Thitima Pengsuparp

Lycorine alkaloids from Hymenocallis littoralis

From Hymenocallis littoralis, one new alkaloid, named littoraline, together with 13 known lycorine alkaloids and one lignan, were isolated. The structure and NMR assignments of this new alkaloid were determined by 1D and 2D NMR techniques. Littoraline showed inhibitory activity of HIV reverse transcriptase, and lycorine and haemanthamine showed potent in vitro cytotoxicity.

Phenolic constituents of the liverwort: Four novel cyclic bisbibenzyl dimers from Blasia pusilla L

Abstract Four novel, cyclic, bisbibenzyl dimers (pusilatins A-D), six bibenzyl derivatives, apigenin 7-O-β- d -glucoside , shikimic acid and five orsellinic acid derivatives have been isolated from the methanolic extract of the liverwort Blasia pusilla L. and their structures characterized by a combination of spectral data, chemical modification and X-ray crystallographic analysis. The previously assigned structure of pusilatin D was revised. Pusilatins B and C showed DNA polymerase β inhibitory activity.

Four diterpene esters from Euphorbia myrsinites.

The Turkish species Euphorbia myrsinites has yielded four new tetracyclic diterpene tetraesters from a cytotoxic acetone extract, in addition to the known cycloartane-type triterpenoids and betulin. The new compounds and their hydrolysis product have been extensively characterized by high field spectroscopic techniques, and were shown to be four new tetraesters of the parent alcohol, myrsinol.

Evaluation of the cytotoxic mechanism mediated by baccatin III, the synthetic precursor of taxol.

Baccatin III, which is used as a precursor for the semisynthesis of taxol, showed cytotoxic activity against a variety of cancer cell lines in culture, with ED50 values ranging from approximately 8 to 50 microM. Although the potency of this response is much lower than that mediated by taxol, it was interesting to note that any significant cytotoxic response could be mediated by this compound. Thus, it was considered of potential value to investigate the mechanism of cytotoxic action. Consistent with an antimitotic mode of action, baccatin III induced cultured cells to accumulate in the G2 + M phases of the cell cycle. However, unlike taxol, which potentiates the polymerization of tubulin, baccatin III mediated an antimitotic response through inhibition of the polymerization reaction, similar to colchicine, podophyllotoxin, or vinblastine. Accordingly, baccatin III was unable to reduce the extent of Ca(2+)-induced depolymerization, a hallmark of the biological response mediated by taxol. To further explore the mode of antimitotic activity facilitated by baccatin III, competitive interactions with the colchicine, podophyllotoxin, and vinblastine binding sites of tubulin were investigated. Baccatin III displaced the binding of radiolabeled colchicine or radiolabeled podophyllotoxin, but did not displaced the binding of radiolabeled vinblastine. Greater affinity with the colchicine binding site was observed and the kinetics of inhibition were shown to be mixed. The side chain of taxol, which differentiates the molecule from baccatin III and is known to be of requisite importance for the unique activity mediated by taxol, is not by itself active in any of these processes. Thus, the baccatin III nucleus of taxol may lead to an interaction with tubulin through traditional binding sites. Facilitated by this interaction, the intact molecule of taxol may thereby be permitted to potentiate tubulin polymerization and block cells in the mitotic phase of the cell cycle.