ChemInform Abstract: Antitumor Agents. Part 183. Syntheses, Conformational Analyses, and Antitubulin Activity of Allothiocolchicinoids.

Abstract

are prepared from compound (III) via optical resolution of the corresponding camphanates followed by hydrolysis and acylation reactions. Key intermediate (II) is derived from known thiocolchicone (I) by ring contraction. With exception of (-)-(IVc) all compounds show strong inhibitory effects on the tubulin polymerization reaction. Compounds (II) and (-)-(IVa) also exhibit potent antitumor activity against most cell lines in NCI's in vitro screening. -(SHI, Q.; CHEN, K.; CHEN, X.; BROSSI, A.; VERDIER-PINARD, P.; HAMEL, E.; MCPHAIL, A. T.; TROPSHA, A.; LEE, K.-H.; J.

Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives

“…The simplest option to modify the substitution pattern of colchicine ring C is the replacement of the tropolone methoxy group by reaction with a sulfur nucleophile, as in the synthesis of thiocolchicine (6). 152 The conversion of 1 into isocolchicine (192) 153 involves a swap of the two oxygen functionalities (Scheme 24).…”

“…However, colchicide (193) was found to exhibit an in vitro activity comparable to colchicine, with 87% protein binding at a concentration of 25 μM (90% for colchicine Scheme 24. Synthesis of Thiocolchicine (6), 152 Isocolchicine (192), 153 under the same conditions). 158 Moreover, compared to colchicine (1), colchicide (193) proved to be at least 30 times less toxic after a single intramuscular injection.…”