Study on the absolute configuration and biological activity of rotenoids from the leaves and twigs of Millettia pyrrhocarpa Mattapha, Forest & Hawkins, sp. Nov.

BACKGROUND: M. pyrrhocarpa is a new plant in the Fabaceae: Faboideae family that is found in Thailand. A literature search revealed that the Milletia genus is rich in bioactive compounds possessing a wide range of biological activities. In this study, we aimed to isolate novel bioactive compounds and to study their bioactivities. METHODS: The hexane, ethyl acetate, and methanol extracts from the leaves and twigs of M. pyrrhocarpa were isolated and purified using chromatography techniques. These extracts and pure compounds were tested in vitro for their inhibitory activities against nine strains of bacteria, as well as their anti-HIV-1 virus activity and cytotoxicity against eight cancer cell lines. RESULTS: Three rotenoids, named 6aS, 12aS, 12S-elliptinol (1), 6aS, 12aS, 12S-munduserol (2), dehydromunduserone (3), and crude extracts were evaluated for antibacterial, anti-HIV, and cytotoxic activities. It was found that compounds 1-3 inhibited the growth of nine strains of bacteria, and the best MIC/MBC values were obtained at 3/ > 3 mg/mL. The hexane extract showed anti-HIV-1 RT with the highest %inhibition at 81.27 at 200 mg/mL, while 6aS, 12aS, 12S-elliptinol (1) reduced syncytium formation in 1A2 cells with a maximum EC50 value of 4.48 µM. Furthermore, 6aS, 12aS, 12S-elliptinol (1) showed cytotoxicity against A549 and Hep G2 cells with maximum ED50 values of 2.27 and 3.94 µg/mL. CONCLUSION: This study led to the isolation of constituents with potential for medicinal application, providing compounds (1-3) as lead compounds against nine strains of bacteria. The hexane extract showed the highest %inhibition of HIV-1 virus, Compound 1 showed the best EC50 in reducing syncytium formation in 1A2 cells, and it also showed the best ED50 against human lung adenocarcinoma (A549) and human hepatocellular carcinoma (Hep G2). The isolated compounds from M. pyrrhocarpa offered significant potential for future medicinal application studies.

Krabasinolide A with anti-HIVs activity from the leaves and twigs of Croton krabas.

One new clerodane-type diterpenoid, together with one known, was isolated from the leaves and twigs of C. krabas. The structures of these compounds were elucidated as krabasinolide A (1) and taraxerol (2) by spectroscopic methods (UV, IR, HRESIMS, 1 D, and 2 D NMR), and the relative stereochemistry was confirmed by X-ray diffraction analysis with graphite monochromated Mo-Kα (λ = 0.71073 Å) radiation at 296(2) K. Extracts and compounds 1-2 were evaluated for in vitro antiviral activity.

Two new labdane-type diterpenoids cinnamate from Croton decalvatus Esser.

Two new labdane diterpene derivatives, crotondecalvatin A (1) and crotondecalvatin B (2) were obtained from the leaves and twigs of Croton decalvatus. The structures of compounds were established on the basis of extensive spectroscopic data.

Cytotoxic aporphine alkaloids from leaves and twigs of Pseuduvaria trimera (Craib).

From ethyl acetate-methanol extracts of leaves and twigs of Pseuduvaria trimera a new aporphine alkaloid; 8-hydroxy-1,4,5-trimethoxy-7-oxoaporphine or 8-hydroxyartabonatine C (1) was isolated, together with the known 1,2,3-trimethoxy-4,5-dioxo-6a,7-dehydroaporphine (ouregidione, 2). Their structures were elucidated by a combination of spectral methods; mainly 2D NMR; IR and MS. Compounds 1 and 2 exhibited cytotoxic activity with IC50 values of 26.36±5.18 µM and 12.88±2.49 µM, respectively, for human hepatocellular carcinoma HepG2 cells, and 64.75±4.45 and 67.06±3.5 µM, respectively, for human breast cancer MDA-MB231 cells. Both compounds displayed anti-cancer activity but less than that of doxorubicin; a conventional chemotherapeutic drug, the IC50 levels of which were 2.21±1.72 and 1.83±0.09 µM for HepG2 and MDA-MB231 cells, respectively.

Sawtehtetronenin from Goniothalamus sawtehii and its cytotoxicity.

A new acetogenin has been isolated from the ethyl acetate extract of leaves and twigs of G. sawtehii (Annonaceae). The structure of compound 1 was identified as sawtehtetronenin on the basis of spectral evidence (UV, IR, MS and 1H, and 13C NMR) and by comparison with related compounds. Sawtehtetronenin was found to be cytotoxic to human hepatocellular carcinoma HepG2 and breast cancer MDA-MB231 cells with IC50 values of 79.3 ± 11.9 µM and 108.1 ± 1.5 µM, respectively. Compound 1 was less toxic to both cell lines when compared with camptothecin, a chemotherapeutic drug.

First total syntheses of (+/-)-isopiline, (+/-)-preocoteine, (+/-)-oureguattidine and (+/-)-3-methoxynordomesticine and the biological activities of (+/-)-3-methoxynordomesticine.

A convenient and economical synthesis of 4-hydroxy-2,3-dimethoxybenzaldehyde has been developed. This was used as the starting material for the first total syntheses of (+/-)-isopiline, (+/-)-preocoteine, (+/-)-oureguattidine and (+/-)-3-methoxynordomesticine in which the key step involved formation of ring C of the aporphines by a radical-initiated cyclisation. Although (+/-)-3-methoxynordomesticine possesses weak antimicrobial activity, it inhibits the production of nitric oxide (NO), prostaglandin (PG)E(2), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 and the expression of inducible nitric oxide synthase (iNOS) and cycloxygenase (COX)-2 in macrophages stimulated with LPS in vitro.

Total syntheses of telisatin A, telisatin B and lettowianthine.

Treatment of 1-(2-bromoarylmethyl)-3,4-dihydroisoquinolines with oxalyl chloride and triethylamine gave 1-(2-bromophenyl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-2,3-dione derivatives, for example, 1-(2-bromophenyl)-5,6-dihydro-8,9-dimethoxypyrrolo[2,1-a]isoquinoline-2,3-dione. Radical cyclisation of these derivatives with tributyltin hydride and 1,1-azobis(cyclohexanecarbonitrile) afforded telisatin A, telisatin B and lettowianthine.

Total syntheses of (+/-)-gusanlung a, (+/-)-gusanlung D and 8-oxyberberrubine and the uncertainty concerning the structures of (-)-gusanlung A, (-)-gusanlung D and 8-oxyberberrubine.

(+/-)-Gusanlung A, 8-oxyberberrubine and (+/-)-gusanlung D have been synthesized by radical cyclisation of the corresponding 2-aroyl-1-methylenetetra- hydroisoquinolines. The (1)H and (13)C spectra of (-)-gusanlung D were found to be different from those of synthetic (+/-)-gusanlung D. Careful analyses of the (13)C spectra of (-)-gusanlung A and natural 8-oxyberberrubine also cast doubt on the correctness of the structures previously assigned to these two compounds. (+/-)-Gusanlung A and (+/-)-gusanlung D were inactive against Staphylococcus aureus ATCC25932, Escherichia coli ATCC10536 and Candida albicans ATCC90028.

Total synthesis and antimicrobial activity of +/--laurelliptinhexadecan-1-one and +/--laurelliptinoctadecan-1-one.

The structures previously assigned to (+)-laurelliptinhexadecan-1-one (1a) and (+)-laurelliptinoctadecan-1-one (1b) from Cocculus orbiculatus (L.) DC. (Menispermaceae) have been confirmed by total synthesis of the racemic alkaloids. The key step of the synthesis involved formation of ring C of the aporphines by a radical-intiated cyclisation. Both (+/-)-laurelliptinhexadecan-1-one (1a) and (+/-)-laurelliptinoctadecan-1-one (1b) were inactive against Staphylococcus aureus ATCC25932, Escherichia coli ATCC10536 and Candida albicans ATCC90028.