [Google Scholar] [CrossRef]
  213. Nicotra, V.E.; Gil, R.R.; Vaccarini, C.; Oberti, J.C.; Burton, G. 15,21-Cyclowithanolides from Jaborosa bergii. J. Nat. Prod. 2003, 66, 1471–1479. [Google Scholar] [CrossRef]
  214. Amagata, T.; Minoura, K.; Numata, A. Gymnasterones, novel cytotoxic metabolites produced by a fungal strain from a sponge. Tetrahedron Lett. 1998, 39, 3773. [Google Scholar] [CrossRef]
  215. Chakravarty, A.K.; Pakrashi, S.C. Solanocastrine, a unique 16,23-cyclo-22,26-epiminocholestane from Solanum capsicastrum. Tetrahedron Lett. 1987, 28, 4753–4756. [Google Scholar] [CrossRef]
  216. Monteagudo, E.S.; Oberti, J.C.; Gros, E.G.; Burton, G. A spiranic withanolide from Jaborosa odonelliana. Phytochemistry 1990, 29, 933–939. [Google Scholar] [CrossRef]
  217. Cirigliano, A.M.; Veleiro, A.S.; Bonetto, G.M.; Oberti, J.C.; Burton, G. Spiranoid withanolides from Jaborosa runcinata and Jaborosa araucana. J. Nat. Prod. 1996, 59, 717–724. [Google Scholar] [CrossRef]
  218. Cirigliano, A.M.; Veleiro, A.S.; Oberti, J.C.; Burton, G. Spiranoid withanolides from Jaborosa odonelliana. J. Nat. Prod. 2002, 65, 1049–1052. [Google Scholar] [CrossRef] [PubMed]
  219. Cirigliano, A.M.; Misico, R.I. Spiranoid withanolides from Jaborosa odonelliana and Jaborosa runcinata. Z. Nat. B Chem. Sci. 2005, 60, 867–871. [Google Scholar] [CrossRef] [Green Version]
  220. Guella, G.; Dini, F.; Pietra, F. Metabolites with a novel C30 backbone from marine ciliates. Angew. Chem. Int. Ed. 1999, 38, 1134–1136. [Google Scholar] [CrossRef]
  221. Nicolau, K.C.; Zhang, H.; Ortiz, A.; Dagneau, P. Total synthesis of the originally assigned structure of vannusal B. Angew. Chem. Int. Ed. 2008, 47, 8605–8610. [Google Scholar] [CrossRef] [PubMed]
  222. Nicolau, K.C.; Zhang, H.; Ortiz, A. The true structure of the vannusals, part 1: Initial forays into suspected and intelligence gathering. Angew. Chem. Int. Ed. 2009, 48, 5642–5647. [Google Scholar] [CrossRef]
  223. Nicolau, K.C.; Ortiz, A.; Zhang, H. The true structures of the vannusals, part 2: Total synthesis and revised structure of vannusal B. Angew. Chem. Int. Ed. 2009, 48, 5648–5652. [Google Scholar] [CrossRef] [PubMed]
  224. Nicolau, K.C.; Ortiz, A.; Zhang, H.; Dagneau, P.; Lanver, A.; Jennings, M.P.; Arseniyadis, S.; Faraoni, R.; Lizos, D.E. Total synthesis and structural revision of vannusals A and B: Synthesis of the originally assigned structure of vannusal B. J. Am. Chem. Soc. 2010, 132, 7138–7152. [Google Scholar] [CrossRef] [Green Version]
  225. Nicolau, K.C.; Ortiz, A.; Zhang, H.; Guella, G. Total synthesis and structural revision of vannusals A and B: Synthesis of the true structures of vannusals A and B. J. Am. Chem. Soc. 2010, 132, 7153–7176. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  226. Wang, F.; Ren, F.-C.; Liu, J.-K. Alstonic acids A and B, unusual 2, 3-secofernane triterpenoids from Alstonia scholars. Phytochemistry 2009, 70, 650–654. [Google Scholar] [CrossRef] [PubMed]
  227. Yates, P.; Douglas, S.P.; Datta, S.K.; Sawyer, J.F. Bridged-ring steroids. V. The total synthesis of 1,4-methano steroids by a modified Torgov sequence. Can. J. Chem. 1988, 66, 2268–2278. [Google Scholar] [CrossRef]
  228. Yates, P.; Walliser, F.M. The reaction of steroid 2, 4-dienes with acetylenes. J. Chem. 1976, 54, 3508–3516. [Google Scholar] [CrossRef]
  229. Hanson, J.R. Steroids: Partial synthesis in medicinal chemistry. Nat. Prod. Rep. 2010, 27, 887–899. [Google Scholar] [CrossRef]
  230. Douglas, S.P.; Sawyer, J.F.; Yates, P. (±)-14[b]-Hydroxy-1[b], 4[b]-methano-5[b], 8[a],9[b]-androstane-7, 17-dione. Acta Crystal. 1987, C43, 1372–1375. [Google Scholar]
  231. Nagata, W.; Narisada, M.; Sugasawa, T.; Wakabayashi, T. Synthesis of bridged steroids. III. Cholestane derivatives having a bridged bicycle [2.2.2] octane ring system of the atisine type. Chem. Pharm. Bull. 1968, 16, 885–896. [Google Scholar] [CrossRef] [Green Version]
  232. Hanson, J.R.; Manickavasagar, R.; Thangavelu, V. The stereochemistry of oxidation of some B-norsteroids. J. Chem. Res. 1998, 4, 734–735. [Google Scholar] [CrossRef]
  233. Yee, S.S.; Du, L.; Risinger, A.L. Taccalonolide microtubule stabilizers. Prog. Chem. Org. Nat. Prod. 2020, 112, 183–206. [Google Scholar]
  234. Huang, Y.; Liu, J.-K.; Muhuhlbauer, A.; Henkel, T. Three novel taccalonolides from the tropical plant Tacca subflaellata. Helv. Chim. Acta 2002, 85, 2553–2558. [Google Scholar] [CrossRef]
  235. Shen, J.; Chen, Z.; Gao, Y. Taccalonolides from Tacca plantaginea. Phytochemistry 1996, 42, 891–899. [Google Scholar] [CrossRef]
  236. Chen, Z.-L.; Shen, J.-H.; Gao, Y.-S.; Wichtl, M. Five taccalonolides from Tacca plantaginea. Planta Med. 1997, 63, 40–46. [Google Scholar] [CrossRef]
  237. Yang, J.-Y.; Zhao, R.-H.; Chen, C.-X.; Ni, W.; Teng, F.; Hao, X.-J.; Liu, H.-Y. Taccalonolides W-Y, three new pentacyclic steroids from Tacca plantaginea. Helv. Chim. Acta 2008, 91, 1077–1081. [Google Scholar] [CrossRef]
  238. Muhlbauer, A.; Seip, S.; Nowak, A.; Tran, V.S. Five novel taccalonolides from the roots of the Vietnamese plant Tacca paxiana. Helv. Chim. Acta 2003, 86, 2065. [Google Scholar] [CrossRef]
  239. Li, J.; Risinger, A.L.; Peng, J.; Chen, Z.; Hu, L.; Mooberry, S.L. Potent Taccalonolides, AF and AJ, inform significant structure activity relationships and tubulin as the binding site of these microtubule stabilizers. J. Am. Chem. Soc. 2011, 133, 19064–19067. [Google Scholar] [CrossRef] [Green Version]
  240. Kuo, P.C.; Kuo, T.H.; Damu, A.G.; Su, C.R.; Lee, E.J.; Wu, T.S.; Shu, R.; Chen, C.M.; Bastow, K.F.; Chen, T.H.; et al. Physanolide A, a novel skeleton steroid, and other cytotoxic principles from Physalis angulate. Org. Lett. 2006, 8, 2953–2956. [Google Scholar] [CrossRef]
  241. Lu, L.; Chen, J.; Nian, Y.; Sun, Y.; Qiu, M. Trinor-cycloartane glycosides from the rhizomes of Cimicifuga foetida. Molecules 2009, 14, 1578–1584. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  242. Brown, A.C.; Fraser, T.R. The connection of chemical constitution and physiological action. Trans. Roy. Soc. Edinburg 1868, 25, 224–242. [Google Scholar]
  243. Cros, A.F.A. Action de l’Alcohol Amylique Sur l’Organisme. Ph.D. Thesis, University of Strasbourg, Strasbourg, France, 1863. [Google Scholar]
  244. Richet, M.C. Note sur le rapport entre la toxicité et les propriétes physiques des corps. Compt. Rend. Soc. Biol. 1893, 45, 775–776. [Google Scholar]
  245. Meyer, H. Zur Theorie der AIkoholnarkose. Arch. Exp. Path. Pharm. 1899, 42, 109–118. [Google Scholar] [CrossRef]
  246. Overton, C.E. Studien über die Narkose; Fischer: Jena, Germany, 1901. [Google Scholar]
  247. Hammett, L.P. Some relations between reaction rates and equilibrium constants. Chem. Rev. 1935, 17, 125–136. [Google Scholar] [CrossRef]
  248. Hammett, L.P. The effect of structure upon the reactions of organic compounds. Benzene derivatives. J. Am. Chem. Soc. 1937, 59, 96–103. [Google Scholar] [CrossRef]
  249. Taft, R.W. Separation of polar, steric and resonance effects in reactivity. In Steric Effects in Organic Chemistry; Newman, M.S., Ed.; Wiley: Hoboken, NJ, USA, 1956; pp. 556–675. [Google Scholar]
  250. Hansch, C.; Fujita, T. p-σ-π Analysis. A method for the correlation of biological activity and chemical structure. J. Am. Chem. Soc. 1964, 86, 1616–1626. [Google Scholar] [CrossRef]
  251. Hansch, C.; Leo, A. Exploring QSAR; American Chemical Society: Washington, DC, USA, 1995. [Google Scholar]
  252. Sliwoski, G.; Kothiwale, S.; Meiler, J.; Lowe, E.W., Jr. Computational methods in drug discovery. Pharm. Rev. 2014, 66, 334–395. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  253. Leelananda, S.P.; Lindert, S. Computational methods in drug discovery. Beilstein J. Org. Chem. 2016, 12, 2694–2718. [Google Scholar] [CrossRef] [Green Version]
  254. Kokh, D.B.; Amaral, M.; Bomke, J.; Grädler, U.; Musil, D. Estimation of drug-target residence times by τ-random acceleration molecular dynamics simulations. J. Chem. Theor. Comput. 2018, 14, 3859–3869. [Google Scholar] [CrossRef]
  255. Cherkasov, A.M.; Muratov, E.N.; Fourches, D.; Varnek, A.; Baskin, I.I.; Cronin, M.; Dearden, J. QSAR modeling: Where have you been? Where are you going to? J. Med. Chem. 2014, 57, 4977–5010. [Google Scholar] [CrossRef] [Green Version]
  256. Burov, Y.V.; Poroikov, V.V.; Korolchenko, L.V. National system for registration and biological testing of chemical compounds: Facilities for new drugs search. Bull. Natl. Center Biol. Act. Comp. 1990, 1, 4–25. [Google Scholar]
  257. Muratov, E.N.; Bajorath, J.; Sheridan, R.P.; Tetko, I.; Filimonov, D.; Poroikov, V.; Oprea, T. QSAR without borders. Chem. Soc. Rev. 2020, 49, 3525–3564. [Google Scholar] [CrossRef]
  258. Poroikov, V.V.; Filimonov, D.A.; Gloriozova, T.A.; Lagunin, A.A.; Druzhilovskiy, D.S.; Rudik, A.V. Computer-aided prediction of biological activity spectra for organic compounds: The possibilities and limitations. Russ. Chem. Bull. 2019, 68, 2143–2154. [Google Scholar] [CrossRef]
  259. Filimonov, D.A.; Druzhilovskiy, D.S.; Lagunin, A.A.; Gloriozova, T.A.; Rudik, A.V.; Dmitriev, A.V.; Pogodin, P.V.; Poroikov, V.V. Computer-aided prediction of biological activity spectra for chemical compounds: Opportunities and limitations. Biom. Chem. Res. Method 2018, 1, e00004. [Google Scholar] [CrossRef] [Green Version]
  260. Filimonov, D.A.; Lagunin, A.A.; Gloriozova, T.A.; Rudik, A.V.; Druzhilovskiy, D.S.; Pogodin, P.V.; Poroikov, V.V. Prediction of the biological activity spectra of organic compounds using the PASS online web resource. Chem. Heterocycl. Compd. 2014, 50, 444–457. [Google Scholar] [CrossRef]
  261. Anusevicius, K.; Mickevicius, V.; Stasevych, M.; Zvarych, V.; Komarovska-Porokhnyavets, O.; Novikov, V.; Tarasova, O.; Gloriozova, T.; Poroikov, V. Design, synthesis, in vitro antimicrobial activity evaluation and computational studies of new N-(4-iodophenyl)—Alanine derivatives. Res. Chem. Intermed. 2015, 41, 7517–7540. [Google Scholar] [CrossRef]
  262. Druzhilovskiy, D.S.; Rudik, A.V.; Filimonov, D.A.; Lagunin, A.A.; Gloriozova, T.A.; Poroikov, V.V. Online resources for the prediction of biological activity of organic compounds. Rus. Chem. Bull. 2016, 65, 384–393. [Google Scholar] [CrossRef]
  263. Murtazalieva, K.A.; Druzhilovskiy, D.S.; Goel, R.K.; Sastry, G.N.; Poroikov, V.V. How good are publicly available web services that predict bioactivity profiles for drug repurposing? SAR QSAR Environ. Res. 2017, 28, 843–862. [Google Scholar] [CrossRef]
  264. PASS Online URL. Available online: http://www.way2drug.com/passonline/ (accessed on 29 April 2021).
  265. Lagunin, A.A.; Goel, R.K.; Gawande, D.Y.; Priynka, P.; Gloriozova, T.A.; Dmitriev, A.V.; Ivanov, S.M.; Rudik, A.V.; Konova, V.I.; Pogodin, P.V. Chemo- and bioinformatics resources for in silico drug discovery from medicinal plants beyond their traditional use: A critical review. Nat. Prod. Rep. 2014, 31, 1585–1611. [Google Scholar] [CrossRef]
  266. Goel, R.K.; Poroikov, V.; Gawande, D.; Lagunin, A.; Randhawa, P.; Mishra, A. Revealing medicinal plants useful for comprehensive management of epilepsy and associated co-morbidities through in silico mining of their phytochemical diversity. Planta Med. 2015, 81, 495–506. [Google Scholar]
  267. Dembitsky, V.M.; Gloriozova, T.A.; Poroikov, V.V. Naturally occurring plant isoquinoline N-oxide alkaloids: Their pharmacological and SAR activities. Phytomedicine 2015, 22, 183–202. [Google Scholar] [CrossRef] [PubMed]
  268. Gawande, D.Y.; Druzhilovsky, D.; Gupta, R.C.; Poroikov, V.; Goel, R.K. Anticonvulsant activity and acute neurotoxic profile of Achyranthes aspera Linn. J. Ethnopharmacol. 2017, 202, 97–102. [Google Scholar] [CrossRef] [PubMed]
  269. Pounina, T.A.; Gloriozova, T.A.; Savidov, N.; Dembitsky, V.M. Sulfated and sulfur-containing steroids and their pharmacological profile. Mar. Drugs 2021, 19, 240. [Google Scholar] [CrossRef] [PubMed]
  270. Lagunin, A.; Povydysh, M.; Ivkin, D.; Luzhanin, V.; Krasnova, M.; Okovityi, S.; Nosov, A.; Titova, M.; Tomilova, S.; Filimonov, D.; et al. Antihypoxic action of Panax Japonicus, Tribulus Terrestris and Dioscorea Deltoidea cell cultures: In silico and animal studies. Mol. Inform. 2020, 39, 2000093. [Google Scholar] [CrossRef] [PubMed]
  271. Chen, X.; Winstead, A.; Yu, H.; Peng, J. Taccalonolides: A novel class of microtubule-stabilizing anticancer agents. Cancers 2021, 13, 920. [Google Scholar] [CrossRef] [PubMed]
Marinedrugs 19 00324 g001 550
Figure 1. Bioactive steroids containing an additional 3-membered ring in molecule.
Figure 1. Bioactive steroids containing an additional 3-membered ring in molecule.
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Figure 2. Bioactive steroids containing an additional 3-membered ring in the steroid molecule.
Figure 2. Bioactive steroids containing an additional 3-membered ring in the steroid molecule.
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Figure 3. Bioactive steroids containing an additional 3-membered ring in the steroid molecule.
Figure 3. Bioactive steroids containing an additional 3-membered ring in the steroid molecule.
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Figure 4. Bioactive steroids containing an additional 3-membered ring in the steroid molecule.
Figure 4. Bioactive steroids containing an additional 3-membered ring in the steroid molecule.
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Figure 5. Bioactive steroids containing an additional 3-membered ring in the steroid molecule.
Figure 5. Bioactive steroids containing an additional 3-membered ring in the steroid molecule.
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Figure 6. Bioactive cyclopropane-containing steroids and meroterpenoids.
Figure 6. Bioactive cyclopropane-containing steroids and meroterpenoids.
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Figure 7. Bioactive cyclopropane-containing steroids.
Figure 7. Bioactive cyclopropane-containing steroids.
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Figure 8. Bioactive sterols and triterpenoids with cyclopropane ring in the side chain.
Figure 8. Bioactive sterols and triterpenoids with cyclopropane ring in the side chain.
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Figure 9. Bioactive sterols and triterpenoids with cyclopropane ring in the side chain.
Figure 9. Bioactive sterols and triterpenoids with cyclopropane ring in the side chain.
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Figure 10. Bioactive cyclopropane-containing steroids and triterpenoids.
Figure 10. Bioactive cyclopropane-containing steroids and triterpenoids.
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Figure 11. Bioactive steroids containing an additional 3-membered ring in the steroid molecule.
Figure 11. Bioactive steroids containing an additional 3-membered ring in the steroid molecule.
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Figure 12. Bioactive synthetic cyclopropane-containing steroids.
Figure 12. Bioactive synthetic cyclopropane-containing steroids.
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Figure 13. Bioactive cyclobutane-containing steroids and triterpenoids.
Figure 13. Bioactive cyclobutane-containing steroids and triterpenoids.
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Figure 14. Bioactive cyclobutane-containing steroids and triterpenoids.
Figure 14. Bioactive cyclobutane-containing steroids and triterpenoids.
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Figure 15. Bioactive natural and synthetic cyclobutane-containing steroids and triterpenoids.
Figure 15. Bioactive natural and synthetic cyclobutane-containing steroids and triterpenoids.
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Figure 16. Bioactive synthetic steroids containing an additional 4-membered ring in the steroid molecule.
Figure 16. Bioactive synthetic steroids containing an additional 4-membered ring in the steroid molecule.
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Figure 17. Bioactive steroids containing an additional 5- or 6-membered ring in molecule.
Figure 17. Bioactive steroids containing an additional 5- or 6-membered ring in molecule.
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Figure 18. Bioactive cyclopentane- and cyclohexane-containing steroids.
Figure 18. Bioactive cyclopentane- and cyclohexane-containing steroids.
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Figure 19. Bioactive synthethic steroids containing an additional 5- or 6-membered ring in molecule.
Figure 19. Bioactive synthethic steroids containing an additional 5- or 6-membered ring in molecule.
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Figure 20. Bioactive steroids containing additional 6-membered ring in molecule.
Figure 20. Bioactive steroids containing additional 6-membered ring in molecule.
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Figure 21. Bioactive steroids containing additional 6- or 7-membered ring in molecule.
Figure 21. Bioactive steroids containing additional 6- or 7-membered ring in molecule.
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Figure 22. The 3D graph (X and Y views) shows the predicted and calculated antitumor activity of carbon- bridged steroids (CBS) with a cyclopropane ring in the side chain (compound numbers: 103, 105, 112, 118, 119 and 120) showing the highest degree of confidence, more than 91%. These steroids derived from marine sponges Petrosia weinbergi, Xestospongia sp., Poecillastra compressa, and Tethya sp., and can be used in clinical medicine as potential agents with strong antitumor activity.
Figure 22. The 3D graph (X and Y views) shows the predicted and calculated antitumor activity of carbon- bridged steroids (CBS) with a cyclopropane ring in the side chain (compound numbers: 103, 105, 112, 118, 119 and 120) showing the highest degree of confidence, more than 91%. These steroids derived from marine sponges Petrosia weinbergi, Xestospongia sp., Poecillastra compressa, and Tethya sp., and can be used in clinical medicine as potential agents with strong antitumor activity.
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Figure 23. The 3D graph shows the predicted and calculated antitumor and related activities of cyclopropane-containing triterpenoid saponins (compound numbers: 146, 147, and 148) showing the highest degree of confidence, more than 96%, which were isolated from the leaves and flowers extracts of Verbesina virginica, and can be used in clinical medicine as potential agents with strong antitumor activity.
Figure 23. The 3D graph shows the predicted and calculated antitumor and related activities of cyclopropane-containing triterpenoid saponins (compound numbers: 146, 147, and 148) showing the highest degree of confidence, more than 96%, which were isolated from the leaves and flowers extracts of Verbesina virginica, and can be used in clinical medicine as potential agents with strong antitumor activity.
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Figure 24. The 3D graph shows the predicted and calculated antitumor and related activities of cyclobutane-containing steroids (compound numbers: 197, 206, and 214) showing the highest degree of confidence, more than 90%.
Figure 24. The 3D graph shows the predicted and calculated antitumor and related activities of cyclobutane-containing steroids (compound numbers: 197, 206, and 214) showing the highest degree of confidence, more than 90%.
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Figure 25. The 3D graph shows the predicted and calculated pharmacological activities of taccalonolide Q (271). Taccalonolide Q, similar to other taccalonolides, is a class of highly acetoxylated pentacyclic steroids containing 28 carbons, known microtubule stabilizing cytotoxic agents isolated from the genus Tacca that have selective anti- cancer properties. Taccalonolide Q has a C2–C3 epoxide group and an enol-γ-lactone fused with the unique E ring. In addition to total antineoplastic activity with a high confidence level of 93%, taccalonolide Q demonstrates selective activity against renal cancer, sarcoma, pancreatic cancer, lymphocytic leukemia, myeloid leukemia, and genitourinary cancer.
Figure 25. The 3D graph shows the predicted and calculated pharmacological activities of taccalonolide Q (271). Taccalonolide Q, similar to other taccalonolides, is a class of highly acetoxylated pentacyclic steroids containing 28 carbons, known microtubule stabilizing cytotoxic agents isolated from the genus Tacca that have selective anti- cancer properties. Taccalonolide Q has a C2–C3 epoxide group and an enol-γ-lactone fused with the unique E ring. In addition to total antineoplastic activity with a high confidence level of 93%, taccalonolide Q demonstrates selective activity against renal cancer, sarcoma, pancreatic cancer, lymphocytic leukemia, myeloid leukemia, and genitourinary cancer.
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Table
Table 1. Biological activities of cyclopropane-containing carbon-bridged steroids.
Table 1. Biological activities of cyclopropane-containing carbon-bridged steroids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
1Antineoplastic (0.915)
Apoptosis agonist (0.892)
Antineoplastic (liver cancer) (0.822)
Chemopreventive (0.776)
Cytoprotectant (0.611)
Prostate cancer treatment (0.557)
Antimetastatic (0.528)		Anti-hypercholesterolemic (0.900)
Hypolipemic (0.897)
Atherosclerosis treatment (0.690)		Anti-osteoporotic (0.861)
Anti-eczematic (0.850)
Immunosuppressant (0.744)
Antiparkinsonian, rigidity relieving (0.720)
Anti-inflammatory (0.706)
2Chemopreventive (0.968)
Apoptosis agonist (0.879)
Antineoplastic (0.867)
Cytoprotectant (0.645)
Antimetastatic (0.578)		Hypolipemic (0.874)
Anti-hypercholesterolemic (0.649)
Cholesterol synthesis inhibitor (0.614)
Lipid metabolism regulator (0.598)
Atherosclerosis treatment (0.594)		Anti-eczematic (0.889)
Anti-inflammatory (0.860)
Antifungal (0.821)
Immunosuppressant (0.742)
Anti-psoriatic (0.720)
3Chemopreventive (0.923)
Antineoplastic (0.863)
Cytoprotectant (0.704)
Antimetastatic (0.655)
Antineoplastic (liver cancer) (0.608)
Anticarcinogenic (0.553)
Proliferative diseases treatment (0.551)
Antineoplastic (pancreatic cancer) (0.544)		Hypolipemic (0.879)
Anti-hypercholesterolemic (0.847)
Cholesterol synthesis inhibitor (0.705)
Atherosclerosis treatment (0.674)		Anti-eczematic (0.900)
Anti-inflammatory (0.843)
Antifungal (0.806)
Antipruritic (0.776)
Immunosuppressant (0.750)
Anti-psoriatic (0.744)
Anti-osteoporotic (0.716)
4Chemopreventive (0.857)
Antineoplastic (0.839)
Apoptosis agonist (0.799)
Cytoprotectant (0.646)
Antimetastatic (0.623)
Antineoplastic (pancreatic cancer) (0.514)		Hypolipemic (0.883)
Anti-hypercholesterolemic (0.739)
Cholesterol synthesis inhibitor (0.731)
Atherosclerosis treatment (0.665)		Anti-eczematic (0.871)
Anti-fungal (0.823)
Anti-inflammatory (0.805)
Anti-osteoporotic (0.707)
Anti-psoriatic (0.683)
5Chemopreventive (0.842)
Antineoplastic (0.840)
Cytoprotectant (0.680)
Antimetastatic (0.647)
Proliferative diseases treatment (0.555)
Prostatic (benign) hyperplasia treatment (0.540)
Antineoplastic (pancreatic cancer) (0.528)		Hypolipemic (0.857)
Anti-hypercholesterolemic (0.788)
Cholesterol synthesis inhibitor (0.697)
Atherosclerosis treatment (0.663)		Anti-eczematic (0.880)
Anti-inflammatory (0.808)
Anti-fungal (0.781)
Anti-psoriatic (0.719)
6Chemopreventive (0.866)
Antineoplastic (0.715)		Hypolipemic (0.703)
Cholesterol synthesis inhibitor (0.521)		Antifungal (0.878)
Anti-inflammatory (0.771)
7Chemopreventive (0.849)
Antineoplastic (0.766)		Hypolipemic (0.676)
Cholesterol synthesis inhibitor (0.554)		Antifungal (0.836)
Anti-inflammatory (0.737)
8Chemopreventive (0.713)
Antineoplastic (0.690)
Apoptosis agonist (0.584)		Hypolipemic (0.742)
Atherosclerosis treatment (0.644)
Cholesterol synthesis inhibitor (0.593)		Antifungal (0.850)
Anti-inflammatory (0.759)
9Chemopreventive (0.949)
Apoptosis agonist (0.822)
Antineoplastic (0.801)
Antimetastatic (0.558)		Hypolipemic (0.788)
Cholesterol synthesis inhibitor (0.572)
Atherosclerosis treatment (0.508)		Antifungal (0.884)
Anti-inflammatory (0.814)
10Chemopreventive (0.765)
Antineoplastic (0.701)		Hypolipemic (0.711)
Cholesterol synthesis inhibitor (0.571)
11Chemopreventive (0.836)
Apoptosis agonist (0.763)
Antineoplastic (0.755)		Hypolipemic (0.744)
Cholesterol synthesis inhibitor (0.546)
Atherosclerosis treatment (0.511)		Anti-eczematic (0.701)
12Chemopreventive (0.938)
Antineoplastic (0.804)
Apoptosis agonist (0.623)		Hypolipemic (0.736)
Atherosclerosis treatment (0.641)
Cholesterol synthesis inhibitor (0.575)		Hepatoprotectant (0.900)
13Chemopreventive (0.928)
Antineoplastic (0.812)
Apoptosis agonist (0.763)		Hypolipemic (0.800)
Atherosclerosis treatment (0.609)
Cholesterol synthesis inhibitor (0.532)		Hepatoprotectant (0.861)
14Chemopreventive (0.956)
Apoptosis agonist (0.832)
Antineoplastic (0.825)		Hypolipemic (0.847)
Atherosclerosis treatment (0.657)
Cholesterol synthesis inhibitor (0.568)		Hepatic disorders treatment (0.898)
15Chemopreventive (0.935)
Apoptosis agonist (0.821)
Antineoplastic (0.789)		Hypolipemic (0.796)
Atherosclerosis treatment (0.623)
Cholesterol synthesis inhibitor (0.618)		Hepatoprotectant (0.823)
16Chemopreventive (0.944)
Apoptosis agonist (0.808)
Antineoplastic (0.795)
Anticarcinogenic (0.628)		Hypolipemic (0.842)
Cholesterol synthesis inhibitor (0.714)
Atherosclerosis treatment (0.708)		Hepatoprotectant (0.872)
Antifungal (0.831)
Anti-inflammatory (0.823)
17Apoptosis agonist (0.864)
Antineoplastic (0.841)
Chemopreventive (0.824)
Antimetastatic (0.610)
Antineoplastic (melanoma) (0.570)
Proliferative diseases treatment (0.537)
Bone diseases treatment (0.529)
Antineoplastic (pancreatic cancer) (0.516)		Hypolipemic (0.816)
Atherosclerosis treatment (0.665)
Cholesterol synthesis inhibitor (0.579)		Anti-eczematic (0.865)
Antifungal (0.819)
18Chemopreventive (0.909)
Apoptosis agonist (0.873)
Antineoplastic (0.847)
Antimetastatic (0.629)		Hypolipemic (0.894)
Atherosclerosis treatment (0.670)
Cholesterol synthesis inhibitor (0.625)
Anti-hypercholesterolemic (0.622)		Hepatic disorders treatment (0.842)
Antiinflammatory (0.839)
Antieczematic (0.831)
Antifungal (0.809)
* Only activities with Pa > 0.5 are shown.
Table
Table 2. Biological activities of carbon-bridged steroids.
Table 2. Biological activities of carbon-bridged steroids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
19Chemopreventive (0.858)
Antineoplastic (0.815)
Apoptosis agonist (0.811)
Antimetastatic (0.620)		Hypolipemic (0.863)
Cholesterol synthesis inhibitor (0.536)		Anti-eczematic (0.809)
Anti-ulcerative (0.765)
20Chemopreventive (0.923)
Apoptosis agonist (0.847)
Antineoplastic (0.837)
Cytoprotectant (0.652)
Antimetastatic (0.634)		Hypolipemic (0.861)
Atherosclerosis treatment (0.624)
Cholesterol synthesis inhibitor (0.613)		Antieczematic (0.837)
Antiinflammatory (0.833)
Antifungal (0.829)
21Antineoplastic (0.894)
Chemopreventive (0.851)
Apoptosis agonist (0.810)
Antimetastatic (0.589)
Cytoprotectant (0.576)		Hypolipemic (0.867)
Atherosclerosis treatment (0.512)		Anti-eczematic (0.850)
Anti-inflammatory (0.755)
22Chemopreventive (0.959)
Antineoplastic (0.886)
Apoptosis agonist (0.858)
Cytoprotectant (0.701)
Antineoplastic (liver cancer) (0.641)
Antimetastatic (0.607)
Proliferative diseases treatment (0.554)
Prostate cancer treatment (0.510)		Hypolipemic (0.877)
Atherosclerosis treatment (0.676)
Anti-hypercholesterolemic (0.609)
Cholesterol synthesis inhibitor (0.568)
Lipid metabolism regulator (0.553)		Hepatic disorders treatment (0.921)
Anti-eczematic (0.877)
Anti-inflammatory (0.872)
Anti-psoriatic (0.808)
23Chemopreventive (0.967)
Antineoplastic (0.884)
Apoptosis agonist (0.881)
Cytoprotectant (0.638)
Antimetastatic (0.615)		Hypolipemic (0.881)
Atherosclerosis treatment (0.654)
Cholesterol synthesis inhibitor (0.568)
Lipid metabolism regulator (0.544)		Anti-eczematic (0.888)
Anti-inflammatory (0.827)
Antifungal (0.800)
Anti-psoriatic (0.739)
24Chemopreventive (0.952)
Apoptosis agonist (0.897)
Antineoplastic (0.857)
Cytoprotectant (0.677)
Antimetastatic (0.657)
Anticarcinogenic (0.561)
Antineoplastic (liver cancer) (0.552)
Proliferative diseases treatment (0.538)
Antineoplastic (pancreatic cancer) (0.537)		Hypolipemic (0.900)
Atherosclerosis treatment (0.689)
Cholesterol synthesis inhibitor (0.671)
Anti-hypercholesterolemic (0.662)
Lipid metabolism regulator (0.529)		Anti-eczematic (0.879)
Anti-psoriatic (0.709)
25Chemopreventive (0.991)
Antineoplastic (0.915)
Apoptosis agonist (0.879)
Anticarcinogenic (0.787)
Proliferative diseases treatment (0.735)
Antimetastatic (0.579)
Antineoplastic (sarcoma) (0.533)		Hypolipemic (0.825)
Anti-hypercholesterolemic (0.816)
Atherosclerosis treatment (0.669)		Hepatoprotectant (0.987)
Antifungal (0.893)
Anti-inflammatory (0.882)
26Chemopreventive (0.881)
Antineoplastic (0.854)
Apoptosis agonist (0.825)
Antimetastatic (0.544)		Hypolipemic (0.833)
Cholesterol synthesis inhibitor (0.821)
Anti-hypercholesterolemic (0.791)
Lipoprotein disorders treatment (0.717)		Antifungal (0.867)
Anti-eczematic (0.830)
Anti-inflammatory (0.804)
27Antineoplastic (0.867)
Apoptosis agonist (0.742)
Chemopreventive (0.707)
Cytoprotectant (0.656)
Proliferative diseases treatment (0.606)
Antimetastatic (0.565)
Chemoprotective (0.558)
Antineoplastic (pancreatic cancer) (0.544)
Anticarcinogenic (0.541)		Hypolipemic (0.698)
Atherosclerosis treatment (0.594)
Anti-hypercholesterolemic (0.550)
Cholesterol synthesis inhibitor (0.521)		Antieczematic (0.886)
Hepatoprotectant (0.861)
Antipsoriatic (0.714)
28Antineoplastic (0.875)
Chemopreventive (0.780)
Apoptosis agonist (0.768)
Proliferative diseases treatment (0.687)
Cytoprotectant (0.685)
Anticarcinogenic (0.639)
Antimetastatic (0.590)
Antineoplastic (pancreatic cancer) (0.549)		Anti-hypercholesterolemic (0.714)
Hypolipemic (0.698)
Antipruritic (0.639)
Atherosclerosis treatment (0.582)
Cholesterol synthesis inhibitor (0.576)		Hepatoprotectant (0.858)
Immunosuppressant (0.751)
Hepatic disorders treatment (0.686)
29Antineoplastic (0.881)
Chemopreventive (0.791)
Apoptosis agonist (0.669)
Proliferative diseases treatment (0.666)
Anticarcinogenic (0.657)
Cytoprotectant (0.627)
Chemoprotective (0.565)
Antimetastatic (0.559)
Antineoplastic (pancreatic cancer) (0.547)		Anti-hypercholesterolemic (0.738)
Hypolipemic (0.707)
Cholesterol synthesis inhibitor (0.559)
Atherosclerosis treatment (0.539)		Anti-eczematic (0.898)
Hepatoprotectant (0.866)
30Antineoplastic (0.814)
Apoptosis agonist (0.801)
Chemopreventive (0.782)
Cytoprotectant (0.604)
Antineoplastic (pancreatic cancer) (0.565)
Antimetastatic (0.526)		Hypolipemic (0.830)
Cholesterol synthesis inhibitor (0.679)
Anti-hypercholesterolemic (0.618)
Atherosclerosis treatment (0.546)		Anti-eczematic (0.847)
Antiinflammatory (0.794)
Antifungal (0.789)
Immunosuppressant (0.733)
Antiosteoporotic (0.727)
31Antineoplastic (0.797)
Apoptosis agonist (0.766)
Chemopreventive (0.762)
Cytoprotectant (0.585)
Antineoplastic (pancreatic cancer) (0.559)
Prostatic (benign) hyperplasia treatment (0.519)
Antimetastatic (0.516)		Hypolipemic (0.742)
Cholesterol synthesis inhibitor (0.583)		Anti-eczematic (0.831)
Antiinflammatory (0.771)
Antifungal (0.751)
32Antineoplastic (0.803)
Apoptosis agonist (0.719)
Chemopreventive (0.696)
Prostatic (benign) hyperplasia treatment (0.599)
Antineoplastic (pancreatic cancer) (0.538)		 Erythropoiesis stimulant (0.743)
Diuretic (0.629)
Anesthetic general (0.611)
33Chemopreventive (0.889)
Antineoplastic (0.837)
Apoptosis agonist (0.751)
Cytoprotectant (0.720)
Antineoplastic (pancreatic cancer) (0.563)
Antineoplastic enhancer (0.558)
Antimetastatic (0.543)		Hypolipemic (0.752)
Anti-hypercholesterolemic (0.669)
Cholesterol synthesis inhibitor (0.607)
Atherosclerosis treatment (0.527)
34Apoptosis agonist (0.854)
Antineoplastic (0.846)
Chemopreventive (0.831)
Cytoprotectant (0.687)
Antimetastatic (0.635)
Proliferative diseases treatment (0.577)
Antineoplastic (pancreatic cancer) (0.559)		Hypolipemic (0.875)
Anti-hypercholesterolemic (0.681)
Atherosclerosis treatment (0.639)
Cholesterol synthesis inhibitor (0.599)		Anti-eczematic (0.900)
35Antineoplastic (0.816)
Apoptosis agonist (0.799)
Chemopreventive (0.738)
Cytoprotectant (0.661)
Antimetastatic (0.624)
Proliferative diseases treatment (0.580)
Antineoplastic (pancreatic cancer) (0.547)		Hypolipemic (0.852)
Atherosclerosis treatment (0.623)
Anti-hypercholesterolemic (0.594)
Cholesterol synthesis inhibitor (0.592)		Anti-eczematic (0.880)
36Antineoplastic (0.886)
Chemopreventive (0.819)
Apoptosis agonist (0.769)
Antimetastatic (0.630)
Antineoplastic (renal cancer) (0.593)
Antineoplastic (lymphocytic leukemia) (0.525)
Prostate cancer treatment (0.511)		Hypolipemic (0.795)Diabetic neuropathy treatment (0.884)
Antidiabetic symptomatic (0.778)
* Only activities with Pa > 0.5 are shown.
Table
Table 3. Biological activities of carbon-bridged steroids.
Table 3. Biological activities of carbon-bridged steroids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
37Antineoplastic (0.877)
Apoptosis agonist (0.771)
Antiparasitic (0.631)
Chemopreventive (0.629)
Antimetastatic (0.577)		 Spasmolytic, urinary (0.696)
38Antineoplastic (0.852)
Apoptosis agonist (0.785)
Chemopreventive (0.665)
Antimetastatic (0.578)		 Spasmolytic, urinary (0.671)
39Antineoplastic (0.898)
Chemopreventive (0.849)
Apoptosis agonist (0.823)
Antimetastatic (0.554)		Hypolipemic (0.581)
40Antineoplastic (0.785)
Chemopreventive (0.715)
Apoptosis agonist (0.588)		Hypolipemic (0.556)
41Chemopreventive (0.994)
Antineoplastic (0.910)
Apoptosis agonist (0.826)		Hypolipemic (0.651)
42Antineoplastic (0.775)
Apoptosis agonist (0.716)
Chemopreventive (0.626)
Antimetastatic (0.583)		 Alzheimer’s disease treatment (0.831)
Neurodegenerative diseases treatment (0.818)
Antiparkinsonian (0.556)
43Antineoplastic (0.842)
Apoptosis agonist (0.575)
Antimetastatic (0.505)
44Antineoplastic (0.860)
Apoptosis agonist (0.851)
Chemopreventive (0.797)
Antimetastatic (0.585)
Antineoplastic enhancer (0.571)
Antineoplastic (sarcoma) (0.548)		Hypolipemic (0.809)
45Antineoplastic (0.857)
Chemopreventive (0.731)
Apoptosis agonist (0.702)
Antimetastatic (0.589)		Hypolipemic (0.787)
46Antineoplastic (0.921)
Apoptosis agonist (0.822)
Chemopreventive (0.748)
Antimetastatic (0.607)
Antineoplastic (renal cancer) (0.538)		Hypolipemic (0.590)
Cholesterol synthesis inhibitor (0.525)
47Chemopreventive (0.910)
Antineoplastic (0.892)
Apoptosis agonist (0.887)
Anticarcinogenic (0.554)
Antineoplastic (sarcoma) (0.554)
Antineoplastic (pancreatic cancer) (0.543)		Hypolipemic (0.626)Antithrombotic (0.689)
Alzheimer’s disease treatment (0.540)
48Antineoplastic (0.844)
Apoptosis agonist (0.814)
Chemopreventive (0.790)
Antimetastatic (0.602)
Antineoplastic (lymphocytic leukemia) (0.524)		Hypolipemic (0.825)
Cholesterol synthesis inhibitor (0.622)
Atherosclerosis treatment (0.576)		Antiviral (HIV) (0.520)
49Chemopreventive (0.967)
Antineoplastic (0.906)
Apoptosis agonist (0.655)		Hypolipemic (0.646)
50Chemopreventive (0.936)
Antineoplastic (0.895)
Apoptosis agonist (0.722)
Anticarcinogenic (0.604)
Antineoplastic (genitourinary cancer) (0.555)
Antimetastatic (0.555)		Hypolipemic (0.782)Diabetic neuropathy treatment (0.696)
Antidiabetic (0.610)
51Antineoplastic (0.848)
Apoptosis agonist (0.767)
Chemopreventive (0.607)
Antimetastatic (0.587)		Hypolipemic (0.847)Antiprotozoal (Plasmodium) (0.629)
52Antineoplastic (0.820)
Chemopreventive (0.735)
Cytoprotectant (0.629)
Apoptosis agonist (0.598)		Anti-hypercholesterolemic (0.614)
Atherosclerosis treatment (0.589)
Cholesterol synthesis inhibitor (0.581)
* Only activities with Pa > 0.5 are shown.
Table
Table 4. Biological activities of carbon-bridged steroids.
Table 4. Biological activities of carbon-bridged steroids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
53Apoptosis agonist (0.768)
Antineoplastic (0.759)
Chemopreventive (0.574)
Antimetastatic (0.514)
Antineoplastic (pancreatic cancer) (0.509)		 Antiprotozoal (Plasmodium) (0.755)
54Apoptosis agonist (0.778)
Antineoplastic (0.770)
Chemopreventive (0.634)
Antineoplastic (pancreatic cancer) (0.562)
Antineoplastic (sarcoma) (0.555)
Antimetastatic (0.547)		Hypolipemic (0.506)Antiprotozoal (Plasmodium) (0.724)
55Antineoplastic (0.881)
Apoptosis agonist (0.692)
Antimetastatic (0.602)		Hypolipemic (0.775)Cardiotonic (0.691)
56Antineoplastic (0.752)
Apoptosis agonist (0.698)
Chemopreventive (0.619)
57Antineoplastic (0.752)
Apoptosis agonist (0.698)
58Antineoplastic (0.825)
Apoptosis agonist (0.690)
59Antineoplastic (0.881)
Apoptosis agonist (0.728)
Chemopreventive (0.709)
Antineoplastic (genitourinary cancer) (0.594)
Antimetastatic (0.546)
Antineoplastic (sarcoma) (0.532)
Antineoplastic (pancreatic cancer) (0.503)		Hypolipemic (0.805)
60Antineoplastic (0.804)
Chemopreventive (0.700)
Apoptosis agonist (0.669)
Antineoplastic (sarcoma) (0.521)
Antineoplastic (renal cancer) (0.512)		Hypolipemic (0.693)
Lipid metabolism regulator (0.525)		Alzheimer’s disease treatment (0.571)
61Antineoplastic (0.888)
Chemopreventive (0.864)
Anticarcinogenic (0.569)
Antimetastatic (0.559)		Hypolipemic (0.827)
62Antineoplastic (0.869)
Chemopreventive (0.862)
Antimetastatic (0.560)
Antineoplastic (sarcoma) (0.503)		Hypolipemic (0.815)
Lipid metabolism regulator (0.520)		Antithrombotic (0.608)
63Antineoplastic (0.811)
Chemopreventive (0.790)
Apoptosis agonist (0.774)
Antineoplastic (pancreatic cancer) (0.551)
Antimetastatic (0.518)		Hypolipemic (0.503)Genital warts treatment (0.759)
64Antineoplastic (0.837)
Apoptosis agonist (0.803)
Chemopreventive (0.748)
Antineoplastic (myeloid leukemia) (0.704)		Hypolipemic (0.708)
Lipid metabolism regulator (0.501)		Immunosuppressant (0.632)
65Chemopreventive (0.895)
Antineoplastic (0.875)
Antineoplastic (myeloid leukemia) (0.677)		Hypolipemic (0.733)
* Only activities with Pa > 0.5 are shown.
Table
Table 5. Biological activities of carbon-bridged steroids.
Table 5. Biological activities of carbon-bridged steroids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
66Chemopreventive (0.950)
Antineoplastic (0.846)
Proliferative diseases treatment (0.745)
Anticarcinogenic (0.743)
Apoptosis agonist (0.701)
Antimetastatic (0.570)
Antineoplastic (myeloid leukemia) (0.557)
Antineoplastic (pancreatic cancer) (0.505)		Anti-hypercholesterolemic (0.769)
Hypolipemic (0.752)
Lipid metabolism regulator (0.730)
Atherosclerosis treatment (0.532)		Hepatoprotectant (0.912)
67Chemopreventive (0.948)
Antineoplastic (0.861)
Anticarcinogenic (0.757)
Apoptosis agonist (0.740)
Proliferative diseases treatment (0.712)
Antimetastatic (0.576)
Antineoplastic (myeloid leukemia) (0.550)
Antineoplastic (lymphocytic leukemia) (0.520)		Hypolipemic (0.744)
Anti-hypercholesterolemic (0.650)
Lipid metabolism regulator (0.649)		Hepatoprotectant (0.903)
68Chemopreventive (0.954)
Antineoplastic (0.869)
Apoptosis agonist (0.803)
Anticarcinogenic (0.706)		Hypolipemic (0.773)
Lipid metabolism regulator (0.758)
Anti-hypercholesterolemic (0.751)		Hepatoprotectant (0.866)
69Chemopreventive (0.943)
Antineoplastic (0.835)
Proliferative diseases treatment (0.719)
Apoptosis agonist (0.690)
Anticarcinogenic (0.656)
Antineoplastic (pancreatic cancer) (0.549)
Antimetastatic (0.544)
Antineoplastic (sarcoma) (0.505)		Anti-hypercholesterolemic (0.798)
Hypolipemic (0.675)
Lipid metabolism regulator (0.513)		Hepatoprotectant (0.834)
70Chemopreventive (0.958)
Antineoplastic (0.859)
Apoptosis agonist (0.713)
Anticarcinogenic (0.634)
Proliferative diseases treatment (0.597)
Antimetastatic (0.562)
Antineoplastic (sarcoma) (0.535)
Antineoplastic (myeloid leukemia) (0.531)		Hypolipemic (0.754)
Anti-hypercholesterolemic (0.606)
Lipid metabolism regulator (0.511)		Anti-eczematic (0.955)
Anti-psoriatic (0.592)
71Chemopreventive (0.974)
Antineoplastic (0.844)
Anticarcinogenic (0.782)
Proliferative diseases treatment (0.718)
Antimetastatic (0.567)
Antineoplastic (myeloid leukemia) (0.560)
Antineoplastic (lymphocytic leukemia) (0.540)		Hypolipemic (0.730)
Lipid metabolism regulator (0.599)
Anti-hypercholesterolemic (0.519)		Respiratory analeptic (0.894)
72Chemopreventive (0.808)
Antineoplastic (0.782)
Apoptosis agonist (0.683)		Lipid metabolism regulator (0.662)
Hypolipemic (0.652)
73Antineoplastic (0.789)
Chemopreventive (0.787)
Apoptosis agonist (0.761)
Antimetastatic (0.576)
Proliferative diseases treatment (0.568)
Antineoplastic (myeloid leukemia) (0.552)
Cytoprotectant (0.509)
Anticarcinogenic (0.503)		Lipid metabolism regulator (0.843)
Hypolipemic (0.798)
Cholesterol synthesis inhibitor (0.635)
Anti-hypercholesterolemic (0.628)		Antithrombotic (0.638)
74Antineoplastic (0.790)
Apoptosis agonist (0.736)
Antineoplastic (liver cancer) (0.640)		Hypolipemic (0.597)Genital warts treatment (0.831)
75Antineoplastic (0.764)
Chemopreventive (0.677)
Antineoplastic (liver cancer) (0.571)
Apoptosis agonist (0.531)		Hypolipemic (0.679)Genital warts treatment (0.630)
76Antineoplastic (0.688)Hypolipemic (0.553)Genital warts treatment (0.635)
77Antineoplastic (0.867)
Apoptosis agonist (0.820)
Antineoplastic (liver cancer) (0.561)		Hypolipemic (0.590)Genital warts treatment (0.635)
* Only activities with Pa > 0.5 are shown.
Table
Table 6. Biological activities of carbon-bridged steroids.
Table 6. Biological activities of carbon-bridged steroids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
78Antineoplastic (0.820) Genital warts treatment (0.780)
79Antineoplastic (0.841) Antimitotic (0.642)
80Antineoplastic (0.820) Genital warts treatment (0.780)
81Antineoplastic (0.841) Prostate disorders treatment (0.650)
82Antineoplastic (0.831) Genital warts treatment (0.854)
83Antineoplastic (0.866) Genital warts treatment (0.707)
84Antineoplastic (0.759)
Chemopreventive (0.711)
Apoptosis agonist (0.644)
Cytoprotectant (0.631)
Antimetastatic (0.587)		Hypolipemic (0.764)
Atherosclerosis treatment (0.600)
Cholesterol synthesis inhibitor (0.525)
Lipid metabolism regulator (0.521)
Anti-hypercholesterolemic (0.519)
85Antineoplastic (0.801)
Chemopreventive (0.780)
Apoptosis agonist (0.673)
Cytoprotectant (0.621)
Antimetastatic (0.597)		Hypolipemic (0.765)
Cholesterol synthesis inhibitor (0.577)
Lipid metabolism regulator (0.500)		Immunosuppressant (0.727)
86Antineoplastic (0.773)
Apoptosis agonist (0.687)
Chemopreventive (0.609)
Cytoprotectant (0.583)		Cholesterol synthesis inhibitor (0.556)
Hypolipemic (0.511)		Anti-ischemic, cerebral (0.973)
87Antineoplastic (0.825)
Antineoplastic (myeloid leukemia) (0.645)
Apoptosis agonist (0.573)
Antineoplastic (carcinoma) (0.504)		 Alzheimer’s disease treatment (0.824)
Neurodegenerative diseases treatment (0.809)
Psychotropic (0.700)
88Antineoplastic (0.889)
Apoptosis agonist (0.580)
Antimetastatic (0.515)		Hypolipemic (0.508)Hepatic disorders treatment (0.931)
89Antineoplastic (0.870)
Apoptosis agonist (0.759)		 Hepatic disorders treatment (0.952)
Hepatoprotectant (0.514)
* Only activities with Pa > 0.5 are shown.
Table
Table 7. Biological activities of carbon-bridged steroids.
Table 7. Biological activities of carbon-bridged steroids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
90Antineoplastic (0.715) Immunosuppressant (0.770)
Cardiotonic (0.726)
91Antineoplastic (0.744) Immunosuppressant (0.735)
Cardiotonic (0.688)
92Antineoplastic (0.901)
Apoptosis agonist (0.818)
Chemopreventive (0.732)
Cytostatic (0.606)
Antimetastatic (0.581)
Anticarcinogenic (0.546)
Antineoplastic (breast cancer) (0.539)		Anti-hypercholesterolemic (0.625)
Hypolipemic (0.617)		Respiratory analeptic (0.902)
Antidepressant (0.776)
93Antineoplastic (0.839)
Proliferative diseases treatment (0.804)
Chemopreventive (0.792)
Anticarcinogenic (0.722)
Apoptosis agonist (0.701)
Antineoplastic (sarcoma) (0.567)
Antimetastatic (0.503)		Lipoprotein disorders treatment (0.800)
Anti-hypercholesterolemic (0.677)		Antidiabetic (0.902)
Spasmolytic (0.705)
Cardiotonic (0.682)
94Antineoplastic (0.877)
Chemopreventive (0.709)
Apoptosis agonist (0.707)
Antineoplastic (sarcoma) (0.673)
Proliferative diseases treatment (0.630)
Antineoplastic (lymphocytic leukemia) (0.560)
Prostate disorders treatment (0.557)
Cytostatic (0.557)
Anticarcinogenic (0.556)
Antineoplastic (pancreatic cancer) (0.538)
Antineoplastic (breast cancer) (0.522)
Antimetastatic (0.505)		Anti-hypercholesterolemic (0.862)
Lipid metabolism regulator (0.549)
Hypolipemic (0.532)		Respiratory analeptic (0.950)
95Antineoplastic (0.856)
Chemopreventive (0.701)
Antineoplastic (sarcoma) (0.688)
Proliferative diseases treatment (0.640)
Apoptosis agonist (0.615)
Anticarcinogenic (0.588)
Cytostatic (0.584)
Antineoplastic (lymphocytic leukemia) (0.569)
Antineoplastic (pancreatic cancer) (0.534)
Antineoplastic (renal cancer) (0.531)
Antimetastatic (0.512)		Anti-hypercholesterolemic (0.806)
Lipid metabolism regulator (0.539)		Respiratory analeptic (0.953)
Hepatoprotectant (0.901)
96Antineoplastic (0.937)
Apoptosis agonist (0.827)
Chemopreventive (0.757)
Anticarcinogenic (0.741)
Proliferative diseases treatment (0.718)
Antineoplastic (sarcoma) (0.673)
Antineoplastic (lymphocytic leukemia) (0.587)
Antimetastatic (0.540)
Antineoplastic (breast cancer) (0.525)
Antineoplastic (pancreatic cancer) (0.524)
Antineoplastic (renal cancer) (0.521)		Anti-hypercholesterolemic (0.863)
Lipid metabolism regulator (0.555)		Respiratory analeptic (0.952)
97Antineoplastic (0.801)
Antineoplastic (breast cancer) (0.603)
Apoptosis agonist (0.589)		 Antidepressant (0.946)
Mood disorders treatment (0.944)
Psychotropic (0.922)
98Antineoplastic (0.763)
Antineoplastic (genitourinary cancer) (0.537)
Antimetastatic (0.514)		 Antiprotozoal (0.955)
Antiprotozoal (Plasmodium) (0.950)
99Antineoplastic (0.875)
Chemopreventive (0.648)
Antineoplastic (sarcoma) (0.633)
Apoptosis agonist (0.630)
Proliferative diseases treatment (0.566)
Antimetastatic (0.523)
Antineoplastic (lymphocytic leukemia) (0.512)
Anticarcinogenic (0.506)		 Anti-ischemic, cerebral (0.770)
Immunosuppressant (0.747)
100Antineoplastic (0.875)
Chemopreventive (0.648)
Antineoplastic (sarcoma) (0.633)
Apoptosis agonist (0.630)
Proliferative diseases treatment (0.566)
Antimetastatic (0.523)
Anticarcinogenic (0.506)		 Anti-ischemic, cerebral (0.770)
Immunosuppressant (0.747)
101Antineoplastic (0.869)
Anticarcinogenic (0.823)
Proliferative diseases treatment (0.781)
Chemopreventive (0.717)
Apoptosis agonist (0.667)
Antineoplastic (sarcoma) (0.560)
Antimetastatic (0.516)		 Anti-ischemic, cerebral (0.702)
102Cytoprotectant (0.758)
Antineoplastic (0.720)
Chemopreventive (0.591)
Apoptosis agonist (0.564)		Hypolipemic (0.679)
Anti-hypercholesterolemic (0.599)
Atherosclerosis treatment (0.541)
Cholesterol synthesis inhibitor (0.533)		Choleretic (0.733)
* Only activities with Pa > 0.5 are shown.
Table
Table 8. Biological activities of sterols and triterpenoids with cyclopropane ring in the side chain.
Table 8. Biological activities of sterols and triterpenoids with cyclopropane ring in the side chain.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
103Antineoplastic (0.911)
Apoptosis agonist (0.677)
Chemopreventive (0.658)
Cytoprotectant (0.630)
Antineoplastic (sarcoma) (0.558)		Anti-hypercholesterolemic (0.791)
Hypolipemic (0.789)		Choleretic (0.885)
104Antineoplastic (0.822)
Proliferative diseases treatment (0.668)
Cytoprotectant (0.635)
Chemopreventive (0.557)
Apoptosis agonist (0.536)
Antineoplastic (sarcoma) (0.530)
Antimetastatic (0.518)		Anti-hypercholesterolemic (0.862)
Hypolipemic (0.757)
Cholesterol synthesis inhibitor (0.517)		Anti-ischemic, cerebral (0.952)
Choleretic (0.935)
105Antineoplastic (0.934)
Proliferative diseases treatment (0.644)
Prostate cancer treatment (0.585)
Antineoplastic (sarcoma) (0.575)
Cytoprotectant (0.544)
Antineoplastic (renal cancer) (0.520)
Apoptosis agonist (0.517)		Anti-hypercholesterolemic (0.828)
Hypolipemic (0.709)		Choleretic (0.879)
Anti-ischemic, cerebral (0.674)
106Antineoplastic (0.839)
Chemopreventive (0.697)
Cytoprotectant (0.670)
Proliferative diseases treatment (0.642)
Apoptosis agonist (0.607)
Prostatic (benign) hyperplasia treatment (0.520)
Antimetastatic (0.515)
Antineoplastic (renal cancer) (0.513)		Anti-hypercholesterolemic (0.850)
Hypolipemic (0.728)		Choleretic (0.910)
107Antineoplastic (0.849)
Chemopreventive (0.789)
Proliferative diseases treatment (0.785)
Apoptosis agonist (0.750)
Cytoprotectant (0.717)
Anticarcinogenic (0.658)
Prostate cancer treatment (0.601)
Antimetastatic (0.584)
Antineoplastic (sarcoma) (0.578)
Antineoplastic (pancreatic cancer) (0.547)		Anti-hypercholesterolemic (0.964)
Hypolipemic (0.849)
Anti-hyperlipoproteinemic (0.801)
Cholesterol synthesis inhibitor (0.671)
Atherosclerosis treatment (0.610)		Respiratory analeptic (0.964)
Choleretic (0.856)
108Antineoplastic (0.861)
Antimetastatic (0.552)		 Angiogenesis inhibitor (0.928)
109Antineoplastic (0.821)
Chemopreventive (0.743)
Prostatic (benign) hyperplasia treatment (0.663)
Cytoprotectant (0.660)
Proliferative diseases treatment (0.648)
Apoptosis agonist (0.594)
Antimetastatic (0.550)
Prostate cancer treatment (0.538)		Anti-hypercholesterolemic (0.923)
Hypolipemic (0.732)
Atherosclerosis treatment (0.643)
Cholesterol synthesis inhibitor (0.640)		Respiratory analeptic (0.844)
Anesthetic general (0.834)
110Antineoplastic (0.821)
Chemopreventive (0.743)
Prostatic (benign) hyperplasia treatment (0.663)
Cytoprotectant (0.660)
Proliferative diseases treatment (0.648)
Apoptosis agonist (0.594)
Antimetastatic (0.550)
Prostate cancer treatment (0.538)		Anti-hypercholesterolemic (0.923)
Hypolipemic (0.732)
Atherosclerosis treatment (0.643)
Cholesterol synthesis inhibitor (0.640)
111Antineoplastic (0.898)
Apoptosis agonist (0.586)
Cytoprotectant (0.553)
Antineoplastic (sarcoma) (0.516)		Hypolipemic (0.778)
Anti-hypercholesterolemic (0.520)		Choleretic (0.711)
Antiprotozoal (Plasmodium) (0.640)
112Antineoplastic (0.922)
Prostate disorders treatment (0.553)
Proliferative diseases treatment (0.545)
Antineoplastic (sarcoma) (0.536)		Hypolipemic (0.692)
Anti-hypercholesterolemic (0.578)		Choleretic (0.707)
113Antineoplastic (0.845)
Chemopreventive (0.734)
Cytoprotectant (0.730)
Proliferative diseases treatment (0.700)
Antimetastatic (0.634)
Anticarcinogenic (0.607)
Prostate cancer treatment (0.533)		Anti-hypercholesterolemic (0.909)
Hypolipemic (0.872)
Atherosclerosis treatment (0.639)
Cholesterol synthesis inhibitor (0.584)		Choleretic (0.962)
114Antineoplastic (0.832)
Cytoprotectant (0.668)
Proliferative diseases treatment (0.659)
Chemopreventive (0.611)
Antineoplastic (sarcoma) (0.555)
Prostatic (benign) hyperplasia treatment (0.500)		Anti-hypercholesterolemic (0.865)
Hypolipemic (0.743)
Atherosclerosis treatment (0.553)
Cholesterol synthesis inhibitor (0.514)		Choleretic (0.934)
Respiratory analeptic (0.897)
115Antineoplastic (0.858)
Cytoprotectant (0.699)
Antineoplastic (sarcoma) (0.685)
Antimetastatic (0.591)
Antineoplastic (renal cancer) (0.585)
Prostate disorders treatment (0.578)
Proliferative diseases treatment (0.554)
Apoptosis agonist (0.549)
Antineoplastic (pancreatic cancer) (0.531)
Chemopreventive (0.522)
Antineoplastic (genitourinary cancer) (0.506)		Hypolipemic (0.713)Immunosuppressant (0.780)
116Antineoplastic (0.682)
Prostate disorders treatment (0.670)
Apoptosis agonist (0.613)
Chemopreventive (0.604)
Cytoprotectant (0.566)
Prostatic (benign) hyperplasia treatment (0.532)
Antimetastatic (0.527)		Anti-hypercholesterolemic (0.836)
Cholesterol synthesis inhibitor (0.587)
Hypolipemic (0.563)
117Antineoplastic (0.706)
Prostate disorders treatment (0.630)
Cytoprotectant (0.600)
Antimetastatic (0.555)
Prostatic (benign) hyperplasia treatment (0.510)		Hypolipemic (0.587)
Cholesterol synthesis inhibitor (0.509)		Immunosuppressant (0.720)
* Only activities with Pa > 0.5 are shown.
Table
Table 9. Biological activities of sterols and triterpenoids with cyclopropane ring in the side chain.
Table 9. Biological activities of sterols and triterpenoids with cyclopropane ring in the side chain.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
118Chemopreventive (0.963)
Proliferative diseases treatment (0.931)
Antineoplastic (0.885)
Anticarcinogenic (0.861)
Apoptosis agonist (0.790)
Antineoplastic (sarcoma) (0.624)
Antimetastatic (0.569)
Antineoplastic (liver cancer) (0.529)
Antineoplastic (lymphocytic leukemia) (0.516)
Antineoplastic (pancreatic cancer) (0.502)		Anti-hypercholesterolemic (0.953)
Hypolipemic (0.758)
Lipid metabolism regulator (0.674)
Atherosclerosis treatment (0.513)		Respiratory analeptic (0.982)
Hepatoprotectant (0.979)
119Chemopreventive (0.960)
Proliferative diseases treatment (0.921)
Antineoplastic (0.904)
Anticarcinogenic (0.851)
Apoptosis agonist (0.824)
Antineoplastic (sarcoma) (0.633)
Antimetastatic (0.569)
Prostate disorders treatment (0.548)
Antineoplastic (liver cancer) (0.543)		Anti-hypercholesterolemic (0.939)
Hypolipemic (0.746)
Lipid metabolism regulator (0.599)		Respiratory analeptic (0.987)
Hepatoprotectant (0.984)
Antiprotozoal (Leishmania) (0.880)
120Apoptosis agonist (0.975)
Chemopreventive (0.916)
Antineoplastic (0.845)
Prostate disorders treatment (0.615)
Cytoprotectant (0.611)
Antimetastatic (0.543)		Atherosclerosis treatment (0.731)
Hypolipemic (0.632)		Antiprotozoal (Plasmodium) (0.768)
121Antineoplastic (0.845)
Chemopreventive (0.832)
Apoptosis agonist (0.822)
Proliferative diseases treatment (0.818)
Prostate cancer treatment (0.584)
Antimetastatic (0.537)
Antineoplastic (sarcoma) (0.531)		Anti-hypercholesterolemic (0.969)
Hypolipemic (0.810)
Lipid metabolism regulator (0.716)
Cholesterol synthesis inhibitor (0.707)
Atherosclerosis treatment (0.586)		Wound healing agent (0.916)
Respiratory analeptic (0.902)
122Antineoplastic (0.818)
Chemopreventive (0.742)
Apoptosis agonist (0.690)
Prostatic (benign) hyperplasia treatment (0.660)
Cytoprotectant (0.642)
Proliferative diseases treatment (0.622)
Antimetastatic (0.556)
Prostate cancer treatment (0.541)		Anti-hypercholesterolemic (0.903)
Hypolipemic (0.709)
Atherosclerosis treatment (0.613)
Cholesterol synthesis inhibitor (0.595)		Anesthetic general (0.884)
Respiratory analeptic (0.876)
123Chemopreventive (0.857)
Antineoplastic (0.850)
Apoptosis agonist (0.759)
Cytoprotectant (0.723)
Prostatic (benign) hyperplasia treatment (0.685)
Proliferative diseases treatment (0.671)
Antimetastatic (0.568)
Prostate cancer treatment (0.557)
Antineoplastic (pancreatic cancer) (0.530)
Anticarcinogenic (0.517)
Antineoplastic (breast cancer) (0.516)		Anti-hypercholesterolemic (0.961)
Hypolipemic (0.755)
Atherosclerosis treatment (0.690)
Cholesterol synthesis inhibitor (0.652)
Anti-hyperlipoproteinemic (0.607)
Lipid metabolism regulator (0.572)		Respiratory analeptic (0.901)
124Antineoplastic (0.753)
Apoptosis agonist (0.677)
Prostate disorders treatment (0.584)
125Antineoplastic (0.791)
Prostate disorders treatment (0.613)
Proliferative diseases treatment (0.556)		Anti-hypercholesterolemic (0.704)
Hypolipemic (0.556)
Cholesterol synthesis inhibitor (0.530)		Anti-inflammatory (0.833)
126Antineoplastic (0.697)Anti-hypercholesterolemic (0.555)
Cholesterol synthesis inhibitor (0.504)
127Apoptosis agonist (0.756)
Antineoplastic (0.660)		 Antiprotozoal (Plasmodium) (0.687)
128Antineoplastic (0.731)
Apoptosis agonist (0.599)		Anti-hypercholesterolemic (0.571)
Hypolipemic (0.546)
129Antineoplastic (0.824)
Chemopreventive (0.726)
Proliferative diseases treatment (0.657)
Prostatic (benign) hyperplasia treatment (0.656)
Cytoprotectant (0.654)
Apoptosis agonist (0.637)
Antimetastatic (0.539)
Prostate cancer treatment (0.538)
Antineoplastic (sarcoma) (0.537)
Antineoplastic (breast cancer) (0.507)		Anti-hypercholesterolemic (0.935)
Hypolipemic (0.731)
Anti-hyperlipoproteinemic (0.689)
Cholesterol synthesis inhibitor (0.600)		Anti-eczematic (0.961)
Respiratory analeptic (0.904)
130Antineoplastic (0.813)
Chemopreventive (0.717)
Proliferative diseases treatment (0.695)
Cytoprotectant (0.670)
Prostatic (benign) hyperplasia treatment (0.649)
Antineoplastic (sarcoma) (0.628)
Apoptosis agonist (0.608)
Prostate cancer treatment (0.559)
Anticarcinogenic (0.556)
Antineoplastic (pancreatic cancer) (0.550)
Antineoplastic (breast cancer) (0.528)
Antimetastatic (0.524)
Antineoplastic (renal cancer) (0.514)		Anti-hypercholesterolemic (0.908)
Hypolipemic (0.726)
Cholesterol synthesis inhibitor (0.589)
Anti-hyperlipoproteinemic (0.587)		Anti-eczematic (0.960)
Respiratory analeptic (0.905)
* Only activities with Pa > 0.5 are shown.
Table
Table 10. Biological activities of cyclopropane-containing steroids and triterpenoids.
Table 10. Biological activities of cyclopropane-containing steroids and triterpenoids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
131Antineoplastic (0.780)
Apoptosis agonist (0.559)
Antimetastatic (0.549)
Antineoplastic (myeloid leukemia) (0.537)		Hypolipemic (0.577)
Lipid metabolism regulator (0.567)
132Antineoplastic (0.780)
Apoptosis agonist (0.559)
Antimetastatic (0.549)
Antineoplastic (myeloid leukemia) (0.537)		Hypolipemic (0.577)
Lipid metabolism regulator (0.567)
133Antineoplastic (0.769)
Apoptosis agonist (0.576)
Antimetastatic (0.547)		Hypolipemic (0.660)
Lipid metabolism regulator (0.604)
134Antineoplastic (0.769)
Apoptosis agonist (0.576)
Antimetastatic (0.547)		Hypolipemic (0.660)
Lipid metabolism regulator (0.604)
135Antineoplastic (0.811)
Apoptosis agonist (0.639)
Chemopreventive (0.560)
Antineoplastic (myeloid leukemia) (0.545)
Antimetastatic (0.562)		Hypolipemic (0.629)
Lipid metabolism regulator (0.544)
136Antineoplastic (0.795)
Apoptosis agonist (0.625)
Prostate disorders treatment (0.605)
Antineoplastic (sarcoma) (0.574)
Chemopreventive (0.573)
Antineoplastic (myeloid leukemia) (0.538)		Hypolipemic (0.597)
Lipid metabolism regulator (0.537)		Hepatoprotectant (0.791)
137Antineoplastic (0.758)
Chemopreventive (0.661)
Prostate disorders treatment (0.654)
Apoptosis agonist (0.643)
Cytoprotectant (0.621)
Proliferative diseases treatment (0.590)
Antimetastatic (0.588)
Prostatic (benign) hyperplasia treatment (0.512)		Anti-hypercholesterolemic (0.895)
Hypolipemic (0.707)
Cholesterol synthesis inhibitor (0.549)
Atherosclerosis treatment (0.533)		Anti-eczematic (0.849)
Anti-psoriatic (0.691)
138Antineoplastic (0.758)
Chemopreventive (0.661)
Prostate disorders treatment (0.654)
Apoptosis agonist (0.643)
Cytoprotectant (0.621)
Proliferative diseases treatment (0.590)
Antimetastatic (0.588)		Anti-hypercholesterolemic (0.895)
Cholesterol synthesis inhibitor (0.549)
Atherosclerosis treatment (0.533)		Anti-eczematic (0.849)
Anti-psoriatic (0.691)
139Antineoplastic (0.809)
Cytoprotectant (0.681)
Chemopreventive (0.670)
Apoptosis agonist (0.647)
Antimetastatic (0.635)
Proliferative diseases treatment (0.635)
Prostate disorders treatment (0.632)
Antineoplastic (pancreatic cancer) (0.509)		Anti-hypercholesterolemic (0.797)
Hypolipemic (0.709)
Cholesterol synthesis inhibitor (0.557)		Anti-eczematic (0.921)
Anti-psoriatic (0.780)
140Antineoplastic (0.724)
Antimetastatic (0.695)
Apoptosis agonist (0.626)
141Antineoplastic (0.855)
Apoptosis agonist (0.637)
Antimetastatic (0.504)
142Antineoplastic (0.688)
Antineoplastic (renal cancer) (0.524)
143Apoptosis agonist (0.908)
Antineoplastic (0.857)
Chemopreventive (0.804)
Antineoplastic (liver cancer) (0.797)
Proliferative diseases treatment (0.587)
Prostate cancer treatment (0.507)		Hypolipemic (0.788)
Atherosclerosis treatment (0.625)
Cholesterol synthesis inhibitor (0.548)		Anti-eczematic (0.828)
144Antineoplastic (0.812)
Chemopreventive (0.619)
Cytoprotectant (0.558)
Antimetastatic (0.521)		Hypolipemic (0.701)Anti-inflammatory (0.862)
145Apoptosis agonist (0.870)
Antineoplastic (0.824)
Chemopreventive (0.647)		Hypolipemic (0.710)Anti-inflammatory (0.801)
146Chemopreventive (0.987)
Antineoplastic (0.858)
Anticarcinogenic (0.815)
Apoptosis agonist (0.802)
Proliferative diseases treatment (0.660)		Atherosclerosis treatment (0.640)
Anti-hypercholesterolemic (0.635)
Hypolipemic (0.511)		Hepatoprotectant (0.993)
Wound healing agent (0.872)
147Chemopreventive (0.980)
Antineoplastic (0.852)
Anticarcinogenic (0.792)
Apoptosis agonist (0.787)
Proliferative diseases treatment (0.631)		Atherosclerosis treatment (0.645)
Anti-hypercholesterolemic (0.640)		Hepatoprotectant (0.988)
Wound healing agent (0.925)
148Chemopreventive (0.969)
Antineoplastic (0.867)
Apoptosis agonist (0.801)
Anticarcinogenic (0.775)
Proliferative diseases treatment (0.625)		Atherosclerosis treatment (0.663)
Anti-hypercholesterolemic (0.611)
Hypolipemic (0.539)		Hepatoprotectant (0.987)
Wound healing agent (0.949)
* Only activities with Pa > 0.5 are shown.
Table
Table 11. Biological activities of synthetic cyclopropane-containing steroids.
Table 11. Biological activities of synthetic cyclopropane-containing steroids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
149Antineoplastic (0.891)
Apoptosis agonist (0.665)		 Antidepressant (0.954)
Psychotropic (0.919)
150Antineoplastic (0.871)
Apoptosis agonist (0.814)
Prostate disorders treatment (0.699)
Cytoprotectant (0.670)		 Antidepressant (0.961)
Psychotropic (0.953)
151Antineoplastic (0.845)Atherosclerosis treatment (0.600)Cardiovascular analeptic (0.828)
152Antineoplastic (0.827)
Prostate disorders treatment (0.723)
Prostatic (benign) hyperplasia treatment (0.619)		Anti-hypercholesterolemic (0.642)Anti-seborrheic (0.905)
153Antineoplastic (0.877)
Apoptosis agonist (0.611)		 Anti-seborrheic (0.849)
154Antineoplastic (0.864)
Prostate disorders treatment (0.731)
Prostatic (benign) hyperplasia treatment (0.652)
Prostate cancer treatment (0.564)		 Anti-seborrheic (0.844)
155Antineoplastic (0.905)
Prostate disorders treatment (0.742)
Prostatic (benign) hyperplasia treatment (0.621)		 Anti-seborrheic (0.823)
156Antineoplastic (0.791)
Cytoprotectant (0.713)
Proliferative diseases treatment (0.662)		Anti-hypercholesterolemic (0.881)
Hypolipemic (0.735)
Cholesterol synthesis inhibitor (0.641)		Anti-eczematic (0.850)
157Antineoplastic (0.744)
Prostate disorders treatment (0.677)
Cytoprotectant (0.653)
Prostatic (benign) hyperplasia treatment (0.589)		Anti-hypercholesterolemic (0.873)
Hypolipemic (0.789)
Cholesterol synthesis inhibitor (0.619)		Respiratory analeptic (0.898)
158Antineoplastic (0.851)
Apoptosis agonist (0.634)
Prostate cancer treatment (0.613)
Prostatic (benign) hyperplasia treatment (0.592)		Aldosterone antagonist (0.842)
Anti-hyperaldosteronism (0.842)		Diuretic (0.973)
Mineralocorticoid antagonist (0.956)
Antihypertensive (0.802)
159Antineoplastic (0.841)
Prostatic (benign) hyperplasia treatment (0.636)
Cytoprotectant (0.620)		 Anti-seborrheic (0.892)
160Antineoplastic (0.749)
Prostate disorders treatment (0.737)
Prostatic (benign) hyperplasia treatment (0.603)		Anti-hypercholesterolemic (0.580)Respiratory analeptic (0.765)
Cardiovascular analeptic (0.745)
161Antineoplastic (0.792)
Prostate disorders treatment (0.742)
Prostatic (benign) hyperplasia treatment (0.657)		Anti-hypercholesterolemic (0.909)
Hypolipemic (0.602)
162Antineoplastic (0.849)
Prostate disorders treatment (0.733)
Prostatic (benign) hyperplasia treatment (0.665)		Anti-hypercholesterolemic (0.666)Erythropoiesis stimulant (0.816)
163Antineoplastic (0.849)
Apoptosis agonist (0.750)
Prostate disorders treatment (0.744)
Prostate cancer treatment (0.601)		Anti-hypercholesterolemic (0.964)
Atherosclerosis treatment (0.610)		Respiratory analeptic (0.964)
Anesthetic general (0.898)
164Antineoplastic (0.714)
Cytoprotectant (0.710)
Prostate disorders treatment (0.619)		Hypolipemic (0.689)
Anti-hypercholesterolemic (0.625)		Respiratory analeptic (0.863)
Erythropoiesis stimulant (0.784)
* Only activities with Pa > 0.5 are shown.
Table
Table 12. Biological activities of cyclobutane-containing steroids and triterpenoids.
Table 12. Biological activities of cyclobutane-containing steroids and triterpenoids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
165Antineoplastic (0.754)
Chemopreventive (0.703)
Cytoprotectant (0.609)
Apoptosis agonist (0.602)
Antineoplastic (pancreatic cancer) (0.532)
Antimetastatic (0.523)
Prostate disorders treatment (0.505)		Hypolipemic (0.541)Anti-eczematic (0.905)
Anti-psoriatic (0.650)
166Antineoplastic (0.730)
Chemopreventive (0.693)
Cytoprotectant (0.608)
Apoptosis agonist (0.572)
Antimetastatic (0.517)
Antineoplastic (pancreatic cancer) (0.512)		Hypolipemic (0.571)Anti-eczematic (0.899)
Anti-psoriatic (0.650)
167Antineoplastic (0.744)
Chemopreventive (0.706)
Cytoprotectant (0.627)
Apoptosis agonist (0.526)
Antimetastatic (0.510)
Antineoplastic (pancreatic cancer) (0.503)		Hypolipemic (0.515)Anti-eczematic (0.895)
Anti-psoriatic (0.656)
168Antineoplastic (0.796)
Apoptosis agonist (0.667)
Cytoprotectant (0.621)
Chemopreventive (0.599)		Hypolipemic (0.588)
Atherosclerosis treatment (0.528)
169Antineoplastic (0.768)
Chemopreventive (0.628)
Apoptosis agonist (0.574)		Hypolipemic (0.638)
170Antineoplastic (0.780)
Apoptosis agonist (0.675)
Cytoprotectant (0.602)
Chemopreventive (0.599)		Hypolipemic (0.560)
171Antineoplastic (0.821)
Apoptosis agonist (0.740)
Chemopreventive (0.726)
Cytoprotectant (0.707)
Proliferative diseases treatment (0.553)
Prostate cancer treatment (0.551)
Antineoplastic (pancreatic cancer) (0.538)		Lipid metabolism regulator (0.794)
Anti-hypercholesterolemic (0.738)
Hypolipemic (0.709)
Cholesterol synthesis inhibitor (0.574)		Anti-secretoric (0.823)
172Antineoplastic (0.847)
Antineoplastic (myeloid leukemia) (0.624)
173Antineoplastic (0.786)
Apoptosis agonist (0.725)
Antineoplastic (sarcoma) (0.643)
Antimetastatic (0.580)
Antineoplastic (renal cancer) (0.500)		Hypolipemic (0.543)
174Antineoplastic (0.781)
Apoptosis agonist (0.722)
Antineoplastic (sarcoma) (0.635)
Antimetastatic (0.572)		Hypolipemic (0.534)
175Antineoplastic (0.897)
Chemopreventive (0.718)
Apoptosis agonist (0.658)
Antimetastatic (0.649)
Antineoplastic (renal cancer) (0.611)
Prostate cancer treatment (0.595)
Antineoplastic (pancreatic cancer) (0.547)		Hypolipemic (0.663)
176Antineoplastic (0.850)
Chemopreventive (0.847)
Apoptosis agonist (0.829)
Cytoprotectant (0.665)
Antimetastatic (0.604)
Antineoplastic (pancreatic cancer) (0.539)		Hypolipemic (0.567)
Cholesterol synthesis inhibitor (0.529)		Anti-inflammatory (0.902)
Choleretic (0.726)
177Antineoplastic (0.819)
Apoptosis agonist (0.746)		 Antiviral (Influenza) (0.647)
178Antineoplastic (0.820)
Apoptosis agonist (0.795)
Chemopreventive (0.601)
Cytoprotectant (0.594)
Antimetastatic (0.533)		Hypolipemic (0.592)Anti-inflammatory (0.826)
179Antineoplastic (0.820)
Apoptosis agonist (0.795)
Chemopreventive (0.601)
Cytoprotectant (0.594)
Antimetastatic (0.533)		Hypolipemic (0.592)Anti-inflammatory (0.826)
180Antineoplastic (0.853)
Apoptosis agonist (0.848)
Chemopreventive (0.717)
Cytoprotectant (0.636)
Antimetastatic (0.543)
Antineoplastic (myeloid leukemia) (0.523)		Hypolipemic (0.616)Anti-inflammatory (0.757)
181Antineoplastic (0.853)
Apoptosis agonist (0.848)
Chemopreventive (0.717)
Cytoprotectant (0.636)
Antimetastatic (0.543)
Antineoplastic (myeloid leukemia) (0.523)		Hypolipemic (0.616)Anti-inflammatory (0.757)
182Antineoplastic (0.772)
Apoptosis agonist (0.764)
Cytoprotectant (0.684)
Antineoplastic (multiple myeloma) (0.631)
Antineoplastic (pancreatic cancer) (0.589)
Antineoplastic (carcinoma) (0.571)
Antineoplastic (squamous cell carcinoma) (0.571)
Antimetastatic (0.565)		Hypolipemic (0.765)Anti-inflammatory (0.855)
183Antineoplastic (0.774)
Apoptosis agonist (0.730)
Cytoprotectant (0.597)
Antineoplastic (pancreatic cancer) (0.573)
Antineoplastic (multiple myeloma) (0.565)
Antineoplastic (carcinoma) (0.559)
Antineoplastic (squamous cell carcinoma) (0.559)
Antimetastatic (0.510)		Hypolipemic (0.797)
Lipid metabolism regulator (0.571)		Anti-inflammatory (0.851)
* Only activities with Pa > 0.5 are shown.
Table
Table 13. Biological activities of cyclobutane-containing steroids and triterpenoids.
Table 13. Biological activities of cyclobutane-containing steroids and triterpenoids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
184Antineoplastic (0.805)
Apoptosis agonist (0.787)
Chemopreventive (0.603)
Cytoprotectant (0.586)
Antimetastatic (0.533)		Hypolipemic (0.615)
Lipid metabolism regulator (0.511)
Anti-hypercholesterolemic (0.503)		Anti-inflammatory (0.817)
Choleretic (0.771)
185Antineoplastic (0.805)
Apoptosis agonist (0.787)
Chemopreventive (0.603)
Cytoprotectant (0.586)
Antimetastatic (0.533)		Hypolipemic (0.615)
Lipid metabolism regulator (0.511)
Anti-hypercholesterolemic (0.503)		Anti-inflammatory (0.817)
Choleretic (0.771)
186Antineoplastic (0.802)
Apoptosis agonist (0.782)
Chemopreventive (0.636)
Antimetastatic (0.547)		Hypolipemic (0.598)
Anti-hypercholesterolemic (0.515)		Anti-inflammatory (0.803)
Choleretic (0.706)
187Antineoplastic (0.802)
Apoptosis agonist (0.782)
Chemopreventive (0.636)
Antimetastatic (0.547)		Hypolipemic (0.598)
Anti-hypercholesterolemic (0.515)		Anti-inflammatory (0.803)
Choleretic (0.706)
188Antineoplastic (0.866)
Apoptosis agonist (0.671)		 Genital warts treatment (0.744)
189Antineoplastic (0.863)
Apoptosis agonist (0.584)		 Genital warts treatment (0.736)
190Antineoplastic (0.846)
Apoptosis agonist (0.553)		 Genital warts treatment (0.745)
191Antineoplastic (0.850)
Apoptosis agonist (0.577)		 Genital warts treatment (0.675)
192Antineoplastic (0.847) Genital warts treatment (0.671)
193Antineoplastic (0.844) Genital warts treatment (0.664)
194Apoptosis agonist (0.684) Genital warts treatment (0.707)
195Antineoplastic (0.845) Genital warts treatment (0.682)
196Antineoplastic (0.863) Genital warts treatment (0.736)
* Only activities with Pa > 0.5 are shown.
Table
Table 14. Bioactive natural and synthetic cyclobutane-containing steroids and triterpenoids.
Table 14. Bioactive natural and synthetic cyclobutane-containing steroids and triterpenoids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
197Antineoplastic (0.929)
Prostatic (benign) hyperplasia treatment (0.663)
Prostate cancer treatment (0.570)		Anti-hypercholesterolemic (0.696)
Immunosuppressant (0.672)
Lipid metabolism regulator (0.604)		Anti-seborrheic (0.907)
198Antineoplastic (0.784)
Apoptosis agonist (0.627)
Cytoprotectant (0.558)
Chemopreventive (0.542)		Anti-hypercholesterolemic (0.724)
Hypolipemic (0.645)		Anesthetic (0.921)
Neuroprotector (0.880)
Psychostimulant (0.675)
199Antineoplastic (0.889)
Proliferative diseases treatment (0.676)
Prostate disorders treatment (0.628)
Cytoprotectant (0.627)
Antimetastatic (0.617)
Apoptosis agonist (0.614)
Chemopreventive (0.606)
Antineoplastic (pancreatic cancer) (0.530)		Anti-hypercholesterolemic (0.902)
Hypolipemic (0.721)
Cholesterol synthesis inhibitor (0.534)		Anti-eczematic (0.911)
Choleretic (0.839)
200Antineoplastic (0.801)
Apoptosis agonist (0.706)
Proliferative diseases treatment (0.667)
Chemopreventive (0.665)
Cytoprotectant (0.616)
Antimetastatic (0.598)
Prostatic (benign) hyperplasia treatment (0.528)		Anti-hypercholesterolemic (0.932)
Hypolipemic (0.695)
Cholesterol synthesis inhibitor (0.588)		Anti-eczematic (0.871)
Choleretic (0.791)
201Antineoplastic (0.865)
Cytoprotectant (0.669)
Antineoplastic (breast cancer) (0.662)
Antineoplastic (renal cancer) (0.602)
Apoptosis agonist (0.602)
Antineoplastic (sarcoma) (0.588)
Prostate cancer treatment (0.557)
Proliferative diseases treatment (0.548)		Anti-hypercholesterolemic (0.740)
Lipid metabolism regulator (0.643)
Hypolipemic (0.613)		Anti-seborrheic (0.946)
Anti-eczematic (0.723)
202Antineoplastic (0.757)
Prostate disorders treatment (0.652)
Antineoplastic (breast cancer) (0.637)
Apoptosis agonist (0.541)		 Anti-seborrheic (0.841)
Cardiotonic (0.654)
Psychosexual dysfunction treatment (0.575)
203Antineoplastic (0.719)
Antineoplastic (breast cancer) (0.540)		Hypolipemic (0.810)Anti-seborrheic (0.818)
Cardiotonic (0.691)
204Antineoplastic (0.872)
Antineoplastic (sarcoma) (0.683)
Antineoplastic (breast cancer) (0.625)
Apoptosis agonist (0.621)
Antineoplastic (renal cancer) (0.605)
Prostate cancer treatment (0.548)
Antineoplastic (pancreatic cancer) (0.546)		Anti-hypercholesterolemic (0.616)
Lipid metabolism regulator (0.565)
Hypolipemic (0.546)		Anti-seborrheic (0.917)
Anti-secretoric (0.908)
205Antineoplastic (0.778)
Prostate disorders treatment (0.737)
Prostatic (benign) hyperplasia treatment (0.617)
Cytoprotectant (0.616)
Antimetastatic (0.571)
Proliferative diseases treatment (0.527)		Anti-hypercholesterolemic (0.638)
Hypolipemic (0.542)
Cholesterol synthesis inhibitor (0.535)		Anti-eczematic (0.831)
Anti-osteoporotic (0.799)
206Antineoplastic (0.908)
Prostate disorders treatment (0.703)
Antineoplastic (breast cancer) (0.635)
Antineoplastic (renal cancer) (0.596)
Antineoplastic (sarcoma) (0.567)
Prostate cancer treatment (0.553)
Apoptosis agonist (0.536)		 Anti-seborrheic (0.884)
Anti-osteoporotic (0.848)
207Antineoplastic (0.785)
Prostate disorders treatment (0.758)
Prostatic (benign) hyperplasia treatment (0.673)
Cytoprotectant (0.656)
Antineoplastic (sarcoma) (0.568)
Antimetastatic (0.565)
Apoptosis agonist (0.563)
Proliferative diseases treatment (0.540)
Antineoplastic (pancreatic cancer) (0.520)
Antineoplastic (breast cancer) (0.518)		Anti-hypercholesterolemic (0.813)
Hypolipemic (0.648)
Cholesterol synthesis inhibitor (0.578)		Anesthetic general (0.901)
Choleretic (0.725)
208Antineoplastic (0.832)
Prostate disorders treatment (0.740)
Apoptosis agonist (0.711)
Cytoprotectant (0.697)
Chemopreventive (0.677)
Proliferative diseases treatment (0.651)
Prostate cancer treatment (0.613)
Antineoplastic (breast cancer) (0.608)
Antineoplastic (renal cancer) (0.552)
Antineoplastic (pancreatic cancer) (0.525)		Anti-hypercholesterolemic (0.886)
Lipid metabolism regulator (0.837)
Hypolipemic (0.709)
Cholesterol synthesis inhibitor (0.605)
Atherosclerosis treatment (0.523)		Respiratory analeptic (0.969)
Neuroprotector (0.924)
Psychostimulant (0.707)
209Antineoplastic (0.839)
Chemopreventive (0.781)
Apoptosis agonist (0.722)
Proliferative diseases treatment (0.714)
Cytoprotectant (0.654)
Prostate disorders treatment (0.636)
Antimetastatic (0.591)		Anti-hypercholesterolemic (0.782)
Hypolipemic (0.702)
Cholesterol synthesis inhibitor (0.604)		Respiratory analeptic (0.949)
210Antineoplastic (0.878)
Prostate disorders treatment (0.807)
Prostate cancer treatment (0.721)
Antineoplastic (sarcoma) (0.719)
Antineoplastic (breast cancer) (0.701)
Cytoprotectant (0.631)
Apoptosis agonist (0.599)		Anti-hypercholesterolemic (0.538)Cardiovascular analeptic (0.862)
211Antineoplastic (0.845)
Prostate disorders treatment (0.648)
Antineoplastic (myeloid leukemia) (0.645)
Antineoplastic (sarcoma) (0.626)
Cytoprotectant (0.585)
Antineoplastic (breast cancer) (0.580)
Antineoplastic (renal cancer) (0.561)
Antineoplastic (carcinoma) (0.521)
Antineoplastic (squamous cell carcinoma) (0.521)		Hypolipemic (0.929)
Lipoprotein disorders treatment (0.687)		Anti-seborrheic (0.902)
212Antineoplastic (0.804)
Cytoprotectant (0.719)
Chemopreventive (0.678)
Proliferative diseases treatment (0.622)
Prostate disorders treatment (0.614)
Antimetastatic (0.596)		Anti-hypercholesterolemic (0.832)
Hypolipemic (0.820)
Cholesterol synthesis inhibitor (0.627)		Anesthetic general (0.931)
Respiratory analeptic (0.888)
* Only activities with Pa > 0.5 are shown.
Table
Table 15. Biological activities of synthetic cyclobutane-containing steroids.
Table 15. Biological activities of synthetic cyclobutane-containing steroids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
213Antineoplastic (0.891) Male reproductive disfunction treatment (0.923)
Aromatase inhibitor (0.717)
214Antineoplastic (0.909)
Prostatic (benign) hyperplasia treatment (0.663)
Prostate cancer treatment (0.570)		Anti-hypercholesterolemic (0.696)
Lipid metabolism regulator (0.604)		Anti-seborrheic (0.914)
Respiratory analeptic (0.756)
215Antineoplastic (0.860)
Prostate disorders treatment (0.717)
Prostatic (benign) hyperplasia treatment (0.621)		 Ovulation inhibitor (0.794)
Neuroprotector (0.716)
216Antineoplastic (0.805)
Prostatic (benign) hyperplasia treatment (0.591)		Hepatic disorders treatment (0.601)
Anti-hypercholesterolemic (0.589)		Respiratory analeptic (0.871)
Anti-inflammatory (0.837)
217Antineoplastic (0.805)
Prostatic (benign) hyperplasia treatment (0.591)		Anti-hypercholesterolemic (0.592)Respiratory analeptic (0.874)
Anti-inflammatory (0.839)
218Antineoplastic (0.736)
Prostate disorders treatment (0.589)		Anti-hypercholesterolemic (0.582)
Atherosclerosis treatment (0.534)		Anti-seborrheic (0.915)
Alopecia treatment (0.893)
219Antineoplastic (0.750)
Prostate disorders treatment (0.713)
Prostatic (benign) hyperplasia treatment (0.501)		 Anti-seborrheic (0.917)
Anti-osteoporotic (0.904)
220Antineoplastic (0.786)
Apoptosis agonist (0.567)		 Anti-seborrheic (0.924)
Anti-osteoporotic (0.752)
221Antineoplastic (0.854)
Proliferative diseases treatment (0.588)
Antimetastatic (0.552)		Hypolipemic (0.832)
Anti-hypercholesterolemic (0.635)
Cholesterol synthesis inhibitor (0.612)		Anti-eczematic (0.814)
Anti-osteoporotic (0.657)
* Only activities with Pa > 0.5 are shown.
Table
Table 16. Biological activities of steroids containing additional 5-membered ring in molecule.
Table 16. Biological activities of steroids containing additional 5-membered ring in molecule.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
222Antineoplastic (0.783)
Prostate disorders treatment (0.679)
Cytoprotectant (0.622)
Apoptosis agonist (0.607)
Antineoplastic (sarcoma) (0.603)
Prostatic (benign) hyperplasia treatment (0.519)
Antimetastatic (0.514)
Antineoplastic (pancreatic cancer) (0.509)		Hypolipemic (0.551)Anti-inflammatory (0.778)
223Antineoplastic (0.813)
Apoptosis agonist (0.683)
Prostate disorders treatment (0.654)
Antineoplastic (sarcoma) (0.593)
Antineoplastic (pancreatic cancer) (0.541)		 Anti-inflammatory (0.775)
Antiprotozoal (Plasmodium) (0.622)
224Antineoplastic (0.787)
Prostate disorders treatment (0.685)
Apoptosis agonist (0.629)
Antineoplastic (sarcoma) (0.589)
Prostatic (benign) hyperplasia treatment (0.550)
Antineoplastic (pancreatic cancer) (0.506)		 Anti-inflammatory (0.829)
Antiprotozoal (Plasmodium) (0.625)
225Antineoplastic (0.931)
Apoptosis agonist (0.899)
Antineoplastic enhancer (0.537)
Cytostatic (0.519)
Antineoplastic (genitourinary cancer) (0.512)		 Cardiotonic (0.763)
Immunosuppressant (0.683)
226Apoptosis agonist (0.876)
Antineoplastic (0.873)
Antineoplastic (genitourinary cancer) (0.530)		 Inflammatory Bowel disease treatment (0.704)
Immunosuppressant (0.681)
227Antineoplastic (0.885)
Apoptosis agonist (0.824)
Antineoplastic (genitourinary cancer) (0.550)
Antimetastatic (0.513)		 Cardiotonic (0.698)
228Antineoplastic (0.878)
Apoptosis agonist (0.861)
Chemopreventive (0.717)
Proliferative diseases treatment (0.581)		Anti-hypercholesterolemic (0.808)
Hypolipemic (0.788)
Atherosclerosis treatment (0.534)		Immunosuppressant (0.813)
229Antineoplastic (0.668) Respiratory analeptic (0.874)
230Antineoplastic (0.735)
Apoptosis agonist (0.545)		 Anti-inflammatory (0.604)
231Antineoplastic (0.846)
Cytostatic (0.771)
Apoptosis agonist (0.613)
Antineoplastic (sarcoma) (0.526)		 Hepatic disorders treatment (0.977)
Macular degeneration treatment (0.882)
232Antineoplastic (0.788)
Apoptosis agonist (0.645)		 Hepatic disorders treatment (0.937)
Antiprotozoal (Plasmodium) (0.820)
233Antineoplastic (0.709)
Apoptosis agonist (0.632)		 Anti-eczematic (0.636)
234Antineoplastic (0.840)
Apoptosis agonist (0.749)		 Cardiotonic (0.572)
235Antineoplastic (0.840)
Apoptosis agonist (0.749)		 Anti-inflammatory (0.637)
236Apoptosis agonist (0.814)
Antineoplastic (0.647)
Cytoprotectant (0.613)
Chemopreventive (0.564)
Prostate disorders treatment (0.564)		Anti-hypercholesterolemic (0.578)
Hypolipemic (0.546)
Cholesterol synthesis inhibitor (0.534)		Anti-inflammatory (0.716)
* Only activities with Pa > 0.5 are shown.
Table
Table 17. Biological activities of Bioactive cyclopentane- and cyclohexane-containing steroids and triterpenoids.
Table 17. Biological activities of Bioactive cyclopentane- and cyclohexane-containing steroids and triterpenoids.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
237Antineoplastic (0.761)
Prostate disorders treatment (0.755)
Prostatic (benign) hyperplasia treatment (0.683)		Anti-hypercholesterolemic (0.829)
Hypolipemic (0.756)
Atherosclerosis treatment (0.632)		Anesthetic general (0.901)
Respiratory analeptic (0.884)
238Antineoplastic (0.830)
Prostatic (benign) hyperplasia treatment (0.532)		 Antiprotozoal (0.781)
Cardiotonic (0.773)
239Antineoplastic (0.820)
Prostate disorders treatment (0.784)
Prostatic (benign) hyperplasia treatment (0.684)
Prostate cancer treatment (0.627)		 Cardiovascular analeptic (0.913)
240Antineoplastic (0.910)
Apoptosis agonist (0.765)
Cytoprotectant (0.593)
Prostate cancer treatment (0.538)		 Cardiovascular analeptic (0.888)
241Antineoplastic (0.765)
Prostatic (benign) hyperplasia treatment (0.653)
Cytoprotectant (0.641)		Anti-hypercholesterolemic (0.824)
Hypolipemic (0.686)
Atherosclerosis treatment (0.629)		Anti-eczematic (0.862)
Anti-osteoporotic (0.826)
Antiparkinsonian, rigidity relieving (0.625)
242Antineoplastic (0.803)
Prostatic (benign) hyperplasia treatment (0.617)
Prostate cancer treatment (0.518)		Neurodegenerative diseases treatment (0.642)Anti-osteoporotic (0.972)
Anti-psoriatic (0.884)
243Antineoplastic (0.797)
Prostate disorders treatment (0.680)
Prostatic (benign) hyperplasia treatment (0.551)		Alzheimer’s disease treatment (0.750)Anti-osteoporotic (0.965)
Anti-seborrheic (0.891)
Anti-psoriatic (0.864)
244Antineoplastic (0.775)
Prostate disorders treatment (0.706)
Cytoprotectant (0.638)
Prostatic (benign) hyperplasia treatment (0.624)
Apoptosis agonist (0.620)		Anti-hypercholesterolemic (0.772)
Hypolipemic (0.617)		Anti-eczematic (0.846)
Anti-osteoporotic (0.787)
245Antineoplastic (0.777)
Cytoprotectant (0.689)
Prostate disorders treatment (0.677)
Prostatic (benign) hyperplasia treatment (0.581)		Anti-hypercholesterolemic (0.866)
Hypolipemic (0.705)
Cholesterol synthesis inhibitor (0.588)		Anti-eczematic (0.840)
Anti-osteoporotic (0.792)
246Antineoplastic (0.918)
Aromatase inhibitor (0.903)
Apoptosis agonist (0.894)
Prostate disorders treatment (0.699)
Prostatic (benign) hyperplasia treatment (0.597)
Cytoprotectant (0.597)		Anti-hypercholesterolemic (0.674)
Hypolipemic (0.622)		Anti-eczematic (0.907)
247Antineoplastic (0.943)
Prostate disorders treatment (0.705)
Prostatic (benign) hyperplasia treatment (0.601)
Apoptosis agonist (0.596)		 Neuroprotector (0.734)
Immunosuppressant (0.650)
248Antineoplastic (0.937)
Aromatase inhibitor (0.903)
Prostate disorders treatment (0.697)
Prostatic (benign) hyperplasia treatment (0.591)		 Neuroprotector (0.735)
Immunosuppressant (0.654)
249Antineoplastic (0.902)
Prostate disorders treatment (0.740)
Prostatic (benign) hyperplasia treatment (0.662)
Prostate cancer treatment (0.569)		 Cardiovascular analeptic (0.854)
Anesthetic (0.698)
Cardiotonic (0.605)
250Antineoplastic (0.892)
Apoptosis agonist (0.710)
Prostate disorders treatment (0.662)
Prostatic (benign) hyperplasia treatment (0.541)		 Anti-osteoporotic (0.972)
251Antineoplastic (0.742)
Prostate disorders treatment (0.726)
Prostatic (benign) hyperplasia treatment (0.662)		Anti-hypercholesterolemic (0.622)Neuroprotector (0.734)
Immunosuppressant (0.705)
252Antineoplastic (0.769)
Prostate disorders treatment (0.753)
Prostatic (benign) hyperplasia treatment (0.663)		 Anticonvulsant (0.733)
Neuroprotector (0.727)
253Antineoplastic (0.810)
Prostate disorders treatment (0.726)
Prostatic (benign) hyperplasia treatment (0.647)		Anti-hypercholesterolemic (0.705)Immunosuppressant (0.764)
Neuroprotector (0.749)
254Antineoplastic (0.754) Antiprotozoal (Plasmodium) (0.648)
255Antineoplastic (0.774)
Cytoprotectant (0.633)
Prostate disorders treatment (0.572)		Hypolipemic (0.766)
Anti-hypercholesterolemic (0.652)
Cholesterol synthesis inhibitor (0.615)
256Antineoplastic (0.858)
Proliferative diseases treatment (0.604)
Apoptosis agonist (0.583)
Cytoprotectant (0.561)
Antimetastatic (0.549)
Prostate disorders treatment (0.535)		Hypolipemic (0.838)
Anti-hypercholesterolemic (0.611)
Cholesterol synthesis inhibitor (0.601)
257Antineoplastic (0.694)
Prostate disorders treatment (0.621)
Antineoplastic (breast cancer) (0.572)		 Anti-seborrheic (0.928)
Cardiovascular analeptic (0.674)
258Antineoplastic (0.854)
Prostatic (benign) hyperplasia treatment (0.621)		Anti-hypercholesterolemic (0.682)
Neuroprotector (0.756)
Acute neurologic disorders treatment (0.741)
259Antineoplastic (0.845)
Apoptosis agonist (0.654)
Prostatic (benign) hyperplasia treatment (0.585)		Hypolipemic (0.548)Cardiotonic (0.917)
Antiarrhythmic (0.809)
260Antineoplastic (0.823)
Prostate disorders treatment (0.746)
Prostatic (benign) hyperplasia treatment (0.615)		 Anesthetic general (0.841)
261Antineoplastic (0.715)
Prostate disorders treatment (0.701)
Prostatic (benign) hyperplasia treatment (0.619)		 Anesthetic general (0.712)
262Antineoplastic (0.834)Anti-hypercholesterolemic (0.794)Anesthetic general (0.805)
263Antineoplastic (0.796)
Apoptosis agonist (0.723)
Prostate disorders treatment (0.676)		Anti-hypercholesterolemic (0.527)Anti-osteoporotic (0.934)
Anti-seborrheic (0.918)
264Antineoplastic (0.757)
Prostate disorders treatment (0.658)
Apoptosis agonist (0.550)
Prostatic (benign) hyperplasia treatment (0.503)		 Spasmolytic, urinary (0.961)
* Only activities with Pa > 0.5 are shown.
Table
Table 18. Bioactive synthetic steroids containing an additional 5- or 6-membered ring in molecule.
Table 18. Bioactive synthetic steroids containing an additional 5- or 6-membered ring in molecule.
No.Antitumor & Related Activity, (Pa) *Lipid Metabolism Regulators, (Pa) *Additional Predicted Activity, (Pa) *
265Antineoplastic (0.933)
Apoptosis agonist (0.667)		 Antimitotic (0.843)
266Antineoplastic (0.942)
Apoptosis agonist (0.619)
Antineoplastic (sarcoma) (0.510)		 Antimitotic (0.848)
267Antineoplastic (0.934)
Apoptosis agonist (0.890)
Cytostatic (0.688)
Antineoplastic (sarcoma) (0.647)
T cell inhibitor (0.608)
Prostate disorders treatment (0.606)
Antineoplastic (pancreatic cancer) (0.573)		 Antimitotic (0.829)
Antiprotozoal (Plasmodium) (0.650)
268Antineoplastic (0.936)
Apoptosis agonist (0.720)
Antimetastatic (0.515)
Antineoplastic (pancreatic cancer) (0.504)		 Antimitotic (0.849)
269Antineoplastic (0.922)
Apoptosis agonist (0.641)
Antimetastatic (0.515)		 Antimitotic (0.819)
Antiprotozoal (Plasmodium) (0.694)
270Antineoplastic (0.929)
Apoptosis agonist (0.669)
Antineoplastic (renal cancer) (0.570)		 Antimitotic (0.853)
271Antineoplastic (0.930)
Apoptosis agonist (0.753)
Cytostatic (0.735)
Antineoplastic (renal cancer) (0.603)
Antineoplastic (sarcoma) (0.602)
Antineoplastic (pancreatic cancer) (0.551)
Antineoplastic (lymphocytic leukemia) (0.548)
Antineoplastic (myeloid leukemia) (0.529)
Antineoplastic (genitourinary cancer) (0.523)		 Antimitotic (0.776)
Immunosuppressant (0.665)
272Antineoplastic (0.933)
Apoptosis agonist (0.805)
Antimetastatic (0.535)
Antineoplastic (pancreatic cancer) (0.524)		 Antimitotic (0.808)
Immunosuppressant (0.745)
273Antineoplastic (0.934)
Apoptosis agonist (0.805)
Antineoplastic (sarcoma) (0.530)
Antineoplastic (pancreatic cancer) (0.524)		 Antimitotic (0.804)
Immunosuppressant (0.731)
Antiprotozoal (Plasmodium) (0.668)
274Antineoplastic (0.875)
Apoptosis agonist (0.728)
Chemopreventive (0.693)
Prostate disorders treatment (0.670)
Proliferative diseases treatment (0.659)
Anticarcinogenic (0.630)
Antineoplastic (breast cancer) (0.551)
Antineoplastic (pancreatic cancer) (0.540)
Prostatic (benign) hyperplasia treatment (0.526)
Antineoplastic (sarcoma) (0.517)		Anti-hypercholesterolemic (0.858)
Hypolipemic (0.767)
Cholesterol synthesis inhibitor (0.608)
Atherosclerosis treatment (0.600)
Lipid metabolism regulator (0.590)		Anti-ischemic, cerebral (0.932)
Antiprotozoal (Leishmania) (0.559)
275Chemopreventive (0.966)
Apoptosis agonist (0.896)
Antineoplastic (0.866)		Hypolipemic (0.575)
276Chemopreventive (0.958)
Apoptosis agonist (0.842)
T cell inhibitor (0.620)		Hypolipemic (0.540)
* Only activities with Pa > 0.5 are shown.
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MDPI and ACS Style

Dembitsky, V.M.; Gloriozova, T.A.; Poroikov, V.V. Antitumor Profile of Carbon-Bridged Steroids (CBS) and Triterpenoids. Mar. Drugs 2021, 19, 324. https://doi.org/10.3390/md19060324

AMA Style

Dembitsky VM, Gloriozova TA, Poroikov VV. Antitumor Profile of Carbon-Bridged Steroids (CBS) and Triterpenoids. Marine Drugs. 2021; 19(6):324. https://doi.org/10.3390/md19060324

Chicago/Turabian Style

Dembitsky, Valery M., Tatyana A. Gloriozova, and Vladimir V. Poroikov. 2021. "Antitumor Profile of Carbon-Bridged Steroids (CBS) and Triterpenoids" Marine Drugs 19, no. 6: 324. https://doi.org/10.3390/md19060324

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