Search Results (14)

Michael acceptors, such as chalcones and benzylidenes, are privileged scaffolds for the development of anticancer agents. Taking this into account, we developed a selective Claisen–Schmidt condensation of the dammarane-type triterpenoid hollongdione with pyridine-2-carbaldehyde, enabling controlled synthesis of mono- and bis-substituted triterpenes depending on the reaction conditions. The reaction demonstrated high temperature-dependent regioselectivity, providing C2-mono- 2 or 2,21-bis-substituted 3 triterpenes with yields up to 96% and 95%, respectively. The structures of the newly synthesized triterpene chalcones were elucidated by 1D and 2D NMR spectroscopy and unambiguously confirmed by a single-crystal X-ray diffraction, which established the E configuration of the exocyclic double bond. In biological studies, the bis-2-pyridylidene derivative 3 exhibited a pronounced and broad-spectrum antitumor activity in the NCI-60 panel, inducing cell death in 58 of 59 cancer cell lines. High selectivity toward melanoma, renal, and prostate cancer cell lines was observed, with selectivity indices (SI) of up to 18.82 for melanoma LOX IMVI. In MTT assays, compound 3 displayed a submicromolar cytotoxicity, particularly against the KRAS-mutant PANC-1 cell line (IC₅₀ = 0.22 µM). Anticancer activity was further confirmed in a zebrafish (Danio rerio) xenograft model of human HCT116 colon cancer, where tumor growth inhibition reached 72% without pronounced embryotoxicity (LC₅₀ = 1.4 µM). We have developed an efficient approach for the site-selective modification of hollongdione, providing access to potent anticancer dammarane-type chalcones. The bis-2-pyridylidene derivative 3 emerged as a promising lead compound, demonstrating submicromolar potency, high selectivity towards melanoma, and significant in vivo efficacy in a zebrafish xenograft model. Full article

Gynostemma pentaphyllum is a traditional Chinese medicinal plant of considerable application value and commercial potential, primarily due to its production of various bioactive compounds, particularly dammarane-type triterpenoid saponins that are structurally analogous to ginsenosides. Oxidosqualene cyclase (OSC), a pivotal enzyme in the biosynthesis of triterpenoid metabolites in plants, catalyzes the conversion of oxidosqualene into triterpenoid precursors, which are essential components of the secondary metabolites found in G. pentaphyllum. To elucidate the role of OSC gene family members in the synthesis of gypenosides within G. pentaphyllum, this study undertook a comprehensive genome-wide identification and characterization of OSC genes within G. pentaphyllum and compared their expression levels across populations distributed over different geographical regions by both transcriptome sequencing and qRT-PCR experimental validation. The results identified a total of 11 members of the OSC gene family within the genome of G. pentaphyllum. These genes encode proteins ranging from 356 to 767 amino acids, exhibiting minor variations in their physicochemical properties, and are localized in peroxisomes, cytoplasm, plasma membranes, and lysosomes. All GpOSCs contain highly conserved DCTAE and QW sequences that are characteristic of the OSC gene family. A phylogenetic analysis categorized the GpOSCs into four distinct subfamilies. A cis-element analysis of the GpOSC promoters revealed a substantial number of abiotic stress-related elements, indicating that these genes may respond to drought conditions, low temperatures, and anaerobic environments, thus potentially contributing to the stress resistance observed in G. pentaphyllum. Expression analyses across different G. pentaphyllum populations demonstrated significant variability in OSC gene expression among geographically diverse samples of G. pentaphyllum, likely attributable to genetic variation or external factors such as environmental conditions and soil composition. These differences may lead to the synthesis of various types of gypenosides within geographically distinct G. pentaphyllum populations. The findings from this study enhance our understanding of both the evolutionary history of the OSC gene family in G. pentaphyllum and the biosynthetic mechanisms underlying triterpenoid compounds. This knowledge is essential for investigating molecular mechanisms involved in forming dammarane-type triterpenoid saponins as well as comprehending geographical variations within G. pentaphyllum populations. Furthermore, this research lays a foundation for employing plant genetic engineering techniques aimed at increasing gypenoside content. Full article

Despite unquestionable advances in therapy, melanoma is still characterized by a high mortality rate. For years, high expectations have been raised by compounds of natural origin as a component of pharmacotherapy, particularly by triterpenes found in the bark of birch trees. In this study, 3,4-seco-dammara-4(29),20(21),24(25)-trien-3-oic acid (SDT) was isolated from buds of silver birch and its mechanisms of cell death induction, including apoptosis and autophagy, were determined. Cytotoxicity of SDT was evaluated by the cell viability test and clonogenic assay, whereas induction of apoptosis and autophagy was determined by annexin V staining and Western blot. The results revealed dose- and time-dependent reductions in viability of melanoma cells. Treatment of cells for 48 h led to an increase in the percentage of annexin V-positive cells, activation of caspase-8, caspase-9, and caspase-3, and cleavage of PARP, confirming apoptosis. Simultaneously, it was found that SDT increased the level of autophagy marker LC3-II and initiator of autophagy beclin-1. Pretreatment of cells with caspase-3 inhibitor or autophagy inhibitor significantly reduced the cytotoxicity of SDT and revealed that both apoptosis and autophagy contribute to a decrease in cell viability. These findings suggest that 3,4-seco-dammaranes may become a promising group of natural compounds for searching for anti-melanoma agents. Full article

Chikungunya fever, a debilitating disease caused by Chikungunya virus (CHIKV), is characterized by a high fever of sudden onset and an intense arthralgia that impairs individual regular activities. Although most symptoms are self-limited, long-term persistent arthralgia is observed in 30–40% of infected individuals. Currently, there is no vaccine or specific treatment against CHIKV infection, so there is an urgent need for the discovery of new therapeutic options for CHIKF chronic cases. This present study aims to test the antiviral, cytoprotective, and anti-inflammatory activities of an ethanol extract (FF72) from Ampelozizyphus amazonicus Ducke wood, chemically characterized using mass spectrometry, which indicated the major presence of dammarane-type triterpenoid saponins. The major saponin in the extract, with a deprotonated molecule ion m/z 897 [M-H]⁻, was tentatively assigned as a jujubogenin triglycoside, a dammarane-type triterpenoid saponin. Treatment with FF72 resulted in a significant reduction in both virus replication and the production of infective virions in BHK-21-infected cells. The viability of infected cells was assessed using an MTT, and the result indicated that FF72 treatment was able to revert the toxicity mediated by CHIKV infection. In addition, FF72 had a direct effect on CHIKV, since the infectivity was completely abolished in the presence of the extract. FF72 treatment also reduced the expression of the major pro-inflammatory mediators overexpressed during CHIKV infection, such as IL-1β, IL-6, IL-8, and MCP-1. Overall, the present study elucidates the potential of FF72 to become a promising candidate of herbal medicine for alphaviruses infections. Full article

Aglaia cucullata is a mangrove plant with a tropical Asian distribution. It is used as traditional medicine for the treatment of diarrhea, inflammation, skin diseases, and heart diseases. Several compounds isolated from A. cucullata have demonstrated cytotoxic activity against various human cancer cells. Cancer therapies such as surgery, chemo-, and radiotherapy have many side effects. However, the use of natural bioactive compounds such as triterpenoid in cancer treatment can be used as an alternative to reduce these side effects. Therefore, the discovery of bioactive compounds from plants is very important to improve aspects of discovery and development of sustainable new anticancer drug candidates. Here, we report the chemical structures of seven known dammarane-type triterpenoids (1–7) isolated from A. cucullata exocarp and evaluate their cytotoxicity against B16-F10 melanoma skin cancer cells. The isolated compounds included cabraleahydroxylactone 3α-acetate (1), (20S)-20-hydroxydammar,24-en-3α-ol (2), (20S)-20-hydroxydammar,24-en-3-on (3), methyl 20(S)-hydroxy-3,4-secodammar-4(28),24-diene-3-oic acid (4), 3-epi ocotillol II (5), cabraleone (6), and ocotillone (7). The n-hexane extract was found to be active against B16-F10 cells, exhibiting an IC₅₀ value of 7.85 ± 0.22 µg/mL. Fractionation of this extract subsequently identified the compound (20S)-20-hydroxydammar 24-en-3-on (3) as an active substance with an IC₅₀ value of 21.55 ± 0.25 µM, comparing favorably with the positive control cisplatin (12.90 µg/mL; 43.00 µM). These results provide further evidence of the genus Aglaia as a source of cytotoxic cancer drug leads. In addition, compound 3 has potential as a convincing therapeutic agent for further research in the context of sustainable drug development, especially the development of new safe cancer chemotherapeutic agents. Full article

The Aglaia genus, a member of the Meliaceae family, is generally recognized to include a number of secondary metabolite compounds with diverse structures and biological activities, including triterpenoids. Among the members of this genus, Aglaia cucullata has been reported to have unique properties and thrives exclusively in mangrove ecosystems. This plant is also known to contain various metabolites, such as flavaglines, bisamides, and diterpenoids, but there are limited reports on the isolation of triterpenoid compounds from its stem bark. Therefore, this research attempted to isolate and elucidate seven triterpenoids belonging to dammarane-type (1–7) from the stem bark of Aglaia cucullata. The isolated compounds included 20S,24S-epoxy-3α,25-dihydroxy-dammarane (1), dammaradienone (2), 20S-hydroxy-dammar-24-en-3-on (3), eichlerianic acid (4), (20S,24RS)-23,24-epoxy-24-methoxy-25,26,27-tris-nor dammar-3-one (5), 3α-acetyl-cabraleahydroxy lactone (6), and 3α-acetyl-20S,24S-epoxy-3α,25-dihydroxydammarane (7). Employing spectroscopic techniques, the chemical structures of the triterpenoids were identified using FTIR, NMR, and HRESITOF-MS. The cytotoxic activity of compounds 1–7 was tested with the PrestoBlue cell viability reagent against MCF-7 breast cancer, B16-F10 melanoma, and CV-1 normal kidney fibroblast cell lines. The results displayed that compound 5 had the highest level of bioactivity compared to the others. Furthermore, the IC₅₀ values obtained were more than 100 μM, indicating the low potential of natural dammarane-type triterpenoids as anticancer agents. These findings provided opportunities for further studies aiming to increase their cytotoxic activities through semi-synthetic methods. Full article

Four new dammarane triterpenoid saponins cypaliurusides Z₁–Z₄ (1–4) and eight known analogs (5–12) were isolated from the leaves of Cyclocarya paliurus. The structures of the isolated compounds were determined using a comprehensive analysis of 1D and 2D NMR and HRESIMS data. The docking study demonstrated that compound 10 strongly bonded with PTP1B (a potential drug target for the treatment of type-II diabetes and obesity), hydrogen bonds, and hydrophobic interactions, verifying the importance of sugar unit. The effects of the isolates on insulin-stimulated glucose uptake in 3T3-L1 adipocytes were evaluated and three dammarane triterpenoid saponins (6, 7 and 10) were found to enhance insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Furthermore, compounds 6, 7, and 10 exhibited potent abilities to promote insulin-stimulated glucose uptake in 3T3-L1 adipocytes in a dose-dependent manner. Thus, the abundant dammarane triterpenoid saponins from C. paliurus leaves exhibited stimulatory effects on glucose uptake with application potential as a antidiabetic treatment. Full article

Two new dammarane-type triterpenoid fatty acid ester derivatives, 3β-oleate-20S-hydroxydammar-24-en (1) and 3β-oleate-20S,24S-epoxy-25-hydroxydammarane (2) with a known dammarane-type triterpenoid compound, such as 20S-hydroxydammar-24-en-3-on (3), were isolated from the stem bark of Aglaiaelliptica (C.DC.) Blume. The chemical structures were determined by spectroscopic methods, including FTIR, NMR (one and two-dimensional), and HRESITOF-MS analysis, as well as chemical derivatization and comparison with previous literature. Furthermore, the synthetic analog resulting from transesterification of 1 and 2 also obtained 3β,20S-dihydroxy-dammar-24-en (4) and 20S,24S-epoxy-3β,25-dihydroxydammarane (5), respectively. The cytotoxic effect of all isolated and synthetic analog compounds was evaluated using PrestoBlue reagent against MCF-7 breast cancer cell and B16-F10 melanoma cell lines. The 20S-hydroxydammar-24-en-3-on (3) showed the strongest activity against MCF-7 breast cancer and B16-F10 melanoma cell, indicating that the ketone group at C-3 in 3 plays an essential role in the cytotoxicity of dammarane-type triterpenoid. On the other hand, compounds 1 and 2 had very weak cytotoxic activity against the two cell lines, indicating the presence of fatty acid, significantly decreasing cytotoxic activity. This showed the significance of the discovery to investigate the essential structural feature in dammarane-type triterpenoid, specifically for the future development of anticancer drugs. Full article

Triterpenoids, important secondary plant metabolites made up of six isoprene units, are found widely in higher plants and are studied for their structural variety and wide range of bioactivities, including antiviral, antioxidant, anticancer, and anti-inflammatory properties. Numerous studies have demonstrated that different triterpenoids have the potential to behave as potential antiviral agents. The antiviral activities of triterpenoids and their derivatives are summarized in this review, with examples of oleanane, ursane, lupane, dammarane, lanostane, and cycloartane triterpenoids. We concentrated on the tetracyclic and pentacyclic triterpenoids in particular. Furthermore, the particular viral types and possible methods, such as anti-human immunodeficiency virus (HIV), anti-influenza virus, and anti-hepatitis virus, are presented in this article. This review gives an overview and a discussion of triterpenoids as potential antiviral agents. Full article

The search for new bioactive compounds from plant sources has been and continues to be one of the most important fields of research in drug discovery. However, Natural Products research has continuously evolved, and more and more has gained a multidisciplinary character. Despite new developments of methodologies and concepts, one intriguing aspect still persists, i.e., different species belonging to the same genus can produce different secondary metabolites, whereas taxonomically different genera can produce the same compounds. The genus Salvia L. (Family Lamiaceae) comprises myriad distinct medicinal herbs used in traditional medicine worldwide that show different pharmacological activities due to the presence of a variety of interesting specialized metabolites, including mono-, sesqui-, di-, sester-, tri-, tetra-, and higher terpenoids as well as phenylpropanoids, phenolic acid derivatives, lignans, flavonoids, and alkaloids. We herein summarize the research progress on some uncommon terpenoids, isolated from members of the genus Salvia, which are well recognized for their potential pharmacological activities. This review also provides a current knowledge on the biosynthesis and occurrence of some interesting phytochemicals from Salvia species, viz. C₂₃-terpenoids, sesterterpenoids (C₂₅), dammarane triterpenoids (C₃₀), and uncommon triterpenoids (C₂₀+C₁₀). The study was carried out by searching various scientific databases, including Elsevier, ACS publications, Taylor and Francis, Wiley Online Library, MDPI, Springer, Thieme, and ProQuest. Therefore, 106 uncommon terpenoids were identified and summarized. Some of these compounds possessed a variety of pharmacological properties, such as antibacterial, antiviral, antiparasitic, cytotoxic and tubulin tyrosine ligase inhibitory activities. Due to the lack of pharmacological information for the presented compounds gathered from previous studies, biological investigation of these compounds should be reinvestigated. Full article

Inflammation is a very common and important pathological process that can cause many diseases. The discovery of anti-inflammatory drugs and the treatment of inflammation are particularly essential. Dammarane-type triterpenoid saponins (PNS) were demonstrated to show anti-inflammatory effects in the leaves of Panax notoginseng. Chromatographies and spectral analysis methods were combined to isolate and identify PNS. Moreover, the nitric oxide (NO) inhibitory activities of all compounds were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. As a result, eleven new dammarane-type triterpenoid saponins, notoginsenosides NL-A₁–NL-A₄ (1–4), NL-B₁–NL-B₃ (5–7), NL-C₁–NL-C₃ (8–10), and NL-D (11) were isolated, and their structures were identified by using various spectrometric techniques and chemical reactions. Among them, compounds 4 and 11 were characterized by the malonyl substitution at 3-position. The 3-malonyl substituted dammarane-type terpennoids were first obtained from natural products. In addition, compounds 1, 2, 5, 6, and 8–10 were found to play an important role in suppressing NO levels at 50 μM, without cytotoxicity. All inhibitory activities were found to be dose-dependent. Full article

Panax ginseng Meyer cv. Silvatica (PGS), which is also known as “Lin-Xia-Shan-Shen” or “Zi-Hai” in China, is grown in forests and mountains by broadcasting the seeds of ginseng and is harvested at the cultivation age of 15–20 years. In this study, four new dammarane-type triterpenoids, ginsengenin-S1 (1), ginsengenin-S2 (2), ginsenoside-S3 (3), ginsenoside-S4 (4), along with one known compound were isolated from pearl knots of PGS. Ginsengenin-S2 significantly alleviated oxidative damage when A549 cells were exposed to cigarette smoke (CS) extract. In addition, ginsengenin-S2 could inhibit the CS-induced inflammatory reaction in A549 cells. Protective effects of ginsengenin-S2 against CS-mediated oxidative stress and the inflammatory response in A549 cells may involve the Nrf2 and HDAC2 pathways. Full article

Dammarane-type triterpenoids (DTT) widely distribute in various medicinal plants. They have generated a great amount of interest in the field of new drug research and development. Generally, DTT are the main bioactive ingredients abundant in Araliaceae plants, such as Panax ginseng, P. japonicas, P. notoginseng, and P. quinquefolium. Aside from Araliaceae, DTT also distribute in other families, including Betulaceae, Cucurbitaceae, Meliaceae, Rhamnaceae, and Scrophulariaceae. Until now, about 136 species belonging to 46 families have been reported to contain DTT. In this article, the genus classifications of plant sources of the botanicals that contain DTT are reviewed, with particular focus on the NMR spectral features and pharmacological activities based on literature reports, which may be benefit for the development of new drugs or food additives. Full article

Among the classes of identified natural products, triterpenoids, one of the largest families, have been studied extensively for their diverse structures and variety of biological activities, including antitumor effects. In the present study, a phytochemical study of the green walnut husks of Juglans mandshurica Maxim led to the isolation of a new dammarane triterpene, 12β, 20(R), 24(R)-trihydroxydammar-25-en-3-one (6), together with sixteen known compounds, chiefly from chloroform and ethyl acetate extracts. According to their structural characteristics, these compounds were divided into dammarane-type, oleanane- and ursane-type. Dammarane-type triterpenoids were isolated for the first time from the Juglans genus. As part of our continuing search for biologically active compounds from this plant, all of these compounds were also evaluated for their cytotoxic activities against the growth of human cancer cells lines HepG-2 by the MTT assay. The results were shown that 20(S)-protopanaxadiol, 2α,3β,23-trihydroxyolean-12-en-28-oic acid and 2α,3β,23-trihydroxyurs-12-en-28-oic acid exhibited better cytotoxicity in vitro with IC₅₀ values of 10.32 ± 1.13, 16.13 ± 3.83, 15.97 ± 2.47 μM, respectively. Preliminary structure-activity relationships for these compounds were discussed. Full article