Cytotoxic, antitopoisomerase IIα, and anti-HIV-1 activities of triterpenoids isolated from leaves and twigs of Gardenia carinata.

Eight new cycloartane triterpenoids (1-8), named carinatins A-H, and the known compounds secaubryolide (9) and dikamaliartane D (10) were isolated from the leaves and twigs of Gardenia carinata. Their structures were determined on the basis of spectroscopic methods. Cytotoxic, antitopoisomerase IIα, and anti-HIV-1 activities of compounds 1-7, 9, and 10 were investigated.

DNA topoisomerase IIα inhibitory and anti-HIV-1 flavones from leaves and twigs of Gardenia carinata.

Four new flavones, 5,2'-dihydroxy-7,3',4',5'-tetramethoxyflavone (1), 5,2',5'-trihydroxy-7,3',4'-trimethoxyflavone (2), 5,7,2',5'-tetrahydroxy-6,3',4'-trimethoxyflavone (3) and 5,2',5'-trihydroxy-6,7,3',4'-tetramethoxyflavone (4), along with the known 5,3'-dihydroxy-6,7,4',5'-tetramethoxyflavone (5), 5,7,3',5'-tetrahydroxy-6,4'-dimethoxyflavone (6), syringaldehyde, vanillic acid and scopoletin were isolated from the leaves and twigs of Gardenia carinata (Rubiaceae). Their structures were determined by spectroscopic methods. Flavone 2 exhibited cytotoxic activity against P-388 and MCF-7 cell lines, while 3, 5 and 6 were active only in P-388 cell line. All active compounds were found to inhibit DNA topoisomerase IIα activity, which may be responsible for the observed cytotoxicity. Flavones 1-3, 5 and 6 also exhibited anti-HIV-1 activity in the anti-syncytium assay using (∆Tat/rev)MC99 virus and 1A2 cell line system; 2 was most potent. Only flavones 1 and 6 showed considerably activity against HIV-1 reverse transcriptase.

A new conjugated amide-dimer from the aerial parts of Piper submultinerve.

Bioassay-guided fractionation and purification of the aerial parts of Piper submultinerve led to the isolation of a new conjugated amide-dimer, submultinamide A (1), along with 11 known compounds. The structures were determined on the basis of spectroscopic methods. Among the tested compounds, pellitorine (2), guineensine (4), N-benzylcinnamide (6) and aristolactam BII (8) showed significant activities in the anti-syncytium assay using (ΔTat/Rev)MC99 virus and 1A2 cell line system, whereas 2 was most active (EC50 35.1 µM and selectivity index 4.7). In the HIV-1 reverse transcriptase assay, only 4 was active with IC50 50.8 µM.

A new diarylheptanoid from the rhizomes of Zingiber mekongense.

A new diarylheptanoid, (3S,5S)-3,5-diacetoxy-1,7-bis(3,4,5-trimethoxyphenyl)heptane (1), together with the known docosyl trans-ferulate (2), (1S,2S,4S)-p-menthan-1,2,4-triol (3), 5αH-eudesmane-4α,11-diol (4), 5αH-eudesmane-4ß,11-diol (5), 4α,10ß-dihydroxy-1ßH,5αH-guaia-6-ene (guaianediol) (6), (+)-galanolactone (7), (E)-labda-8(17),12(13)-dien-15,16-olide (8), labda-8(17),13(14)-dien-15,16-olide (9), 3,5-dihydroxy-7,4'-dimethoxyflavone (10) and 3,5,3'-trihydroxy-7,4'-dimethoxyflavone (11) were isolated from the rhizomes of Zingiber mekongense. Their structures were determined by spectroscopic methods. The stereochemistry of 1 was proved through chemical conversion. Compounds 1, 4-7 and 9-11 exhibited anti-HIV-1 activities in the anti-syncytium assay using (∆Tat/rev)MC99 virus and 1A2 cell line system, while only compounds 7 and 11 were found active in the HIV-1 reverse transcriptase assay.

Thai Acanthamoeba isolate (T4) induced apoptotic death in neuroblastoma cells via the Bax-mediated pathway.

A Thai Acanthamoeba isolate named AS recovered from a corneal scraping of a keratitis patient was genotypically determined as T4. AS trophozoites were used for studying Acanthamoeba-induced apoptosis in mouse neuroblastoma NA cells during in vitro co-cultivation. The Acanthamoeba-exposed NA cells showed signs of apoptosis including cell shrinkage, nuclear condensation and DNA fragmentation. The effect was confirmed by DNA laddering electrophoresis. Involvement of caspase enzymes and mitochondrial pro- and anti-apoptotic proteins (Bax and Bcl-2) in AS-induced apoptosis was determined. The use of Z-VAD-FMK, a pan-caspase inhibitor, significantly reduced the apoptotic effect, while Bax/Bcl-2 ratio analysis showed a significant increase in the expression of apoptotic proteins in AS-exposed NA cells. These results strongly indicated that apoptosis induced by AS trophozoites is caspase-dependent and is mediated by over-expression of pro-apoptotic proteins in the mitochondrial pathway. This is the first report on the role of Bax in mediating apoptosis induced by Acanthamoeba.

Anti-HIV-1 diterpenoids from leaves and twigs of Polyalthia sclerophylla.

Bioassay-guided fractionation and purification of the anti-HIV-1-active MeOH extract from the leaves and twigs of Polyalthia sclerophylla led to the isolation of two new compounds, ENT-kaur-sclerodimer ( 1) and cyclotucanol 3-palmitate ( 2), along with the known ENT-kaur-16-en-19-oic acid ( 3), 15 beta-hydroxy- ENT-kaur-16-en-19-oic acid ( 4), 15 beta-acetoxy- ENT-kaur-16-en-19-oic acid ( 5), 15-oxo- ENT-kaur-16-en-19-oic acid ( 6), 16 alpha,17-dihydroxy- ENT-kauran-19-oic acid ( 7), 16 alpha-hydroxy- ENT-kauran-19-oic acid (xylopic acid) ( 8), a pseudodimer (15 alpha-hydroxy- ENT-kaur-16-en-19-oic acid/17-hydroxy- ENT-kaur-15-en-19-oic acid) ( 9), ermanin, nicotiflorin, and allantoin. Among these isolates, compound 3 was the most active in both anti-syncytium (EC (50) 13.7 microg/mL and selectivity index 3.1) and HIV-1 reverse transcriptase (IC (50) 34.1 microg/mL) assays.

Dichapetalin-type triterpenoids and lignans from the aerial parts of Phyllanthus acutissima.

Chemical investigation of the aerial parts of Phyllanthus acutissima resulted in the isolation of five new dichapetalin-type triterpenoids, acutissimatriterpenes A-E ( 1- 5), and two new lignans, acutissimalignans A ( 6) and B ( 7), along with two known lignans and three known ellagic acid derivatives. The structures of 1- 7 were determined mainly on the basis of spectroscopic methods. The compounds obtained were evaluated for cytotoxic and anti-HIV-1 activities.

Anti HIV-1 flavonoid glycosides from Ochna integerrima.

Bioassay-guided fractionation of the anti-HIV-1 active EtOAc extract from leaves and twigs of Ochna integerrima led to the isolation of five new flavonoid glycosides 1 - 5, five known flavonoids 6 - 10, and two known flavonoid glycosides 11 and 12. Structures were determined based on spectroscopic analyses. 6- gamma, gamma-Dimethylallyldihydrokaempferol 7- O- beta-D-glucoside (1), 6-gamma, gamma-dimethylallylquercetin 7- O- beta- D-glucoside (3), 6-(3-hydroxy-3-methylbutyl)taxifolin 7- O- beta-D-glucoside (4), 6-(3-hydroxy-3-methylbutyl)quercetin 7- O-beta-D-glucoside (5), and 6-gamma, gamma-dimethylallyltaxifolin 7-O-beta-D-glucoside (11) showed anti-HIV-1 activities in the syncytium assay using the (Delta Tat/rev)MC99 virus and the 1A2 cell line system with EC(50) values ranging from 14.0 - 102.4 microg/mL. Furthermore, ochnaflavone 7''-O-methyl ether (7) and 2'', 3''-dihydroochnaflavone 7''-O-methyl ether (8) were very active; they exerted activities in the syncytium assay with EC(50) values of 2.0 and 0.9 microg/mL, respectively, and likewise inhibited HIV-1 reverse transcriptase (RT) with IC(50) values of 2.0 and 2.4 microg/mL, respectively.