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Resveratrol has been shown to have anticarcinogenic activity. We previously found that resveratrol inhibited growth and induced apoptosis in 2 human melanoma cell lines. In this study we determined whether resveratrol would inhibit human melanoma xenograft growth. Athymic mice received control diets or diets containing 110 [micro]mol/L or 263 [micro]mol/L resveratrol, 2 wk prior to subcutaneous injection of the tumor cells. Tumor growth was measured during a 3-wk period. Metabolism of resveratrol was assayed by bolus gavage of 75 mg/kg resveratrol in tumor-bearing and nontumor-bearing mice. Pellets containing 10-100 mg resveratrol were implanted into the mice, next to newly palpated tumors, and tumor growth determined. We also determined the effect of a major resveratrol metabolite, piceatannol, on experimental lung metastasis. Resveratrol, at any concentration tested, did not have a statistically significant effect on tumor growth. The higher levels of resveratrol tested (0.006% in food or 100mg in slow-release pellets) tended to stimulate tumor growth (P = 0.08-0.09). Resveratrol and its major metabolites, resveratrol glucuronide and piceatannol, were found in serum, liver, skin, and tumor tissue. Piceatannol did not affect the in vitro growth of a murine melanoma cell line, but significantly stimulated the number of lung metastases when these melanoma cells were directly injected into the tail vein of the mouse. These results suggest that resveratrol is not likely to be useful in the treatment of melanoma and that the effects of phytochemicals on cell cultures may not translate to the whole animal system.

Several bioactive steroidal compounds isolated from the 'Melia volkensii' family are presented. The compounds (E)-volkendousin, 2,19-oxymeliavosin and (Z)-volkendousin were isolated as white needles. On the other hand, meliavosin was isolated as white prisms. Test showed the activeness and cytotoxicity of (E)-volkendousin and the relatively weak activities of the remaining compounds.

A study was conducted on membrane conformations in relation to cytotoxicity of asimicin and its analogues. The results indicate that the tetrahydrofuran (THF) rings of acetogenins are located near the polar interfacial head group region of the DMPC. The findings also suggest that an asimicin-type acetogenin can either exhibit sickle-shaped or U-shaped conformations, depending on the length of the alkyl chain between the lactone ring and the THF rings.

NMR studies of formaldehyde acetal derivatives of annonaceous acetogenins that have diols in their aliphatic chains help determine relative stereochemistries of two stereogenic centers that evolve from the diols. Synthesis of per-Mosher ester derivatives of the acetals helps determine the absolute configurations of chiral positions that have other hydroxyl groups.

A new mono-THF acetogenin, gonionenin, which has a double bond in the aliphatic chain, is isolated from the bark of Goniothalamus giganteus. Mono-THF acetogenins are converted into bis-THF Annonaceous acetogenins with epoxidation and cyclization. The bis-THF compounds exhibit more bioactivities than the parent compounds. The facile reactions give high yields.

The absolute configuration of stereogenic carbinol centers in several annonaceous acetogenins was determined by 1H- and 19F-nuclear magnetic resonance analysis of Mosher ester derivatives. These acetogenins include five adjacent bis-tetrahydrofuran acetogenins (uvaricin, bullatacin, bullatacinone, asimicin and rolliniastatin 1) and four mono-tetrahydrofuran acetogenins (reticulatacin, isoannonacin-10-one, annonacin-10-one and annonacin). The configuration at the C(4) carbinol center in the acetogenins examined is R.

An acetogenin closely related to mucocin, the first tetrahydropyran (THP) ring-bearing acetogenin, that has an unsubstituted THP ring and an adjacent tetrahydrofuran ring (THF) has been isolated from Rollinia mucosa. Called muconin, it provides further proof of the existence of a new acetogenin type with THP ring(s) as the most significant structural characteristic. Mucoxin, the first acetogenin with a hydroxylated THF ring, is also reported. Muconin showed potent and selective in vitro cytotoxicities against pancreatic cancer and breast cancer (MCF-7) in a group of six human solid tumor cell lines. Mucoxin showed selective inhibition against MCF-7 in the same test run.

The research of the structure and bioactivity of mucocin indicates the first annonaceous acetogenin to bear a hydroxylated tetrahydropyran (THP) ring and a tetrahydrofuran (THF) ring. The NMR data reveal the trans configuration of the THF ring, and the presence of methylated alpha, beta-unsaturated gamma-lactone with a 4-OH. DEPT experiments reveals the existence of two methyl, ten methine and two quaternary carbons in acetogenin. The absolute stereochemistry of mucocin analyzed by the advanced Mosher ester methodology indicates absolute configurations are R, R and S at C-23, C-4 and C-36.