Antineoplastic agents. 147. Isolation and structure of the powerful cell growth inhibitor cephalostatin 1

ESI‐QqTOF‐MS/MS and APCI‐IT‐MS/MS analysis of steroid saponins from the rhizomes of Dioscorea panthaica

“…In vitro assays showed that OSW-1 was extremely toxic against a broad spectrum of malignant tumor cells, such as leukemia HL-60, mouse mastrocarcinoma, human pulmonary adenocarcinoma, human pulmonary large cell carcinoma, and human pulmonary squamous cell carcinoma including adriamycin-resistant P388 leukemia and camptothecin-resistant P388, with IC50 between 0.1 and 0.7 nM, which is about 10-100 times more potent than those of the clinically applied anticancer agents, such as mitomycin C, adriamycin, cisplatin, camptothecin and taxol. 65 The cytotoxicity profile of OSW-1 is strikingly similar to that of cephalostatins, a group of dimeric steroidpyrazines from marine organisms, 67 with Pearson correlation coefficients between 0.60 and 0.83, 65 while structurally, the aglycone of OSW-1 is reminiscent of half of the cephalostatins. Fuchs therefore hypothesized that they might have the same mechanism of action.…”

Enantioselective Synthesis of (+)-Cephalostatin 1

“…4 The average GI 50 of 1 against the NCI-60, a collection of 60 human cancer cell lines, is 1.8 nM. 5 Three other molecules, ritterazine B (2), 6 OSW-1 (3) 7 and schweinfurthin A (4) 8 have cytotoxicity patterns resembling 1, suggesting that all three compounds share similar mechanisms.…”

Recherche de substances naturelles à activité thérapeutique (2)

“…Stimulé par la forte activité antitumorale des extraits de cet organisme, G.R. Pettit parvient, en 1988, à purifier et à identifier la première molécule active, la céphalostatine 1 (Figure 6), dont la structure sera déterminée après cristallisation [28]. La céphalos-tatine 1 est le premier membre d'une famille de 19 céphalostatines.…”