Lanostane-type Triterpenoids Research Articles

Anti-human Immunodeficiency Virus-1 Protease Activity of New Lanostane-Type Triterpenoids from Ganoderma sinense

Five new highly oxygenated lanostane-type triterpenoids [ganoderic acid GS-1 (1), ganoderic acid GS-2 (2), ganoderic acid GS-3 (3), 20(21)-dehydrolucidenic acid N (4) and 20-hydroxylucidenic acid A (5)] were isolated from the fruiting body of Ganoderma sinense, together with known compounds including 6 triterpenoids and 3 sterols. The structures of the new triterpenoids determined by spectroscopic means including 2D NMR were 7beta-hydroxy-3,11,15-trioxo-lanosta-8,24(E)-dien-26-oic acid (1), 7beta,15alpha-dihydroxy-3,11-dioxo-lanosta-8,24(E)-dien-26-oic acid (2), 12beta-acetoxy-3beta,7beta-dihydroxy-11,15-dioxo-lanosta-8,24(E)-dien-26-oic acid (3), 3beta,7beta-dihydroxy-11,15-dioxo-25,26,27-trinorlanosta-8,20-dien-24-oic acid (4), and 7beta,20xi-dihydroxy-3,11,15-trioxo-25,26,27-trinorlanost-8-en-24-oic acid (5), respectively. Among these, ganoderic acid GS-2, 20-hydroxylucidenic acid N, 20(21)-dehydrolucidenic acid N and ganoderiol F inhibited human immunodeficiency virus-1 protease with IC(50) values of 20-40 microM.

Polyporenic acid C induces caspase‐8‐mediated apoptosis in human lung cancer A549 cells

Lung cancer continues to be the leading cause of cancer-related mortality worldwide. This warrants the search for new and effective agents against lung cancer. We and others have recently shown that lanostane-type triterpenoids isolated from the fungal species Poria cocos (P. cocos) can inhibit cancer growth. However, the mechanisms responsible for the anticancer effects of these triterpenoids remain unclear. In this study, we investigated the effect of polyporenic acid C (PPAC), a lanostane-type triterpenoid from P. cocos, on the growth of A549 nonsmall cell lung cancer cells (NSCLC). The results demonstrate that PPAC significantly reduced cell proliferation via induction of apoptosis as evidenced by sub-G1 analysis, annexin V-FITC staining, and increase in cleavage of procaspase-8, -3, and poly(ADP-ribose)-polymerase (PARP). However, unlike our previously reported lanostane-type triterpenoid, pachymic acid, treatment of cells with PPAC was not accompanied by disruption of mitochondrial membrane potential and increase in cleavage of procaspase-9. Further, PPC-induced apoptosis was inhibited by caspase-8 and pan caspase inhibitors but not by a caspase-9 inhibitor. Taken together, the results suggest that PPAC induces apoptosis through the death receptor-mediated apoptotic pathway where the activation of caspase-8 leads to the direct cleavage of execution caspases without the involvement of the mitochondria. Furthermore, suppressed PI3-kinase/Akt signal pathway and enhanced p53 activation after PPAC treatment suggests this to be an additional mechanism for apoptosis induction. Together, these results encourage further studies of PPAC as a promising candidate for lung cancer therapy.

Structures and Absolute Configurations of Sulfate-Conjugated Triterpenoids Including an Antifungal Chemical Defense of the Green Macroalga Tydemania expeditionis

Cytotoxicity-guided fractionation of the green macroalga Tydemania expeditionis led to isolation of four sulfate-conjugated triterpenoids including one new lanostane-type triterpenoid disulfate, lanosta-8-en-3,29-diol-23-oxo-3,29-disodium sulfate (1), and three known cycloartane-type triterpenoid disulfates, cycloartan-3,29-diol-23-one 3,29-disodium sulfate (2), cycloart-24-en-3,29-diol-23-one 3,29-disodium sulfate (3), and cycloartan-3,23,29-triol 3,29-disodium sulfate (4). Extensive 1D and 2D NMR analyses in combination with X-ray crystallography established the structure and absolute configuration of 1 and allowed determination of the absolute configurations of 2-4 with a revision of previously assigned configuration at C-5. Each natural product was moderately cytotoxic in tumor cell and invertebrate toxicity assays. Of the natural products, only 4 exhibited significant antifungal activity at whole-tissue natural concentrations against the marine pathogen Lindra thalassiae. Comparison of the biological activities of natural products with their desulfated derivatives indicated that sulfation does not appear to confer cytotoxicity or antifungal activity.

Lanostane-Type Triterpenoids from the Roots of Kadsura coccinea

Seven new lanostane-type triterpenoids, seco-coccinic acids A-F (1- 6) and coccinilactone A (7), were isolated from the roots of Kadsura coccinea. Their structures were established on the basis of spectroscopic data analysis. The absolute configuration at C-24 of compound 5 was confirmed by the modified Mosher's method. The cell growth inhibitory effects of these compounds were determined in human leukemia HL-60 cells, and it was found that compounds 1, 2, 3, and 5 exhibited antiproliferative effects with GI 50 values ranging from 6.8 to 42.1 microM.

Lanostane-type triterpenoids from the sclerotia of Inonotus obliquus possessing anti-tumor promoting activity

Two new lanostane-type triterpenoids, 1 and 2 besides two known lanostane-type triterpenoids, 3 and 4 were isolated from the sclerotia of Inonotus obliquus. Their structures were determined to be lanosta-8,23 E-diene-3β,22 R,25-triol ( 1) and lanosta-7:9(11),23 E-triene-3β,22 R,25-triol ( 2) by spectral data. These compounds were tested for their anti-tumor-promoting activity using a short-term in vitro assay for EBV–EA activation induced by TPA. Compounds 1, 2 and 4 were stronger than the positive control, oleanolic acid. The most abundant compound 4 was investigated for the inhibitory effect in a two-stage carcinogenesis test on mouse skin using DMBA as an initiator and TPA as a promoter. Compound 4 was found to exhibit the potent anti-tumor promoting activity in the in vivo carcinogenesis test.

Novel Lanostane and Rearranged Lanostane-Type Triterpenoids from Abies sachalinensis-II-

In the previous work we reported five A-seco-rearranged lanostane triterpenoids as antibacterial constituents from the ethyl acetate soluble fraction of Abies sachalinensei leaves. In further study on the isolation of constituents from the ethyl acetate soluble fraction, two new rearranged lanostane and lanostane-type triterpenoids (3, 4) and three reported compound (1, 2, 5) were isolated. The structures of new compound 3 and 4 were determined to be 3,4-seco-4(28),6,8(14),24-mariesatetraen-26,23-olide-23-hydroxy-3-oic acid and 3,4-seco-4(28),7,24-lanostatrien-26,23-olide-23-hydroxy-3-oic acid, respectively, by spectral studies on HR-MS, (1)H-NMR, (13)C-NMR, and 2D-NMR spectra. Compound 1 was identified with pindrolactone and its structure was revised as 7,14,22Z,24-mariesatetraen-26,23-olide-3alpha-ol. Structures of 2 and 5 were determined as 7,14,24-mariesatrien-26,23-olide-3alpha,23-diol and 3alpha-hydroxy-7,14,24E-mariesatrien-23-oxo-26-oic acid. Of these compounds, 2, 3 and 4 were obtained as lactol tautomer mixtures at gamma-lactone structures of side chains.

Structure determination of inonotsuoxides A and B and in vivo anti-tumor promoting activity of inotodiol from the sclerotia of Inonotus obliquus

Two new lanostane-type triterpenoids, inonotsuoxides A ( 1) and B ( 2) along with three known lanostane-type triterpenoids, inotodiol ( 3), trametenolic acid ( 4), and lanosterol ( 5), were isolated from the sclerotia of Inonotus obliquus (Pers.: Fr.) (Japanese name: Kabanoanakake) (Russian name: Chaga). Their structures were determined to be 22 R,25-epoxylanost-8-ene-3β,24 S-diol ( 1) and 22 S,25-epoxylanost-8-ene-3β,24 S-diol ( 2) on the basis of spectral data including single crystal X-ray analysis. These compounds except for 2 were tested for their inhibitory effects on Epstein–Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. The most abundant triterpene, inotodiol ( 3), was investigated for the inhibitory effect in a two-stage carcinogenesis test on mouse skin using 7,12-dimethylbenz[ a]anthracene (DMBA) as an initiator and TPA as a promoter. Compound 3 was found to exhibit the potent anti-tumor promoting activity in the in vivo carcinogenesis test.

Lanostane Triterpenoids from the Sri Lankan Basidiomycete Ganoderma applanatum

Two new lanostane-type triterpenoids, 3alpha,16alpha-dihydroxylanosta-7,9(11),24-trien-21-oic acid (1) and 3alpha,16alpha,26-trihydroxylanosta-7,9(11),24-trien-21-oic acid (2), along with three known lanostanoids, 16alpha-hydroxy-3-oxolanosta-7,9(11),24-trien-21-oic acid (3), 3alpha-carboxyacetoxy-24-methylen-23-oxolanost-8-en-26-oic acid (4), and 3alpha-carboxyacetoxy-24-methyl-23-oxolanost-8-en-26-oic acid (5), have been isolated from the EtOAc extract of the fruiting body of Ganoderma applanatum. The structures of 1, 2, and 3 were determined directly by the interpretation of spectroscopic data, while the structures of 4 and 5 were assigned by comparison of spectroscopic data against literature values.

Lanostane triterpenoids from the inedible mushroom Fomitopsis spraguei

Investigation of the methanolic extract of the inedible mushroom Fomitopsis spraguei (Polyporaceae) led to the isolation of five lanostane-type triterpenoids ( 1– 5): three new compounds named fomitopsins A–C ( 2– 4), and two known compounds, quercinic acid C ( 1) and 3α-carboxyacetyl-12β-hydroxyquercinic acid ( 5). Their structures were determined by 2D NMR, MS, IR, UV spectra, and X-ray crystallographic analyses. An X-ray crystal structure analysis of quercinic acid C ( 1) established its stereochemistry as 3 R,12 R-dihydroxy-24 R-methyl-23-oxo-25 S-lanost-8-en-26-oic acid.

Synthetic lanostane-type triterpenoids as inhibitors of DNA topoisomerase II

DNA topoisomerase (Topo) II is one of the target enzymes for chemotherapeutic drug development. Lanostane-type triterpenoids with various functional groups (–Cl, –Br, –OMe, –CHO, –CN, –COOH, and –COOMe) at C-2 were synthesized from 3-oxolanost-9(11)-en-24 S,25-diol ( 9) isolated from Pinus luchuensis and their inhibitory effects on Topo II activity and cytotoxic activities against A549 cells were examined. All the derivatives showed Topo II inhibitory effects with IC 50 values ranging from 1.86 to 149.97 μM and cytotoxic activities with ED 50 values ranging from 3.96 to 38.15 μM.

Two Lanostane Triterpenoids from Abies koreana.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Two lanostane triterpenoids from Abies koreana

Two lanostane-type triterpenoids, namely, 24( E)-3,4-seco-9β H-lanosta-4(28),7,24-triene-3,26-dioic acid and 24( E)-3-oxo-9β H-lanosta-7,24-dien-26-ol were isolated from the root bark of Abies koreana. Their structures were established based on spectroscopic analyses. Compound 2 exhibited marginal cytotoxicity against human tumor cell lines.

A bioactive triterpenoid and vulpinic acid derivatives from the mushroom Scleroderma citrinum.

A new lanostane-type triterpenoid, (20 S,22 S,23 E)-22- O-acetyl-25-hydroxylanosta-8,23( E)-dien-3-one ( 1), isolated as a new natural product for the first time, methyl 4,4'-dimethoxyvulpinate ( 2), together with the known compound 4,4'-dimethoxyvulpinic acid ( 3) were isolated from the mushroom Scleroderma citrinum. Their structures were determined using spectroscopic and chemical methods, and an X-ray analysis was performed to confirm structure of 1. Compound 1 exhibited significant antiviral activity against Herpes simplex type 1. Compound 3 and two of its derivatives, the dibromo derivative 5 and acetate derivative 6, exhibited activity towards Mycobacterium tuberculosis. In addition, 5 and 6 also showed cytotoxicity against the NCI-H187 cell line.

Triterpenoid constituents isolated from the bark of Abies sachalinensis.

Three new lanostane-type triterpenoids (1-3) were isolated from the bark of Abies sachalinensis along with a known compound (4). The structures of 1-4 were characterized by spectroscopic methods including NMR and MS. Compound 4 and some derivatives were tested for inhibitory effects on in vitro DNA topoisomerases I and II and found to be selective catalytic inhibitors of topoisomerase II activity with IC(50) values in the range 43-76 microM.

New 9β-Lanostane-Type Triterpenic and 13,14-seco-Steroidal Esters from the Roots of Artemisia scoparia

Phytochemical studies on the roots of Artemisia scoparia, collected from the Kullu Valley region of Himachal Pradesh, India, resulted in the isolation of one lanostane-type triterpenoid 1 and two 1...

Ascosteroside, a new antifungal agent from Ascotricha amphitricha. II. Isolation and structure elucidation.

The novel antifungal agent ascosteroside (1) was isolated from cultured broth of Ascotricha amphitricha (ATCC 74237). The structure based on spectroscopic data was determined to be an alpha-linked glycoside of a lanostane-type triterpenoid.

Ganoderiol A and B, New Triterpenoids from the FungusGanoderma lucidum(Reishi)

Two new lanostane-type triterpenoids, ganoderiol A (1) and ganoderiol B (2) were isolated from the fruiting bodies of Ganoderma lucidum, together with known ganodermanontriol (3) and ganodermatriol (4). The compounds were identified as 5α-lanosta-7,9(11)-dien-3β,24,25,26-tetraol (1), 15α,26,27-trihydroxy-5α-lanosta-7,9(11),24-trien-3-one (2), 24,25,26-trihydroxy-5α-lanosta-7,9(11)-dien-3-one (3) and 5α-lanosta-7,9(ll),24-trien-3β,26,27-triol (4), respectively.

Ganoderic acid derivatives, highly oxygenated lanostane-type triterpenoids, from Ganoderma lucidum

The structures of two new compounds, ganoderic acids E and F, isolated in the form of their methyl esters from the fruit body of the fungus Ganoderma lucidum have been elucidated as 3β,7β,15α-trihydroxy-11,23-dioxo-5α-lanost-8-en-26-oic acid and 3,7,11,15,23-pentaoxo-5α-lanost-8-en-26-oic acid, respectively.

Ganoderiol A and B, new triterpenoids from the fungus Ganoderma lucidum (Reishi).

Two new lanostane-type triterpenoids, ganoderiol A (1) and ganoderiol B (2) were isolated from the fruiting bodies of Ganoderma lucidum, together with known ganodermanontriol (3) and ganodermatriol (4). The compounds were identified as 5α-lanosta-7,9(11)-dien-3β,24,25,26-tetraol (1), 15α,26,27-trihydroxy-5α-lanosta-7,9(11),24-trien-3-one (2), 24,25,26-trihydroxy-5α-lanosta-7,9(11)-dien-3-one (3) and 5α-lanosta-7,9(ll),24-trien-3β,26,27-triol (4), respectively.

Ganoderic acids T, S and R, new triterpenoids from the cultured mycelia of Ganoderma lucidum.

New lanostane-type triterpenoids, ganoderic acids T, S and R were isolated from the cultured mycelia of Ganoderma lucidum. The structure of ganoderic acid T was determined by the spectral data and X-ray analysis, and the structures of the other compounds were elucidated on the basis of their spectral data.