Cytotoxicity of Rhamnosylanthraquinones and Rhamnosylanthrones from Rhamnus nepalensis.

An extract of the fruits of Rhamnus nepalensis collected in Hoa Binh Province, Vietnam, was cytotoxic to KB cells. A bioassay-guided fractionation led to the isolation of a series of known anthraquinones and anthrones, one new rhamnosylanthraquinone, 3'-O-acetylfrangulin A (8), several new rhamnosylanthrones, the prinoidin-emodin bianthrones (9A-D), the prinoidin bianthrones (10A,B), and the rhamnepalins (11A-C). A structure-cytotoxic activity relationship study was performed on these isolates and some semisynthetic derivatives.

Semisynthesis of D-ring modified taxoids: novel thia derivatives of docetaxel.

Two novel 5(20)-thia analogues of docetaxel have been synthesized from 10-deacetylbaccatin III or taxine B and isotaxine B. The key step of these syntheses is the concomitant thietane ring formation and acetylation of the tertiary alcohol at C-4. Both compounds are less cytotoxic than docetaxel but have divergent activity on microtubule disassembly.

Neutral and basic taxoid contents in the needles of Taxus species.

The concentrations of paclitaxel, 10-deacetylbaccatin III (10-DAB III), basic taxoids (= "total alkaloids", TA), taxine B and isotaxine B (= "taxines B", TBS) in the dried needles of 127 trees belonging to 30 Taxus cultivars and species were determined by HPLC. Neutral and basic taxoid contents varied in individual trees within species as well as among varieties and species. The objective of this large analysis was to select the highest-yielding trees for each metabolite.

Structure-activity relationship of polyisoprenyl benzophenones from Garcinia pyrifera on the tubulin/microtubule system.

Microtubule disassembly inhibitory properties have been established for the known polyisoprenylated benzophenones xanthochymol (1a) and guttiferone E (1b). The compounds were isolated from the fruits of Garcinia pyrifera collected in Malaysia. A structure-activity relationship study, including natural and semisynthetic derivatives, delineated some structural features necessary for the interaction with tubulin within this compound class.

[Chemical and biological studies on Taxol (Paclitaxel) and Taxotere (Docetaxel), new antineoplastic agents]. / Recherches chimique et biologique autour du Taxol (Paclitaxel) et du Taxotère (Docetaxel), nouveaux agents antitumoraux.

Since the discovery of Taxol and of its antitumor activity a number of chemical, pharmacological and clinical studies have been performed on this natural diterpene isolated from the genus Taxus. Because the extraction of Taxol from the bark is expensive, difficult and damaging to the Taxus species, alternative sources have been studied. To date, one of the most promising alternatives is the semisynthesis of Taxol from 10-deacetylbaccatin III, a renewable precursor found in the needles of the European yew tree, Taxus baccata. From this natural compound, a number of new active compounds bearing different substituents at carbons 2, 4, 5, 7, 10, 13, 2' and 3' have been prepared. Among the new substances, Taxotere (N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol) was found to be one of the most potent in its interaction to the cellular target of antitumor taxoids: tubulin. The chemistry and structure-activity relationships of the antitumor taxoids are presented.

[Anticancer substances of vegetable origin. Spindle poisons: vincaleukoblastine, leurocristine and navelbine; taxol and taxotere]. / Substances anticancéreuses d'origine végétale. Les poisons du fuseau: vincaleucoblastine, leurocristine et Navelbine; taxol et Taxotère.

The biological activity of spindle poisons can easily be measured using an in vitro assay based on the interaction of these substances with their cellular "receptor": tubulin. The use of this assay led us to select Navelbine and Taxotere as antimitotic substances. These compounds, as well as their natural parents: vincaleucoblastine, leurocristine and taxol respectively, have been obtained by semi-synthesis using relatively abundant natural precursors as starting materials. This paper summarizes the preparation of these important anticancer drugs.

Alkaloids of Androcymbium melanthioides var. stricta1.

The aerial parts of ANDROCYMBIUM MELANTHIOIDES yielded known alkaloids cornigerine, colchicine, N-formyl- N-deacetylcolchicine, 2-demethylcolchicine, 3-demethylcolchicine, demecolcine, 2-demethyldemecolcine, 3-demethyldemecolcine, beta-lumicornigerine, beta-lumicolchicine, gamma-lumicolchicine, androcymbine, O-methylandrocymbine, and melanthioidine. Of these, O-methylandrocymbine and beta-lumicornigerine are reported for the first, time. The alkaloid, formerly designated as compound AM-3, has been identified as N-deacetyl- N-dimethyl-gamma-lumicornigerine 1. Its spectral data are given.

Structure--antitubulin activity relationship in steganacin congeners and analogues. Inhibition of tubulin polymerization in vitro by (+/-)-isodeoxypodophyllotoxin.

A new series of 23 synthetic analogues of the naturally occurring antitumor lignan steganacin was tested for the inhibition of microtubule assembly in vitro. Interestingly, (+/-)-isopicrostegane (I50 = 5 microM) was found to be almost as active as (+/-)-steganacin(I50 = 3.5 microM). On the other hand, racemic isodeoxypodophyllotoxin has an inhibiting activity of microtubule assembly comparable to that of (-)-podophyllotoxin, whereas (-)-isodeoxypodophyllotoxin is totally inactive.