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Molecules 2018, 23(9), 2333; doi:10.3390/molecules23092333

Review
Chemical Constituents from Croton Species and Their Biological Activities
Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming 650224, China
*
Author to whom correspondence should be addressed.
Received: 18 July 2018 / Accepted: 10 September 2018 / Published: 12 September 2018

Abstract

:
The genus Croton belongs to the Euphorbiaceae family, which comprises approximately 1300 species. Many Croton species have been used as folk medicines. This review focuses on the chemical constituents from Croton species and their relevant biological activities, covering the period from 2006 to 2018. A total of 399 new compounds, including 339 diterpenoids, were reported. Diterpenoids are characteristic components of the Croton species. These isolated compounds exhibited a broad spectrum of bioactivities, including cytotoxic, anti-inflammatory, antifungal, acetylcholinesterase inhibitory, and neurite outgrowth-promoting properties. The present review provides a significant clue for further research of the chemical constituents from the Croton species as potential medicines.
Keywords:
Croton species; phytochemistry; biological activities; diterpenoids; cytotoxicity

1. Introduction

The genus Croton belongs to the Euphorbiaceae family, and contains approximately 1300 species of trees, shrubs, and herbs, which are widely distributed throughout tropical and subtropical regions of the world. Many Croton species have been used as folk medicines in Africa, south Asia, and south America, for the treatment of many diseases such as stomachache, abscesses, inflammation, and malaria [1,2,3]. The seeds of C. tiglium, which are well-known as “badou”, had been utilized as a traditional Chinese medicine to treat gastrointestinal disorders, intestinal inflammation, and rheumatism. The roots of C. crassifolius, known as “jiguxiang” in China, are mainly used as a traditional medicine for the treatment of stomachache and sore throat [3]. The genus Croton is abundant in diverse diterpenoids, including clerodane, tigliane, kaurane, labdane, cembrane, and pimarane, with a wide range of biological activities, such as cytotoxic, anti-inflammatory, and anti-microbial [1,2,3,4,5]. Due to their great structural diversity and broad relevant bioactivities, Croton species have attracted increasing research attention. Several authors have provided reviews about the chemical constituents and biological activities of Croton species. A review came out in 2006 regarding clerodane diterpenes isolated from Croton species, their 13C-NMR spectroscopic data, and biological activities [2]. In 2007, a comprehensive review on the traditional uses, chemistry, and pharmacology of Croton species was published [1]. In 2013, anticancer and antioxidant activities of extracts and pure compounds from several Croton species were reviewed [4]. Five review articles were published in recent years which focused on ethnopharmacological uses, phytochemistry, and pharmacology of a single Croton species [6,7,8,9,10]. In the last decade, there has been a dramatic progress in the chemical constituents and relevant biological activities of Croton species. However, so far, no comprehensive review has been published since 2007. In the present review, we summarize systematically the research advances on the new chemical constituents and their biological activities of Croton species reported in the literature, as found on Web of Science, Google Scholar, PubMed, and SciFinder, from 2006 to March 2018, with the aim of providing a basis for further research of natural product drug discovery.

2. Chemical Constituents

To date, 399 new compounds have been isolated and identified from Croton species, including 339 diterpenoids (1339), seven sesquiterpenoids (340346), one sesterterpenoid (347), one triterpenoid (348), 21 glycosides (349369), eight alkaloids (370377), three benzoate derivatives (378380), three pyran-2-one derivatives (381383), two cyclopeptide (384, 385), two tropone derivatives (386, 387), two limonoids (388, 389), and ten miscellaneous compounds (390399). Their structures, molecular formula, names, corresponding sources, and references are summarized in Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Figure 12 and Figure 13 and Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13, Table 14, Table 15, Table 16, Table 17, Table 18, Table 19, Table 20, Table 21, Table 22, Table 23, Table 24, Table 25, Table 26 and Table 27.

2.1. Diterpenoids

Phytochemical investigations on Croton species revealed the predominant secondary metabolites as diterpenoids, including clerodane, tigliane, kaurane, crotofolane, labdane, cembrane, abietane, casbane, halimane, pimarane, cleistanthane, grayanane, atisane, phytane, and laevinane diterpenoids. Three hundred & thirty-nine new diterpenoids (1339) were reported from Croton species.

2.1.1. Clerodanes

Ninety-two new clerodane diterpenoids (192) were isolated from Croton species, including two clerodane diterpenoid with acyclic at C-9s, eight clerodane diterpenoids with butenolide at C-9, and 82 furan-clerodane diterpenoids [11]. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 1 and Table 1. Two new clerodane diterpenoids with acyclic side chain at C-9, ent-3,13E-clerodadiene-15-formate (1) and 3α,4α,15,16-tetrahydroxy-ent-neo-cleroda-13E-ene (45), were isolated from the roots of C. sylvaticus [12] and the roots of C. limae [13], respectively. Eight new clerodane diterpenoids with butenolide at C-9 (2, 3, 5, 13, 14, 75, 91, 92) were obtained from three Croton species (C. crassifolius, C. glabellus, and C. oligandrus) [14,15,16,17,18]. Furan-clerodane diterpenoids are abundant in Croton species, and 82 new ones were isolated from different Croton species. For example, Centrafricine I (4) from C. mayumbensis was a new furan-clerodane diterpenoid with a 6, 18-γ-lactone ring [19]. Two novel rearranged ent-clerodane diterpenoids Laevinoids A, B (21, 22) containing an unusual 3/5 bicyclic ring were obtained from the branches and leaves of C. laevigatus; 22 represents the first chlorinated example of the clerodane family [20]. Compounds (2327) bearing a C-19/C-20 six-membered ring were identified from C. laui [21]. Phytochemical investigations on three Croton species (C. oblongifolius, C. yanhuii, and C. hypoleucus) afforded six new furan-clerodanoids (12, 36, 37, 8486) with a 3,4-epoxy moiety [22,23,24]. Crotoeurins A–C (4042) were found from the twigs and leaves of C. euryphyllus. Among them, crotoeurin A (40) was a nor-clerodane diterpenoid dimer with a unique cyclobutane ring via a [2 + 2] cycloaddition [25]. Three new furan-clerodane diterpenoids, cracroson A–C (4648) were obtained from C. crassifolius, while cracroson C (48) represents the first example of a clerodane diterpenoid alkaloid [26]. Twelve new ent-clerodanoids (55, 66) were isolated from the roots of C. megalocarpoides. Among them, compounds (5866) possessed 9, 12-γ-lactone ring [27]. Investigation on the roots of C. crassifolius afforded eight new clerodanoids, crassins A−H (6875). Among them, crassins A–B (68, 69) represents ring B rearranged clerodanoids, whereas crassins C (70) was ring A rearranged one [17]. One new nor-clerodane diterpenoid, norcrassifolin (83), with a 1,12-lactone six-membered ring, was isolated from C. crassifolius [28].

2.1.2. Tiglianes

Fifty-six new tigliane diterpenoids (93148) were reported from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 2 and Table 2. Investigations on the aerial parts of C. ciliatoglandulifer produced four new tiglianoids (9598). Among them, tiglianoids (9597) possess a N,N-dimethyl moiety at 2′position [41]. Alienusolin (107) and compound (111) were obtained from the roots and the leaves of C. alienus and the leaves of C. mauritianus, respectively [42,43]. The twigs and leaves of C. caudatus produced three new tiglianoids, crotusins A–C (128130) [44]. Tigliane diterpenoids were abundant in C. tiglium, other 47 new ones (93, 94, 99106, 108110, 112127, 131148) were isolated from C. tiglium [45,46,47,48,49,50,51,52]. Among them, compound (112) was the first tiglianoid with the C20-aldehyde group [48].

2.1.3. Kauranes

Fourty new kaurane diterpenoids (149188) were found from Croton species. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 3 and Table 3. Five new 3,4-seco ent-kauranes (149150, 160161, 168) were isolated from C. caracasana [53], C. megistocarpus [54], and C. oblongifolius [55], respectively. Investigations on C. kongensis afforded eight new 8,9-seco-ent-kaurane diterpenes (151–154, 156, 178180) [56,57,58,59]. Compound 181, one new kaurane bearing a monoterpene unit at C-16, was found from C. limae [35]. From the stems of C. micans, five new 3,4-seco-ent-kaurene dimers (182186) were isolated [60], while other two dimeric ent-kaurane diterpenoids (187188) were elucidated from C. tonkinensis [61].

2.1.4. Crotofolanes

Thirty-nine new crotofolane diterpenoids (189227) were obtained from Croton species. Their structures, molecular formula, names, corresponding sources, and references are summarized in Figure 4 and Table 4. Twenty-four new crotofolane diterpenoids (189198, 212222, 225227) were isolated from C. caracasanus [68,69,70,71]. Among them, three new crotofolane diterpenoid alkaloids, cascarinoids A–C (225227), were firstly found. Investigations on C. argyrophyllus gave four new crotofolanes (199202) [72]. Crotocarasin A–D (203206) were isolated from the stems of C. caracasanus [73]. Five new 1, 14-seco-crotofolanes from C. insularis were obtained [74], while C. dichogamus yielded crotodichogamoin A–B (223224) [75].

2.1.5. Labdanes

Thirty-six new labdane diterpenoids (228263) were isolated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 5 and Table 5 12 new labdanes (228, 249259) were isolated from C. laui [21,76,77]. From the leaves of C. stipuliformis, three 3,4-seco-ent-labdanes (229231) and one ent-labdane (232) were obtained [78]. Investigation of C. laevigatus led to the isolation of 16 new labdanes (233248). Among them, crotonlaevins A–B (233, 234), represents rare labdanes with a dodecahydronaphtho [1,2-c] furan moiety [79]. Three new labdane diterpenoids (260262) were found from C. jacobinensis [77] and C. decalvatus [80], respectively. Bicrotonol A (263), one dimeric labdane-type diterpenoid, was obtained from the roots of C. crassifolius [81].

2.1.6. Cembranes

A total of 28 new cembrane diterpenoids (264291) were obtained from Croton species. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 6 and Table 6. launine O-P (264, 265), two new cembranes, were reported from the aerial parts of C. laui [76]. Investigations on the stem bark of C. oblongifolius afforded four new furanocembranoids (266269) [83]. laevigatlactones A–F (270275), six new cembranoids possessing a rare six-membered lactone moiety attached to C-1 and C-20, were firstly isolated from C. laevigatus [84]. 14 new cembranoids (276289) were found from C. gratissimus [85,86]. Among them, compound 276 was first example of a 2,12-cyclocembranolide. The leaves of C. longissimus produced two new cembranes (290, 291) [87].

2.1.7. Abietanes

Fourteen new abietane diterpenoids (292305) were isolated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 7 and Table 7. Two new abietanes (292, 293) were obtained from C. megalocarpoides [27], and C. argyrophylloides [63], respectively. Investigation of C. caudatus led to the isolation of 5 new abietanes (294298). Among them, crotontomentosin A (294) was a 9,10-seco abietane [88]. Crotolaevigatones A–G (299305), 7 new abietanes were found from the twigs and leaves of C. laevigatus, and compounds (304, 305) possessed a 9,13-epidioxy moiety [89].

2.1.8. Casbanes

Seven new casbane diterpenoids (306312) were found from Croton species. Their structures, molecular formula, names, corresponding sources, and references are summarized in Figure 8 and Table 8. Five new casbane s (306310) were reported from C. nepetaefolius [90], and C. argyrophyllus [72,91], respectively. Investigations on the stem bark of C. insularis afforded two new casbanes, EBC-324 (311) and EBC-329 (312). Among them, EBC-329 (312) represented the first natural seco-casbane diterpene, while EBC-324 (311) was the first endoperoxide casbane [92].

2.1.9. Halimanes

Six new halimane diterpenoids (313318) were reported from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 8 and Table 9. Investigations on the stem bark of C. oblongifolius afforded two new cleistanthanes (325, 326). Among them, compound 326 was a 3,4-seco cleistanthane [93]. One new bis-nor-cleistanthane diterpenoid (327), was found from the twigs and leaves of C. caudatus [94].

2.1.10. Pimaranes

Six new pimarane diterpenoids (319324) were obtained from Croton species. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 8 and Table 10. All six new pimaranes (319324) were isolated from C. insularis [96,97]. Among them, compound 319 was an important biosynthetic intermediate.

2.1.11. Cleistanthanes

Three new cleistanthane diterpenoids (325327) were ioslated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 8 and Table 11. Investigations on the stem bark of C. oblongifolius afforded two new cleistanthanes (325, 326). Among them, compound 326 was a 3,4-seco cleistanthane [93]. One new bis-nor-cleistanthane diterpenoid (327), was found from the twigs and leaves of C. caudatus [94].

2.1.12. Grayananes, Atisanes, Phytanes, Laevinanes and Meroditerpenoids

From the leaves of C. tonkinensis, two new rare grayanane diterpenoids, crotonkinensins A (328) and B (329), were isolated [100]. Two new 3,4-seco atisane diterpenoids, crotobarin (330) from C. barorum and crotogoudin (331) from C. goudotii, were found [101]. Investigations on the aerial parts of C. laui gave two new phytane diterpenoids (332, 333) [37]. Two new laevinane diterpenoids, crolaevinoid G (334) and H (335), were obtained [39]. Two new meroditerpenoids, steenkrotin A (336) and B (337), containing new carbon skeletons, were isolated from the leaves of C. steenkampianus [102]. From the the roots of C. crassifolius, two new meroditerpenoids, norcrassin A (338) and cracroson D (339), were reported [35,69]. Among them, norcrassin A (338) possessing a new carbon skeleton with a 5/5/5/6 tetracyclic system, was a C16 tetranorditerpenoid, while cracroson D (339) featured a new skeleton with a rare cyclobutane ring. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 9 and Table 12, Table 13, Table 14, Table 15 and Table 16.

2.2. Sesquiterpenoids, Sesterterpenoids and Triterpenoids

Seven new sesquiterpenoids (340346), one sesterterpenoid (347) and one triterpenoid (348) were ioslated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are summarized in Figure 10 and Table 17, Table 18 and Table 19. From C. muscicarpa, one new patchoulane sesquiterpenoid (340) was obtained [103]. A guaiane sesquiterpenoid (341) was isolated from C. regelianus [94]. Investigations on the leaves of C. pedicellatus afforded a bis-nor-sesquiterpenoid (342) [104]. Two rare sesquiterpenoid, Crocrassins A (343) and B (344) having cyclopropylcyclopentane moiety, were reported [105]. Other two sesquiterpenoids, 1,3,5-cadinatriene-(7R,10S)-diol (345) and cracroson H (346) were found from C. dichogamus [75], and C. crassifolius [40], respectively. One rare sesterterpenoid, pseudopulchellol (347), was isolated from the leaves of C. pseudopulchellus [106]. From the root of C. bonplandianum, a new ursane triterpenoid (348) was obtained [107].

2.3. Glycosides

Twenty-one new glycosides (349369) were ioslated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 11 and Table 20. From C. crassifolius, a patchoulane sesquiterpenoid glycoside (349), an isocrotofolane glucoside (368), and a phenolic glycoside (369) were reported [69,108]. Compound 350, isolated from C. lachnocarpus, was the first triterpenoid glucoside reported from the genus Croton [109]. A new flavone glucoside (351) was found from the leaves of C. zambesicus [110]. Investigations on the leaves of C. cascarilloides and C. oblongifolius afforded 13 new megastigmane glycosides, crotonionosides A–G (352358) and Oblongionosides A–F (359364) [111,112]. One new bis-nor-sesquiterpenoid glycoside (365) was isolated from C. pedicellatus [104]. One new diglyceride galactoside (366) and one new clerodane glucoside (367) were obtained from C. sparsiorus [113], and C. limae [35], respectively.

2.4. Alkaloids

Eight new alkaloids (370377) were reported from Croton species. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 12 and Table 21. From C. sparsiflorus, two new amide alkaloids crotamides A (370) and B (371), and one new proaporphine alkaloid, crotsparsidine (374) were isolated [96,114]. One new pyrazine derivative, crotonine (372) was obtained from the leaves of C. tiglium [97]. Investigations on C. cascarilloides afforded a new glutarimide alkaloid, crotonimide C (375) [42]. Other three new alkaloids (373, 376377) were found from C. pullei, C. heliotropiifolius, and C. echioides, respectively [115,116,117].

2.5. Benzoate Derivatives, Pyran-2-One Derivatives, Cyclicpeptides, Tropone Derivatives and Limonoids

Three benzoate derivatives (378380) were isolated from C. sylvaticus and C. hutchinsonianus [118,119]. Investigations on C. crassifolius afforded three new pyran-2-one derivatives, crotonpyrone A (381), B (382) and C (383) [120,121]. Two cyclicpeptides (384, 385) were obtained from C. gossypifolius and C. urucurana [122,123], while two tropone derivatives (386, 387) were isolated from C. zehntneri and C. argyroglossum [124,125]. From the root bark of C. jatrophoides, two new limonoids, musidunin (388) and musiduol (389), were found [126]. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 13 and Table 22, Table 23, Table 24, Table 25 and Table 26.

2.6. Miscellaneous Compounds

Flavonoids, lignans, and other types of 10 compounds were also isolated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 13 and Table 27. From the stems of C. caudatus, one new flavone, crotoncaudatin (390), was isolated [127]. A new nor-lignan (391) was obtained from the twigs and leaves of C. kongensis [67]. Investigations on C. laevifolius gave two new prenylated dihydrostilbenes, laevifolin A (393), B (394) and one new aromatic compound (399) [89,128]. A long chain linear ester, lobaceride (392) was isolated from the twigs and leaves of C. lobatus [129]. One indanone derivative (395) was found from the leaves of C. steenkampianus [102], while a trisubstituted furan derivative (396) was isolated from the bark of C. oblongifolius [22]. From C. sparsiflorus, an inositol, sparsifol (397), and a sphingolipid, sparsioamide (398), were obtained [96,113].

3. Biological Activities

Compounds isolated from Croton species exert a wide range of biological activities, including cytotoxic, anti-inflammatory, antifungal, acetylcholinesterase inhibitory, and neurite outgrowth-promoting activities.

3.1. Cytotoxic Activity

The anti-tumor activity of many plants from the Croton species have been reported. Therefore, the cytotoxicity of the isolated compounds is the most commonly studied bioactivity. The cytotoxic activities of the isolated compounds from the Croton species are listed in Table 28. Four new tigliane diterpene esters (135137, 139) from the leaves of C. tiglium, exhibited most potent cytotoxic activity against K562 cell line with IC50 values of 0.03, 0.03, 0.07 and 0.05 μM, respectively [51].

3.2. Anti-Inflammatory Activity

Bioassay-guided fractionation of the aerial parts of C. ciliatoglandulifer led to the isolation of tigliane diterpenoids 95, 97, which inhibited the enzymes cyclooxygenases-1 (IC50, 0.001, and 1.0 μM, respectively) and cyclooxygenases-2 (IC50, 2.2 μM, for compound 95) [41]. A tigliane diterpenoid (114) was isolated from the branches and leaves of C. tiglium, which displayed moderate inhibition of the enzymes COX-1 and COX-2, with IC50 values of 0.14 and 8.5 μM, respectively [48]. crotonkinin A (157), isolated from C. tonkinensis, showed anti-inflammatory effect on LPS-induced iNOS-dependent NO production and NOX-dependent ROS production in microglial cells (IC50, 46.2 ± 3.1 μM in NOS; maximum inhibition of NOX activity at 50 μM, 11.2%) [62]. Eight ent-kauranes (169176) from C. tonkinensis exhibited the anti-inflammatory potential for inhibition of superoxide Anion generation and elastase release. Among them, crotonkinins F (172) displayed significant inhibition of superoxide anion generation (IC50, 2.88 ± 0.52 μM) and elastase release (IC50, 4.44 ± 1.45 μM) [66]. Labdane diterpenoids 251, 254 and 257, 258, isolated from the aerial parts of C. laui, were found to show anti-inflammatory activities in LPS-stimulated RAW 264.7 cells with IC50 values in the range 42.73–93.04 μM [82]. Two grayanane diterpenoids, crotonkinensins A (328) and B (329) from the leaves of C. tonkinensis, were reported to decrease the LPS-induced COX-2 promoter activity in Raw 264.7 cells with IC50 values of 7.14 ± 0.2 and 5.49 ± 0.2 μM, respectively [100]. Two benzoate derivatives (379, 380) were obtained from C. hutchinsonianus. Compound 379 showed significant activity against COX-1 (IC50, 4.95 ± 0.58 μg/mL) and COX-2 (IC50, 2.11 ± 1.3 μg/mL), while compound 380 (IC50, 1.88 ± 0.17 μg/mL) preferentially inhibited COX-2 [119].

3.3. Antifungal Activity

Two benzoate derivatives (379380) were isolated from C. hutchinsonianus, and exhibited antifungal activity against Candida albicans (IC50, 11.41 ± 1.44, and 5.36 ± 0.01 μg/mL, respectively) [119]. Ursane triterpenoid (348) from the root of C. bonplandianum, displayed the antifungal activity against Calletotricheme camellie (IC50, 10 μg/mL), Fussarium equisitae (IC50, <15 μg/mL), Alterneria alternata (IC50, 10 μg/mL), Curvularia eragrostidies (IC50, <10 μg/mL) and Colletorichum gloeosporiodes (IC50, 15 μg/mL) [107].

3.4. Acetylcholinesterase Inhibitory Activity

An indole alkaloid derivative 376, isolated from the leaves of C. heliotropiifolius, exhibited the acetylcholinesterase inhibitory activity with IC50 values of 17.8 ± 0.6 μM [116]. Compund 378 from C. sylvaticus, also displayed the same activity [118].

3.5. Neurite Outgrowth-Promoting Activity

Two clerodane diterpenoids, crotonpenes A (36) and B (37) were isolated from C. yanhuii, which markedly increased the NGF (20 ng/mL)-induced proportion of neurite bearing cells by 59%, and 47% at 15 μM, respectively [23]. Crotoeurins A–C (40–42) obtained from C. euryphyllus, were found to display neurite outgrowth-promoting activity on NGF mediated PC12 cells at concentration of 10 μM. The percentages of neurite-bearing cells were 9.72%, 14.90%, and 7.14%, respectively [25].

3.6. Other Activities

Besides the above activities, other biological activities have also been reported. Crotonolide G (32), from the aerial parts of C. laui, was found to exhibit potent antibacterial activity (MIC, 43.4 μM) against four strains of Gram-positive bacteria, namely, Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, and Bacillus subtilis [21]. Crassifolin H (39) was obtained from roots of C. crassifolius as an angiogenic inhibitor by reducing vessel formation to 59.3% at 15 μg/mL [34]. Tigliane diterpene (111) was isolated from the leaves of C. mauritianus, which inhibited chikungunya virus-induced cell death in cell culture with EC50s of 4.0 ± 0.8 μM [43]. The leaves of C. tiglium yielded two tigliane diterpenoids (135, 136), which displayed significant antitubercular activities with MIC values of 19.5, and 20.9 μM, respectively [51]. Compounds (162165) were four ent-kaurane diterpenes from C. tonkinensis, which significantly stimulated differentiation in osteoblasts [64]. From the twigs and leaves of C. cascarilloides, two crotofolane diterpenoid alkaloids cascarinoids B–C (226, 227) were obtained, both of which displayed moderate activities against the ConA-induced proliferation of T lymphocyte cells and/or LPS-induced proliferation of B lymphocyte cells with IC50 values ranging from 6.14 to 16.27 μM [71]. Meroditerpenoid (336), from C. steenkampianus, showed antiplasmodial activities of 15.8 (D10), 9.1 (W2), and 9.4 (Dd2) μM [102]. Indole alkaloid (377) was found in C. mauritianus with antioxidant activity (IC50, 30.0.0 ± 0.7 μM) by the DPPH radical scavenging assay [117]. Bioactivity-guided fractionation of the root bark of C. jatrophoides resulted in the isolation of musidunin (388) and musiduol (389), both of which showed insect antifeedant activities (PC50, 3 μg/mL, PC95, 10 μg/mL; PC50, 4 μg/mL, PC95, 20 μg/mL, respectively) against the second-instar larvae of Pectinophora gossypiella in a leaf disk assay [126].

4. Conclusions

In the present review, we systematically summarized the chemical constituents and biological activity studies of Croton species covering from 2006 to 2018. To date, a total of 399 new compounds were reported from Croton species, which included 339 diterpenoids, seven sesquiterpenoids, 21 glycosides, eight alkaloids, and 24 miscellaneous compounds (Figure 14). Obviously, diterpenoids are characteristic components for Croton species. The diterpenoids with clerodane, tigliane, kaurane, crotofolane, labdane, and cembrane skeletons are among the most studied diterpenoids isolated from Croton species (Figure 14). Although the current studies have shown that these isolated compounds from Croton species possessed diversified biological activities, many compounds have never been biologically tested. Moreover, most studies conducted so far have focused mainly on in vitro cytotoxic assays. Further studies on the mechanism of actions and the structure activity relationship are needed in order to provide a better understanding of the chemical constituents from Croton species as potential medicines. Increasing interest in the chemistry and pharmaceutics of Croton species may promote new progress in finding and developing novel compounds.

Author Contributions

W.-H.X. classified the chemical constituents and drafted the structural formulas, wrote the manuscript; W-Y L. collected literatures; Q.L. managed references, overall responsibility.

Funding

We are thankful for financial supports from the Natural Science Foundation of China (NSFC) (21362035); The Initial Foundation of Scientific Research for the introduction of talents from Southwest Forestry University for Wen-Hui Xu (20130916); and Opening Research Foundation from Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University (KLE201807).

Conflicts of Interest

The authors declare no conflict of interest.

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  • Sample Availability: Samples of the compounds are not available from the authors.
Figure 1. Clerodane type diterpenoids from the genus Croton.
Figure 1. Clerodane type diterpenoids from the genus Croton.
Molecules 23 02333 g001aMolecules 23 02333 g001bMolecules 23 02333 g001c
Figure 2. Tigliane type diterpenoids from the genus Croton.
Figure 2. Tigliane type diterpenoids from the genus Croton.
Molecules 23 02333 g002aMolecules 23 02333 g002b
Figure 3. Kaurane type diterpenoids from the genus Croton 1.
Figure 3. Kaurane type diterpenoids from the genus Croton 1.
Molecules 23 02333 g003
Figure 4. Crotofolane type diterpenoids from the genus Croton.
Figure 4. Crotofolane type diterpenoids from the genus Croton.
Molecules 23 02333 g004
Figure 5. Labdane type diterpenoids from the genus Croton.
Figure 5. Labdane type diterpenoids from the genus Croton.
Molecules 23 02333 g005
Figure 6. Cembrane type diterpenoids from the genus Croton.
Figure 6. Cembrane type diterpenoids from the genus Croton.
Molecules 23 02333 g006
Figure 7. Abietane type diterpenoids from the genus Croton.
Figure 7. Abietane type diterpenoids from the genus Croton.
Molecules 23 02333 g007
Figure 8. Casbane, Halimane, Pimarane and Cleistanthane type diterpenoids from the genus Croton.
Figure 8. Casbane, Halimane, Pimarane and Cleistanthane type diterpenoids from the genus Croton.
Molecules 23 02333 g008
Figure 9. Grayanane, Atisane, Phytane, Laevinane type diterpenoids and Meroditerpenoids from the genus Croton.
Figure 9. Grayanane, Atisane, Phytane, Laevinane type diterpenoids and Meroditerpenoids from the genus Croton.
Molecules 23 02333 g009
Figure 10. Sesquiterpenoids, Sesterterpenoid and Triterpenoid from the genus Croton.
Figure 10. Sesquiterpenoids, Sesterterpenoid and Triterpenoid from the genus Croton.
Molecules 23 02333 g010
Figure 11. Glycosides from the genus Croton.
Figure 11. Glycosides from the genus Croton.
Molecules 23 02333 g011
Figure 12. Alkaloids from the genus Croton.
Figure 12. Alkaloids from the genus Croton.
Molecules 23 02333 g012
Figure 13. Miscellaneous compounds from the genus Croton.
Figure 13. Miscellaneous compounds from the genus Croton.
Molecules 23 02333 g013
Figure 14. The percentage of each type of compounds (left), the percentage of each type of diterpenoids (right) from Croton Species.
Figure 14. The percentage of each type of compounds (left), the percentage of each type of diterpenoids (right) from Croton Species.
Molecules 23 02333 g014
Table 1. Clerodane type diterpenoids from the genus Croton.
Table 1. Clerodane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
1ent-3,13E-clerodadiene-15-formateC21H34O2C. sylvaticus[12]
29-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic acidC20H28O4C. crassifolius[14]
39-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic esterC21H30O4C. crassifolius[14]
4Centrafricine IC21H24O6C. mayumbensis[19]
5MarrubiageninC20H28O4C. glabellus[15]
6Methyl 15,16-epoxy-3,13(16),14-ent-clerodatrien-18,19-olide-17-carboxylateC21H26O5C. oblongifolius[29]
7Dimethyl 15,16-epoxy-12-oxo-3,13(16),14-ent-clerodatriene-17,18-dicarboxylateC22H28O6C. oblongifolius[29]
8IsoteucvinC19H20O5C. jatrophoides[30]
9JatrophoidinC21H22O7C. jatrophoides[30]
108-EpicordatinC21H26O6C. palanostigma[31]
11laevigatbenzoateC27H31O5C. laevigatus[13]
123,4,15,16-diepoxy-cleroda-13(16),14-diene-12,17-olideC20H26O4C. oblongifolius[22]
13Crassifolin AC21H30O4C. crassifolius[16]
14Crassifolin BC20H29O4C. crassifolius[16]
15Crassifolin CC21H24O5C. crassifolius[16]
16Crassifolin DC21H24O6C. crassifolius[16]
17Crassifolin EC20H23O6C. crassifolius[16]
18Crassifolin FC23H29O7C. crassifolius[16]
19Crassifolin GC19H20O6C. crassifolius[16]
20Methyl 3-oxo-12-epibarbascoateC21H26O6C. urucurana[32]
21Laevinoids AC20H22O5C. laevigatus[20]
22Laevinoids BC20H23O5ClC. laevigatus[20]
23Crotonolide AC20H18O6C. laui[21]
24Crotonolide BC21H24O6C. laui[21]
25Isocrotonolide BC21H24O6C. laui[21]
26Crotonolide CC23H26O8C. laui[21]
27Isocrotonolide CC23H26O8C. laui[21]
28Crotonolide DC21H26O6C. laui[21]
29Isocrotonolide DC21H26O6C. laui[21]
30Crotonolide EC20H26O4C. laui[21]
31Crotonolide FC20H26O4C. laui[21]
32Crotonolide GC20H32OC. laui[21]
33Crotonolide HC20H32O4C. laui[21]
3412-Deoxycrotonolide HC20H32O3C. laui[21]
35CrotonoligaketoneC23H26O8C. oligandrum[33]
36Crotonpene AC20H26O3C. yanhuii[23]
37Crotonpene BC21H28O5C. yanhuii[23]
38Crassifolin IC20H22O6C. crassifolius[34]
39Crassifolin HC19H20O5C. crassifolius[34]
40Crotoeurin AC38H36O1C. euryphyllus[25]
41Crotoeurin BC20H24O6C. euryphyllus[25]
42Crotoeurin CC20H22O6C. euryphyllus[25]
433-Oxo-15,16-epoxy-4α,12-dihydroxy-ent-neo-clerodan-13(16),14-dieneC20H30O4C. limae[35]
4415,16-Epoxy-3α,4α,12-trihydroxy-ent-neo-clerodan- 13(16),14-dieneC20H32O4C. limae[35]
453α,4α,15,16-Tetrahydroxy-ent-neo-cleroda-13E-eneC20H36O4C. limae[35]
46Cracroson AC19H21O6C. crassifolius[26]
47Cracroson BC20H22O6C. crassifolius[26]
48Cracroson CC19H19O4NC. crassifolius[26]
49Crassifolin JC20H20O5C. crassifolius[36]
60Crotocorylifuran-2-oneC22H24O8C.megalocarpoides[27]
61Megalocarpoidolide DC22H22O8C.megalocarpoides[27]
627,8-DehydrocrotocorylifuranC22H24O7C.megalocarpoides[27]
63Megalocarpoidolide EC22H24O8C.megalocarpoides[27]
64Megalocarpoidolide FC22H24O8C.megalocarpoides[27]
65Megalocarpoidolide GC22H24O9C.megalocarpoides[27]
66Megalocarpoidolide HC24H28O10C.megalocarpoides[27]
67Launine KC27H36O3C. laui[37]
68Crassin AC17H20O4C. crassifolius[17]
69Crassin BC17H20O4C. crassifolius[17]
70Crassin CC21H24O6C. crassifolius[17]
71Crassin DC20H20O5C. crassifolius[17]
72Crassin EC19H20O3C. crassifolius[17]
73Crassin FC19H18O7C. crassifolius[17]
74Crassin GC20H26O5C. crassifolius[17]
75Crassin HC21H30O5C. crassifolius[17]
76Crassifolius AC20H22O5C. crassifolius[38]
77Crassifolius BC21H24O6C. crassifolius[38]
78Crassifolius CC21H26O5C. crassifolius[38]
79Crolaevinoid CC27H28O6C. laevigatus[39]
80Crolaevinoid DC27H32O8C. laevigatus[39]
81Crolaevinoid EC20H28O6C. laevigatus[39]
82Crolaevinoid FC21H30O5C. laevigatus[39]
83NorcrassifolinC19H18O4C. crassifolius[28]
84Hypolein AC20H26O4C. hypoleucus[24]
85Hypolein BC20H28O3C. hypoleucus[24]
86Hypolein CC20H28O3C. hypoleucus[24]
87Cracroson EC19H20O6C. crassifolius[40]
88Cracroson FC19H20O6C. crassifolius[40]
89Cracroson GC21H26O7C. crassifolius[40]
9012-Epi-megalocarpoidolide DC22H22O8C. oligandrus[18]
91Crotonolins AC22H22O10C. oligandrus[18]
92Crotonolins BC22H22O10C. oligandrus[18]
Table 2. Tigliane type diterpenoids from the genus Croton.
Table 2. Tigliane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
9312-O-isobutyrylphorbol-13-decanoateC34H52O8C. tiglium[45]
9412-O-(2-methyl)butyrylphorbol-13-octanoateC33H50O8C. tiglium[45]
9512-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetateC29H43NO7C. ciliatoglandulifer[41]
9612-O-[(2S)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetateC29H43NO7C. ciliatoglandulifer[41]
9712-O-[(2R)-N,N-Dimethyl-3-methylbutanoyl]phorbol 13-acetateC29H43NO8C. ciliatoglandulifer[41]
9812-O-[3-Methyl-2-butenoyl]-4-deoxyphorbol 13-acetateC27H36NO7C. ciliatoglandulifer[41]
9912-O-(2-methyl)butyrylphorbol-13-tiglateC30H42O8C. tiglium[46]
10012-O-tiglylphorbol-13-propionateC28H38O8C. tiglium[46]
10113-O-acetylphorbol-20-oleateC40H62O8C. tiglium[46]
10612-O-tiglyl-4-deoxy-4α-phorbol-13-(2-methyl)butyrateC30H42O7C. tiglium[46]
107AlienusolinC42H66O8C. alienus[42]
10812-O-acetyl-5,6-didehydro-7-oxophorbol-13-yl 2-methylbutanoateC27H36O9C. tiglium[47]
10912-O-acetyl-5,6-didehydro-7-oxophorbol-13-yl2-methylpropanoateC26H34O9C. tiglium[47]
11012-Oacetyl-5,6-didehydro-6,7-dihydro-7-hydroxyphorbol-13-yl 2-methylbutanoateC27H38O9C. tiglium[47]
11112-O-decanoyl-7-hydroperoxy-phorbol-5-ene-13-acetateC32H42O10C. mauritianus[43]
11220-deoxy-20-oxophorbol12-tiglate 13-(2-methyl)butyrateC30H40O8C. tiglium[48]
11312-O-acetylphorbol-13-isobutyrateC26H36O8C. tiglium[48]
11412-O-benzoylphorbol-13-(2-methyl)butyrateC32H40O8C. tiglium[48]
11512-O-tiglyl-7-oxo-5-ene-phorbol-13-(2-methyl)butyrateC30H40O9C. tiglium[48]
11613-O-(2-metyl)butyryl-4-deoxy-4a-phorbolC25H36O6C. tiglium[48]
117Crotignoid AC30H42O10C. tiglium[49]
118Crotignoid BC29H40O10C. tiglium[49]
119Crotignoid CC30H42O9C. tiglium[49]
120Crotignoid DC29H40O9C. tiglium[49]
121Crotignoid EC29H38O9C. tiglium[49]
122Crotignoid FC28H36O9C. tiglium[49]
123Crotignoid GC30H44O8C. tiglium[49]
124Crotignoid HC29H38O8C. tiglium[49]
125Crotignoid IC30H44O8C. tiglium[49]
126Crotignoid JC31H38O8C. tiglium[49]
127Crotignoid KC29H34O7C. tiglium[49]
128Crotusin AC36H54O10C. caudatus[44]
129Crotusin BC46H72O11C. caudatus[44]
130Crotusin CC36H52O11C. caudatus[44]
13112-O-tiglylphorbol-4-deoxy- 4β-phorbol-13-acetateC27H36O7C. tiglium[50]
13212-O-tiglylphorbol-4-deoxy-4β-phorbol-13-hexadecanoateC41H64O7C. tiglium[50]
13313-O-acetylphorbol-4-deoxy-4β-phorbol-20-oleateC40H62O7C. tiglium[50]
13413-O-acetylphorbol-4-deoxy-4β-phorbol-20-linoleateC40H60O7C. tiglium[50]
1354-deoxy-20-oxophorbol 12-tiglyl 13-acetateC27H34O7C. tiglium[51]
1367-oxo-5-ene-phorbol-13-(2-methylbutyrate)C25H34O8C. tiglium[51]
1377-hydroxyl-phorbol-5-ene-13-(2-methyl)butyrateC25H36O8C. tiglium[51]
Table 3. Kaurane type diterpenoids from the genus Croton.
Table 3. Kaurane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
149CaracasineC21H30O3C. caracasana[53]
150Caracasine acidC20H28O3C. caracasana[53]
151Kongensin AC22H30O5C. kongensis[56]
152Kongensin BC22H30O6C. kongensis[56]
153Kongensin CC20H28O5C. kongensis[56]
154Kongensin DC20H28O4C. kongensis[57]
155Kongensin EC26H36O7C. kongensis[57]
156Kongensin FC24H34O5C. kongensis[58]
157Crotonkinin AC20H30O2C. tonkinensis[62]
158Crotonkinin BC22H32O4C. tonkinensis[62]
15914-epi-hyalic acidC20H28O4C. argyrophylloides[63]
16014-[(2-methylbutanoyl)oxy]-3,4-seco-ent-kaura-4(19),16-dien-3-oic acidC25H39O4C. megistocarpus[54]
16114-{[(2Z)-2-methylbut-2-enoyl]oxy}-3,4-seco-ent-kaura-4(19),16-dien-3-oic acidC25H37O4C. megistocarpus[54]
162ent-11β-acetoxykaur-16-en-18-olC22H34O3C. tonkinensis[64]
163ent-11α-hydroxy-18-acetoxykaur-16-eneC22H34O3C. tonkinensis[64]
164ent-14β-hydroxy-18-acetoxykaur-16-eneC22H34O3C. tonkinensis[64]
165ent-7α-hydroxy-18-acetoxykaur-16-eneC22H34O3C. tonkinensis[64]
166ent-14S*-hydroxykaur-16-en-19-oic acidC20H30O3C. pseudopulchellus[65]
167ent-14S*,17-dihydroxykaur-15-en-19-oic acidC20H30O4C. pseudopulchellus[65]
168ent-3,4-seco-17-oxo-kaur-4(19),15(16)-dien-3-oic acidC20H28O3C. oblongifolius[55]
169Crotonkinin CC22H30O5C. tonkinensis[66]
170Crotonkinin DC24H34O6C. tonkinensis[66]
171Crotonkinin EC24H34O5C. tonkinensis[66]
172Crotonkinin FC24H34O5C. tonkinensis[66]
173Crotonkinin GC23H36O5C. tonkinensis[66]
174Crotonkinin HC22H36O4C. tonkinensis[66]
175Crotonkinin IC24H36O5C. tonkinensis[66]
176Crotonkinin JC23H34O5C. tonkinensis[66]
17714β-hydroxy-3-oxo-ent-kaur-16-eneC20H30O2C. kongensis[67]
178Kongeniod AC21H30O3C. kongensis[59]
179Kongeniod BC21H30O4C. kongensis[59]
180Kongeniod CC23H32O5C. kongensis[59]
18115-oxo-17(10′-α-pinenyl)-kauran-18-oic acidC30H44O3C. limae[35]
182Micansinoic acidC40H58O7C. micans[60]
183Isomicansinoic acidC40H58O7C. micans[60]
184Dimethylester of micansinoicC42H62O7C. micans[60]
185Methyl-micansinoic acidC41H60O7C. micans[60]
186Ethyl-micansinoic acidC42H62O7C. micans[60]
187Crotonkinensin CC40H62O8C. tonkinensis[61]
188Crotonkinensin DC44H66O10C. tonkinensis[61]
Table 4. Crotofolane type diterpenoids from the genus Croton.
Table 4. Crotofolane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
189Crotocascarin AC25H32O7C. cascarilloides[68]
190Crotocascarin BC25H32O7C. cascarilloides[68]
191Crotocascarin CC25H32O8C. cascarilloides[68]
192Crotocascarin DC25H32O6C. cascarilloides[68]
193Crotocascarin EC26H34O8C. cascarilloides[68]
194Crotocascarin FC24H30O7C. cascarilloides[68]
195Crotocascarin GC24H30O7C. cascarilloides[68]
196Crotocascarin HC24H30O8C. cascarilloides[68]
197Crotocascarin αC24H32O8C. cascarilloides[68]
198Crotocascarin βC24H32O7C. cascarilloides[68]
199(5β,6β)-5,6: 13,16-diepoxycrotofola-4(9),10(18),13,15-tetraen-1-oneC20H22O3C. argyrophyllus[72]
200(5β,6β)-5,6: 13,16-diepoxy-2-epicrotofola-4(9),10(18),13,15-tetraen-1-oneC20H22O3C. argyrophyllus[72]
201(5β,6β)-5,6: 13,16-diepoxy-16-hydroxycrotofola-4(9),10(18),13,15-tetraen-1-oneC20H22O4C. argyrophyllus[72]
202(5β,6β)-5,6: 13,16-diepoxy-16-hydroxy-2-epi-crotofola-4(9),10(18),13,15-tetraen-1-oneC20H22O4C. argyrophyllus[72]
203Crotocarasin AC20H22O4C. caracasanus[73]
204Crotocarasin BC20H22O4C. caracasanus[73]
205Crotocarasin CC22H26O5C. caracasanus[73]
206Crotocarasin DC22H26O5C. caracasanus[73]
207EBC-162C20H24O2C. insularis[74]
208EBC-233C20H24O4C. insularis[74]
209EBC-300C20H24O4C. insularis[74]
210EBC-240C20H26O5C. insularis[74]
211EBC-241C20H26O5C. insularis[74]
212Crotocascarin IC20H24O5C. cascarilloides[69]
213Crotocascarin JC20H24O6C. cascarilloides[69]
214Crotocascarin KC20H24O5C. cascarilloides[69]
215Crotocascarin γC19H24O6C. cascarilloides[69]
216Crotocascarin LC22H26O7C. cascarilloides[70]
217Crotocascarin MC21H26O6C. cascarilloides[70]
218Crotocascarin NC20H22O6C. cascarilloides[70]
219Crotocascarin OC25H34O9C. cascarilloides[70]
220Crotocascarin PC25H34O8C. cascarilloides[70]
221Crotocascarin QC25H32O7C. cascarilloides[70]
222NeocrotocascarinC25H32O8C. cascarilloides[70]
223Crotodichogamoin AC20H22O4C. dichogamus[75]
224Crotodichogamoin BC20H22O2C. dichogamus[75]
225Cascarinoid AC28H31NO5C. cascarilloides[71]
226Cascarinoid BC28H31NO5C. cascarilloides[71]
227Cascarinoid CC28H31NO6C. cascarilloides[71]
Table 5. Labdane type diterpenoids from the genus Croton.
Table 5. Labdane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
228Labdinine NC20H34O3C. laui[76]
229ent-12,15-dioxo-3,4-seco-4,8,13-labdatrien-3-oic acidC20H28O4C. stipuliformis[78]
230ent-12,15-epoxy-3,4-seco-4,8,12,14-labdatetraen-3-oic acidC20H28O3C. stipuliformis[78]
231ent-15-nor-14-oxo-3,4-seco-4,8,12(E)-labdatrien-3-oic acidC19H28O3C. stipuliformis[78]
232ent-12,15-dioxo-8,13-labdadien-3a-olC20H28O3C. stipuliformis[78]
233Crotonlaevin AC18H30O4C. laevigatus[79]
234Crotonlaevin BC20H32O5C. laevigatus[79]
235Crotonlaevin CC21H34O5C. laevigatus[79]
236Crotonlaevin DC18H30O3C. laevigatus[79]
237Crotonlaevin EC20H32O5C. laevigatus[79]
238Crotonlaevin FC22H34O6C. laevigatus[79]
239Crotonlaevin GC22H36O5C. laevigatus[79]
240Crotonlaevin HC22H36O5C. laevigatus[79]
241Crotonlaevin IC20H34O4C. laevigatus[79]
242Crotonlaevin JC20H30O3C. laevigatus[79]
243Crotonlaevin KC20H28O3C. laevigatus[79]
244Crotonlaevin LC20H30O4C. laevigatus[79]
245Crotonlaevin MC20H30O4C. laevigatus[79]
246Crotonlaevin NC20H30O3C. laevigatus[79]
247Crotonlaevin OC20H30O3C. laevigatus[79]
248Crotonlaevin PC20H30O3C. laevigatus[79]
249Crotonolide IC20H34O3C. laui[21]
250Crotonolide JC19H30O3C. laui[21]
251Launine AC19H32O3C. laui[82]
252Launine BC19H32O4C. laui[82]
253Launine CC20H34O3C. laui[82]
254Launine DC20H34O3C. laui[82]
255Launine EC20H32O5C. laui[82]
256Launine FC20H32O5C. laui[82]
257Launine GC20H30O4C. laui[82]
258Launine HC20H30O4C. laui[82]
259Launine IC20H34O3C. laui[82]
26015,16-epoxy-4-hydroxy-labda-13(16),14-dien-3,12-dioneC20H28O4C. jacobinensis[77]
261Crotondecalvatin AC29H42O4C. decalvatus[80]
262Crotondecalvatin BC30H42O6C. decalvatus[80]
263Bicrotonol AC40H68O4C. crassifolius[81]
Table 6. Cembrane type diterpenoids from the genus Croton.
Table 6. Cembrane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
264Launine OC20H34O2C. laui[76]
265Launine PC21H36O2C. laui[76]
266Furanocembranoid 1C20H30O2C. oblongifolius[83]
267Furanocembranoid 2C20H30O3C. oblongifolius[83]
268Furanocembranoid 3C20H32O4C. oblongifolius[83]
269Furanocembranoid 4C20H32O5C. oblongifolius[83]
270Laevigatlactone AC20H30O3C. laeVigatus[84]
271Laevigatlactone CC20H30O3C. laeVigatus[84]
272Laevigatlactone BC20H30O3C. laeVigatus[84]
273Laevigatlactone DC20H30O3C. laeVigatus[84]
274Laevigatlactone EC20H30O4C. laeVigatus[84]
275Laevigatlactone FC20H30O5C. laeVigatus[84]
276(+)-[1R*,2S*,7S*,8S*,12R*]-7,8-Epoxy-2,12-cyclocembra-3E,10Zdien-20,10-olideC20H28O3C. gratissimus[85]
277(+)-[1R*,10R*]-Cembra-2E,4E,7E,11Z-tetraen-20,10-olideC20H28O2C. gratissimus[85]
278(+)-[1R*,4S*,10R*]-4-Hydroxycembra-2E,7E,11Z-trien-20,10-olideC20H30O3C. gratissimus[85]
279(−)-[1R*,4R*,10R*]-4-Hydroxycembra-2E,7E,11Z-trien-20,10-olideC20H30O3C. gratissimus[85]
280(−)-(1R*,4R*,10R*)-4-Methoxycembra-2E,7E,11Z-trien-20,10-olideC21H32O3C. gratissimus[86]
281(−)-(1S*,4R*,10R*)-1-Hydroxy-4-methoxycembra-2E,7E,11Ztrien-20,10-olideC21H32O4C. gratissimus[86]
282(−)-(1S*,4S*,10R*)-1,4-Dihydroxycembra-2E,7E,11Z-trien-20,10-olideC20H30O4C. gratissimus[86]
283(−)-(1S*,4S*,10R*)-1,4-Dihydroxycembra-2E,7E,11Z-trien-20,10-olideC20H30O4C. gratissimus[86]
284(+)-(10R*)-Cembra-1E,3E,7E,11Z,16-pentaen-20,10-olideC20H26OC. gratissimus[86]
285(+)-(10R*)-Cembra-1Z,3Z,7E,11Z,15-pentaen-20,10-olideC20H26OC. gratissimus[86]
286(+)-(5R*,10R*)-5-Methoxycembra-1E,3E,7E,11Z,15-pentaen-20,10-olideC21H30O3C. gratissimus[86]
287(+)-(1S*,4S*,7R*,10R*)-1,4,7-Trihydroxycembra-2E,8(19),11Z-trien-20,10-olideC20H30O5C. gratissimus[86]
288(−)-(1S*,4S*,7S*,10R*)-1,4,7-Trihydroxycembra-2E,8(19),11Z-trien-20,10-olideC20H30O3C. gratissimus[86]
289(+)-(1S*,4R*,8S*,10R*)-1,4,8-Trihydroxycembra-2E,6E,11Z-trien-20,10-olideC20H30O5C. gratissimus[86]
290Cembranoid 1C20H30O4C. longissimus[87]
291Cembranoid 2C20H30O3C. longissimus[87]
281(−)-(1S*,4R*,10R*)-1-Hydroxy-4-methoxycembra-2E,7E,11Ztrien-20,10-olideC21H32O4C. gratissimus[86]
282(−)-(1S*,4S*,10R*)-1,4-Dihydroxycembra-2E,7E,11Z-trien-20,10-olideC20H30O4C. gratissimus[86]
283(−)-(1S*,4S*,10R*)-1,4-Dihydroxycembra-2E,7E,11Z-trien-20,10-olideC20H30O4C. gratissimus[86]
284(+)-(10R*)-Cembra-1E,3E,7E,11Z,16-pentaen-20,10-olideC20H26OC. gratissimus[86]
285(+)-(10R*)-Cembra-1Z,3Z,7E,11Z,15-pentaen-20,10-olideC20H26OC. gratissimus[86]
286(+)-(5R*,10R*)-5-Methoxycembra-1E,3E,7E,11Z,15-pentaen-20,10-olideC21H30O3C. gratissimus[86]
287(+)-(1S*,4S*,7R*,10R*)-1,4,7-Trihydroxycembra-2E,8(19),11Z-trien-20,10-olideC20H30O5C. gratissimus[86]
288(−)-(1S*,4S*,7S*,10R*)-1,4,7-Trihydroxycembra-2E,8(19),11Z-trien-20,10-olideC20H30O3C. gratissimus[86]
289(+)-(1S*,4R*,8S*,10R*)-1,4,8-Trihydroxycembra-2E,6E,11Z-trien-20,10-olideC20H30O5C. gratissimus[86]
290Cembranoid 1C20H30O4C. longissimus[87]
291Cembranoid 2C20H30O3C. longissimus[87]
Table 7. Abietane type diterpenoids from the genus Croton.
Table 7. Abietane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
292Isolophanthin EC20H30O3C. megalocarpoides[27]
293rel-(1R,4aR,5R,8R)-methyl-7-(1-(methoxycarbonyl)vinyl)-5,8-diacetoxy-1,2,3,4a,5,6,7,8,9,10,10a-dodecahydro-1,4a-dimethyl-2-oxophenanthrene-1-carboxylateC26H34O9C. argyrophylloides[63]
294Crotontomentosin AC20H26O2C. caudatus[88]
295Crotontomentosin BC20H30O3C. caudatus[88]
296Crotontomentosin DC20H24O2C. caudatus[88]
297Crotontomentosin CC20H28O2C. caudatus[88]
298Crotontomentosin EC22H32O3C. caudatus[88]
299Crotolaevigatone AC20H24O3C. laevigatus[89]
300Crotolaevigatone BC20H26O2C. laevigatus[89]
301Crotolaevigatone CC20H26O3C. laevigatus[89]
302Crotolaevigatone DC20H28O4C. laevigatus[89]
303Crotolaevigatone EC19H24O2C. laevigatus[89]
304Crotolaevigatone FC20H30O4C. laevigatus[89]
305Crotolaevigatone GC20H30O4C. laevigatus[89]
Table 8. Casbane type diterpenoids from the genus Croton.
Table 8. Casbane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
3061,4-dihydroxy-2E,6E,12E-trien-5-one-casbaneC20H30O3C.nepetaefolius[90]
3074-hydroxy-2E,6E,12E-5-one-casbaneC20H29O3C.nepetaefolius[90]
3081-hydroxy-(2E,6Z,12E)-casba-2,6,12-triene-4,5-dioneC20H28O3C.argyrophyllus[91]
3096E,12E-casba-1,3,6,12-tetraen-1,4-epoxy-5-oneC20H26O2C.argyrophyllus[91]
310(2E,5β,6E,12E)-5-hydroxycasba-2,6,12-trien-4-oneC20H30O2C. argyrophyllus[72]
311EBC-324C20H28O5C. insularis[92]
312EBC-329C20H26O4C. insularis[92]
Table 9. Halimane type diterpenoids from the genus Croton.
Table 9. Halimane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
313Crassifoliusin AC21H24O5C.crassifolius[95]
314Crotontomentosin FC21H30O3C.caudatus[88]
315Crolaevinoid AC27H30O7C.laevigatus[39]
316Crolaevinoid BC20H26O4C.laevigatus[39]
317Crothalimene AC20H26O4C.dichogamus[75]
318Crothalimene BC20H30O2C.dichogamus[75]
Table 10. Pimarane type diterpenoids from the genus Croton.
Table 10. Pimarane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
319ent-3β-hydroxypimara-8(14),9,15-trien-12-oneC20H28O2C.insularis[98]
320EBC-316C20H26O2C.insularis[99]
321EBC-325C20H26O4C.insularis[99]
322EBC-326C20H26O4C.insularis[99]
323EBC-327C20H24O3C.insularis[99]
324EBC-345C20H30O4C.insularis[99]
Table 11. Cleistanthane type diterpenoids from the genus Croton.
Table 11. Cleistanthane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
3253-hydroxycleistantha-13(17),15-dieneC20H32OC.oblongifolius[93]
3263,4-seco-cleistantha-4(18),13(17),15-trien-3-oic acidC20H30O2C.oblongifolius[93]
327rel-(5β,8α,10α)-8-hydroxy-13-methylpodocarpa-9(11),13-diene-3,12-dioneC18H25O3C.regelianus[94]
Table 12. Grayanane type diterpenoids from the genus Croton.
Table 12. Grayanane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
328Crotonkinensin AC20H24O4C.tonkinensis[100]
329Crotonkinensin BC20H26O3C.tonkinensis[100]
Table 13. Atisane type diterpenoids from the genus Croton.
Table 13. Atisane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
330CrotobarinC22H28O5C.barorum[101]
331CrotogoudinC20H26O3C.goudotii[101]
Table 14. Phytane type diterpenoids from the genus Croton.
Table 14. Phytane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
332Launine LC20H32O3C.laui[37]
333Launine MC20H32O2C.laui[37]
Table 15. Laevinane type diterpenoids from the genus Croton.
Table 15. Laevinane type diterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
334Crolaevinoid GC20H24O6C.laevigatus[39]
335Crolaevinoid HC21H26O6C.laevigatus[39]
Table 16. Meroditerpenoids from the genus Croton.
Table 16. Meroditerpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
336Steenkrotin AC20H24O6C.steenkampianus[102]
337Steenkrotin BC20H28O7C.steenkampianus[102]
338Norcrassin AC17H22O7C.crassifolius[81]
339Cracroson DC21H26O6C.crassifolius[40]
Table 17. Sesquiterpenoids from the genus Croton.
Table 17. Sesquiterpenoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
3406α -methoxy-cypereneC16H26OC.muscicarpa[103]
341rel-(1R,4S,6R,7S,8αR)-decahydro-1-(hydroxymethyl)-4,9,9-trimethyl-4,7-(epoxymethano)azulen-6-olC15H26O3C. regelianus[94]
342Blumenol AC13H20O3C. pedicellatus[104]
343Crocrassins AC15H24O3C. crassifolius[105]
344Crocrassins BC16H26O3C. crassifolius[105]
3451,3,5-cadinatriene-(7R,10S)-diolC15H25O2C. dichogamus[75]
346Cracroson HC15H22O3C. crassifolius[40]
Table 18. Sesterterpenoid from the genus Croton.
Table 18. Sesterterpenoid from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
347PseudopulchellolC25H40OC.pseudopulchellus[106]
Table 19. Triterpenoid from the genus Croton.
Table 19. Triterpenoid from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
3483α-hydroxy-urs-12,15-dienC30H48OC.bonplandianum[107]
Table 20. Glycosides from the genus Croton.
Table 20. Glycosides from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
349Cyperenoic acid-9-O-β-d-glucopyranosideC21H32O8C. crassifolius[108]
3503-O-β-d-xylopyranosylspathodic acidC35H56O9C. lachnocarpus[109]
351Helichrysoside-3-methyletherC31H28O14C. zambesicus[110]
352Crotonionoside AC29H42O11C. cascarilloides[111]
353Crotonionoside BC30H44O12C. cascarilloides[111]
354Crotonionoside CC24H42O12C. cascarilloides[111]
355Crotonionoside DC31H46O14C. cascarilloides[111]
356Crotonionoside EC35H52O16C. cascarilloides[111]
357Crotonionoside FC24H42O11C. cascarilloides[111]
358Crotonionoside GC29H40O11C. cascarilloides[111]
359Oblongionoside AC24H42O12C. oblongifolius[112]
360Oblongionoside BC24H42O12C. oblongifolius[112]
361Oblongionoside CC24H44O11C. oblongifolius[112]
362Oblongionoside DC24H44O11C. oblongifolius[112]
363Oblongionoside EC19H36O8C. oblongifolius[112]
364Oblongionoside FC19H36O8C. oblongifolius[112]
365Blumenol A glucosideC19H30O8C. pedicellatus[10]
366SparsiosideC53H102O10C. sparsiorus[113]
3673,12-dioxo-15,16-epoxy-4α-hydroxy-6-(β-glucopyranosyl)-ent-neo-clerodan-13(16),14-dieneC26H38O10C. limae[35]
368Isocrotofolane glucosideC26H38O9C. cascarilloides[69]
3692-methoxyphenol-β-d-(6-O-β-d-apiofuranosyl) glucopyranosideC18H26O11C. cascarilloides[69]
Table 21. Alkaloids from the genus Croton.
Table 21. Alkaloids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
370Crotamide AC36H65NOC. sparsiflorus[114]
371Crotamide BC38H69NOC. sparsiflorus[114]
372CrotonineC12H14N2O4C. tiglium[97]
373Crotonimide AC16H20N2O3C. pullei[115]
374CrotsparsidineC17H17O3NC. sparsiflorus[96]
375Crotonimide C.C20H20N2O3C. alienus[42]
3766-Hydroxy-1-methyl-2-dimethyl-3,4-tetrahydro-b-carbo-lineC14H19N2OC. heliotropiifolius[116]
377N-trans-feruloyl-3,5-dihydroxyindolin-2-oneC20H20N2O6C. echioides[117]
Table 22. Benzoate derivatives from the genus Croton.
Table 22. Benzoate derivatives from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
3782′-(3′’,4′’-dihydroxyphenyl)-ethyl-4-hydroxybenzoateC15H14O5C.sylvaticus[118]
3793-(4-hydroxy-3,5-dimethoxyphenyl)-propyl benzoateC18H20O5C.hutchinsonianus[119]
3803-(4-hydroxyphenyl)-propyl benzoateC16H16O3C.hutchinsonianus[119]
Table 23. Pyran-2-one derivatives from the genus Croton.
Table 23. Pyran-2-one derivatives from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
381Crotonpyrone AC17H28O3C.crassifolius[120]
382Crotonpyrone BC17H26O3C.crassifolius[120]
383Crotonpyrone CC19H28O3C.crassifolius[121]
Table 24. Cyclicpeptides from the genus Croton.
Table 24. Cyclicpeptides from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
384CrotogossamideC37H56N10O11C.gossypifolius[122]
385[1−9-NαC]-crourorb A1C37H56N10O11C.urucurana[123]
Table 25. Tropone derivatives from the genus Croton.
Table 25. Tropone derivatives from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
386CrototroponeC10H12O4C.zehntneri[124]
387PernambuconeC15H18O2C.argyroglossum[125]
Table 26. Limonoids from the genus Croton.
Table 26. Limonoids from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
388MusiduninC31H38O11C.jatrophoides[126]
389MusiduolC30H38O10C.jatrophoides[126]
Table 27. Miscellaneous compounds from the genus Croton.
Table 27. Miscellaneous compounds from the genus Croton.
No.Compound NameMolecular FormulaSourcesRef
390CrotoncaudatinC22H22O9C.caudatus[127]
3918S-(−)-8-(4-hydroxy-3-methoxybenzoyl)-dihydrofuran-8(8′H)-oneC20H30O2C.kongensis[67]
392LobacerideC35H58O6C.lobatus[129]
393Laevifolin AC29H38O4C.laevifolius[128]
394Laevifolin BC29H38O4C.laevifolius[128]
3952,6-Dimethyl-1-oxo-4-indanecarboxylic acidC12H12O3C. steenkampianus[102]
3963(3′-Methoxy-5′-phenylfuran-2′-yl)propan-1-olC14H16O3C. oblongifolius[22]
397SparsifolC7H15O6C. sparsiflorus[96]
398SparsioamideC43H81NO5C. sparsiflorus[113]
399hexyl Z-ferulateC16H22O4C. laevigatus[89]
Table 28. Cytotoxic activity of compounds from the genus Croton.
Table 28. Cytotoxic activity of compounds from the genus Croton.
CompoundsTumor Cell LineActivity (IC50)Ref
Methyl 15,16-epoxy-3,13(16),14-ent-clerodatrien-18,19-olide-17-carboxylate (6)HuCCA-136.0 μg/mL[29]
KB26.0 μg/mL[29]
HeLa30.0 μg/mL[29]
MDA-MB23129.0 μg/mL[29]
T47D10.0 μg/mL[29]
Dimethyl-15,16-epoxy-12-oxo-3,13 (16)14-ent-clerodatriene-17,18-dicarboxylate (7)HuCCA-139.0 μg/mL[29]
KB27.0 μg/mL[29]
HeLa29.0 μg/mL[29]
MDA-MB23127.0 μg/mL[29]
T47D25.0 μg/mL[29]
Laevigatbenzoate (8)HeLa45.4 μM[13]
Crotonolide A (23)HL-609.42 μM[21]
P-3887.45 μM[21]
15-oxo-17(10′-α-pinenyl)-kauran-18-oic acid (181)HCT-1167.14 μg/mL[35]
OVCAR-88.19 μg/mL[35]
SF-295>10.0 μg/mL[35]
Launine K (67)HeLa14.5 μM[37]
MCF-762.5 μM[37]
Crassin H (75)HL-6011.8 ± 2.1 μM[17]
A5495.2 ± 0.4 μM[17]
Crassifolius A (76)Hep3B17.91 μM[38]
HepG242.04 μM[38]
Cracroson D (339)T2414.48 ± 0.65 μM[40]
A54925.64 ± 2.14 μM[40]
Cracroson E (87)T2422.99 ± 1.76 μM[40]
A54951.88 ± 14.07μM[40]
Hela3.9 μM[48]
DU1457.2 μM[48]
A5495.8 μM[48]
SGC-709113 μM[48]
H197510 μM[48]
HL6012 μM[48]
293T291.6 μM[48]
LX-2>500.0 μM[48]
12-O-benzoylphorbol-13-(2-methyl)butyrate (114)K56215 μM[48]
MOLT-412 μM[48]
U93717 μM[48]
MCF-720 μM[48]
Hela4.6 μM[48]
DU1454.3 μM[48]
A5496.9 μM[48]
SGC-709110 μM[48]
H19753.3 μM[48]
HL606.8 μM[48]
293T420.4 μM[48]
LX-2>500.0 μM[48]
12-O-tiglyl-7-oxo-5-ene-phorbol-13-(2-methyl)butyrate (115)K56217 μM[48]
MOLT-44.8 μM[48]
U93721 μM[48]
MCF-720 μM[48]
Hela5.0 μM[48]
DU14510 μM[48]
A54919 μM[48]
SGC-709123 μM[48]
H197510 μM[48]
HL6010 μM[48]
293T455.3 μM[48]
LX-2>500.0 μM[48]
13-O-(2-metyl)butyryl-4-deoxy-4a-phorbol (116)K5628.0 μM[48]
MOLT-49.9 μM[48]
U93718 μM[48]
MCF-724 μM[48]
H197510 μM[48]
HL6010 μM[48]
293T455.3 μM[48]
LX-2>500.0 μM[48]
Hela10 μM[48]
DU14510 μM[48]
A5494.5 μM[48]
SGC-70915.4 μM[48]
H19753.3 μM[48]
HL609.8 μM[48]
293T191.0 μM[48]
LX-2>500.0 μM[48]
Crotignoid A (117)HL-601.61 μM[49]
A5492.85 μM[49]
Crotignoid B (118)HL-6022.1 μM[49]
A54931.0 μM[49]
Crotignoid C (119)HL-6032.3 μM[49]
A5495.03 μM[49]
Crotignoid D (120)HL-6019.8 μM[49]
A54910.2 μM[49]
Crotignoid F (122)HL-6044.6 μM[49]
A5496.96 μM[49]
Crotignoid G (123)HL-6022.1 μM[49]
A5493.89 μM[49]
Crotignoid H (124)HL-609.97 μM[49]
A5498.08 μM[49]
Crotignoid I (125)HL-6014.8 μM[49]
A54924.4 μM[49]
Crotignoid J (126)HL-6014.2 μM[49]
A54929.5 μM[49]
Crotusin A (128)HL-6012.53 ± 0.37 μM[44]
SMMC-77217.06 ± 0.72 μM[44]
A5499.69 ± 0.41 μM[44]
MCF-79.56 ± 0.76 μM[44]
SW48014.88 ± 0.43 μM[44]
Crotusin B (129)HL-6019.39 ± 0.46 μM[44]
SMMC-772121.13 ± 0.29 μM[44]
A54914.66 ± 1.66 μM[44]
MCF-71.49 ± 0.23 μM[44]
SW48031.21 ± 3.20 μM[44]
Crotusin C (130)HL-604.19 ± 0.15 μM[44]
SMMC-77213.87 ± 0.12 μM[44]
A5492.44 ± 0.35 μM[44]
MCF-70.49 ± 0.04 μM[44]
SW4802.89 ± 0.01 μM[44]
12-O-tiglylphorbol-4-deoxy-4β-phorbol-13-acetate (131)SNU38759.5 ± 2.1 μM[50]
SNU39843.7 ± 1.5 μM[50]
12-O-tiglylphorbol-4-deoxy-4β-phorbol-13-hexadecanoate (132)SNU38730.2 ± 1.4 μM[50]
SNU39891.2 ± 3.7 μM[50]
13-O-acetylphorbol-4-deoxy-4β-phorbol-20-oleate (133)SNU3871.9 ± 0.2 μM[50]
SNU39813.5 ± 1.1 μM[50]
13-O-acetylphorbol-4-deoxy-4β-phorbol-20-linoleate (134)SNU3870.71 ± 0.08 μM[50]
SNU39818.2 ± 1.7 μM[50]
4-deoxy-20-oxophorbol 12-tiglyl 13-acetate (135)K5620.03 μM[51]
A5496.88 μM[51]
Huh-73.85 μM[51]
7-oxo-5-ene-phorbol-13-(2-methylbutyrate) (136)K5620.03 μM[51]
A5496.33 μM[51]
Huh-720.9 μM[51]
7-hydroxyl-phorbol-5-ene-13-(2-methyl)butyrate (137)K5620.07 μM[51]
A5498.86 μM[51]
Huh-711.6 μM[51]
13-O-(2-metyl)butyryl-phorbol (139)K5620.05 μM[51]
A54943.5 μM[51]
Huh-734.2 μM[51]
7-keto-12-O-tiglylphorbol-13-acetate (140)HL-606.22 ± 3.24 μg/mL[52]
A54918.0 ± 9.48 μg/mL[52]
Phorbol-13-isobutyrate (148)HL-600.22 ± 0.15 μg/mL[52]
14-epi-hyalic acid (159)HL-608.2 μM[63]
Kongeniod A (178)HL-601.27 ± 0.24 μM[59]]
A5495.74 ± 0.25 μM[59]
Kongeniod B (179)HL-600.47 ± 0.04 μM[59]
A5493.25 ± 0.91 μM[59]
Kongeniod C (180)HL-600.58 ± 0.17 μM[59]
Crotonkinensin D (188)MCF-79.4 ± 1.7 μM[61]
MCF-7/TAMR2.6 ± 0.9 μM[61]
MCF-7/ADR18.9 ± 0.6 μM[61]
MDA-MB-23122.0 ± 0.9 μM[61]
EBC-162 (207)HL-6015 μg/mL[74]
HT2915 μg/mL[74]
MCF-730 μg/mL[74]
MM9610 μg/mL[74]
NNF20 μg/mL[74]
K56250 μg/mL[74]
EBC-233 (208)HL-6010 μg/mL[74]
HT2980 μg/mL[74]
MCF-720 μg/mL[74]
MM966 μg/mL[74]
NNF50 μg/mL[74]
K56250 μg/mL[74]
EBC-300 (209)HL-6035 μg/mL[74]
HT29100 μg/mL[74]
MCF-7100 μg/mL[74]
MM9680 μg/mL[74]
NNF80 μg/mL[74]
K562100 μg/mL[74]
EBC-240 (210)HL-6045 μg/mL[74]
HT2980 μg/mL[74]
MCF-750 μg/mL[74]
MM9612 μg/mL[74]
NNF80 μg/mL[74]
K56260 μg/mL[74]
EBC-241 (211)HL-6040 μg/mL[74]
HT2980 μg/mL[74]
MCF-740 μg/mL[74]
MM9612 μg/mL[74]
NNF75 μg/mL[74]
K56260 μg/mL[74]
Furanocembranoid 1 (266)BT4747.8 μg/mL[83]
CHAGO7.0 μg/mL[83]
Hep-G25.6 μg/mL[83]
KATO-35.9 μg/mL[83]
SW-6206.3 μg/mL[83]
Furanocembranoid 2 (267)BT4749.5 μg/mL[83]
CHAGO>10 μg/mL[83]
Hep-G2>10 μg/mL[83]
KATO-36.8 μg/mL[83]
SW-6209.9 μg/mL[83]
Furanocembranoid 3 (268)BT4749.6 μg/mL[83]
CHAGO7.1 μg/mL[83]
Hep-G25.7 μg/mL[83]
KATO-38.2 μg/mL[83]
SW-6205.6 μg/mL[83]]
Furanocembranoid 4 (269)BT4749.6 μg/mL[83]
CHAGO9.3 μg/mL[83]
Hep-G26.1 μg/mL[83]
KATO-38.1 μg/mL[83]
SW-6206.0 μg/mL[83]
Laevigatlactone B (272)Hela38.4 μM[84]
(+)-[1R*,2S*,7S*,8S*,12R*]-7,8-Epoxy-2,12-cyclocembra-3E,10Zdien-20,10-olide (276)PEO1132 nM[85]
PEO1TaxR200 nM[85]
(+)-[1R*,4S*,10R*]-4-Hydroxycembra-2E,7E,11Z-trien-20,10-olide (278)PEO1125 nM[85]
PEO1TaxR135 nM[85]
Crotontomentosin A (294)Hela24.0 ± 2.6 μM[88]
Hep G287.9 ± 4.5 μM[88]
MDA-MB-23154.1 ± 2.1 μM[88]
A54940.6 ± 3.9 μM[88]
Crotontomentosin B (295)Hela>100 μM[88]
Hep G228.1 ± 2.1 μM[88]
MDA-MB-23128.7 ± 3.4 μM[88]
A54929.1 ± 5.2 μM[88]
Crotontomentosin C (297)Hela47.9 ± 3.3 μM[88]
Hep G283.3 ± 5.3 μM[88]
MDA-MB-231>100 μM[88]
A549>100 μM[88]]
Crotontomentosin D (296)Hela59.7 ± 4.5 μM[88]
Hep G2>100 μM[88]
MDA-MB-23149.3 ± 2.8 μM[88]
A549>100 μM[88]
Crotolaevigatone B (300)A54921.2 μM[89]
MDA-MB-23133.4 μM[89]
Crotolaevigatone G (305)A54925.6 μM[89]
MDA-MB-23132.7 μM[89]
EBC-324 (311)MCF-740 μM[92]
NFF50 μM[92]
K5626 μM[92]
EBC-329 (312)MCF-713 μM[92]
NFF40 μM[92]
K5620.6 μM[92]
ent-3β-hydroxypimara-8(14),9,15-trien-12-one (319)NFF23 μg/mL[98]
Hela13 μg/mL[98]
HT 2913 μg/mL[98]
MCF-716 μg/mL[98]
MM96L2.8 μg/mL[98]
K56217 μg/mL[98]
EBC-325 (321)MCF-720 μM[99]
NFF6 μM[99]
K5623 μM[99]
EBC-326 (322)MCF-714 μM[99]
NFF6 μM[99]
K5626 μM[99]
EBC-327 (323)MCF-710 μM[99]
NFF10 μM[99]
K56210 μM[99]
3-hydroxycleistantha-13(17),15-diene (325)KATO-36.0 μg/mL[93]
SW-620>10 μg/mL[93]
BT4746.1 μg/mL[93]
Hep-G20.5 μg/mL[93]
CHAGO5.5 μg/mL[93]
3,4-seco-cleistantha-4(18),13(17),15-trien-3-oic acid (326)KATO-39.6 μg/mL[93]
SW-620>10 μg/mL[93]
BT47410 μg/mL[93]
Hep-G28.6 μg/mL[93]
CHAGO>10 μg/mL[93]
Crotobarin (330)KB2.5 ± 0.10 μM[101]
HT292.1 ± 0.60 μM[101]
A5490.79 ± 0.15 μM[101]
HL600.56 ± 0.02 μM[101]
Crotogoudin (331)KB1.5 ± 0.03 μM[101]
HT291.9 ± 0.25 μM[101]
A5490.54 ± 0.02 μM[101]
HL600.49 ± 0.01 μM[101]
Crotonpyrone A (381)Hela10.21 μg/mL[120]
NCI-4466.59 μg/mL[120]
Crotonpyrone B (382)Hela9.54 μg/mL[120]
[1−9-NαC]-crourorb A1 (385)NCI-ADR/RES4.8 μM[123]

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