Cytotoxic lignans from fruits of Cleistanthus tonkinensis.

Seven new lignans, cleistonkinins A- E (1-5), cleistonkisides A and B (6-7) were isolated from the fruits of Cleistanthus tonkinensis (Euphorbiaceae), together with five known aryltetralin lignans, cleisindoside B (8), cleistantoxin (9), cleisindoside D (10), neocleistantoxin (11) and polygamain (12). Their structures were established from spectral analysis, including mass spectrometry and 2D-NMR. The absolute configurations of 4-7 were determined by analysis of their experimental CD spectra and comparison with calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 6 had selective inhibition with moderate cytotoxicity against Pan C1 and A549 cell lines, respectively. Cleistantoxin (9) was significantly active against A549, HeLa, Hep3B, Pan C1 and MCF7 cell lines while it was less cytotoxic against HeLa cells. Neocleistantoxin (11) exhibited remarkable inhibition toward A549, HeLa, MCF7 and Pan C1. This is the first report for cytotoxicity of 9 and 11 against A549, Hep3B and Pan C1 cell lines.

Synthesis and biological evaluation of oseltamivir analogues from shikimic acid.

New oseltamivir analogues were designed and synthesized, starting from shikimic acid. Biological evaluation against three human cancer cell lines (KB, MCF7 and Lu-1) showed that many of them exhibited cytotoxic activity. Azides 5 are more active than the corresponding amines 6. Thus, the reduction of the azide group into amine led to the loss of cytotoxicity. The compounds with a cyclohexanemethyloxy group at C-3 were more active than the other investigated compounds belonging to the same series. This cyclohexanemethyloxy group seems to be critical for the cytotoxic activity of this class of compounds. The synthetic oseltamivir analogues 6a-e had no inhibition activity, even at the concentration of 50 microM when they were evaluated for their in vitro influenza A neuraminidase inhibitory activity by an enzymatic assay.

Synthesis and biological evaluation of febrifugine analogues.

A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.