Microtubules are among the most successful targets of compds. potentially useful for cancer therapy. A new series of inhibitors of tubulin polymn. based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)-4,5,6,7-tetrahydrothieno[b]pyridine mol. skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymn., and cell cycle effects. The most promising compd. in this series was 2-amino-3-(3,4,5-trimethoxybenzoyl)-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[b]pyridine (I), which inhibits cancer cell growth with IC50-values ranging from 25 to 90 nM against a panel of four cancer cell lines, and interacts strongly with tubulin by binding to the colchicine site. In this series of N6-carbamate derivs., any further increase in the length and in the size of the alkyl chain resulted in reduced activity.
Synthesis and Biological Evaluation of 2-Amino-3-(3’,4’,5’-Trimethoxybenzoyl)-6-Substituted-4,5,6,7-Tetrahydrothieno[2,3-c]pyridine Derivatives as Antimitotic Agents and Inhibitors of Tubulin Polymerization
ROMAGNOLI, Romeo;BARALDI, Pier Giovanni;
2008
Abstract
Microtubules are among the most successful targets of compds. potentially useful for cancer therapy. A new series of inhibitors of tubulin polymn. based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)-4,5,6,7-tetrahydrothieno[b]pyridine mol. skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymn., and cell cycle effects. The most promising compd. in this series was 2-amino-3-(3,4,5-trimethoxybenzoyl)-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[b]pyridine (I), which inhibits cancer cell growth with IC50-values ranging from 25 to 90 nM against a panel of four cancer cell lines, and interacts strongly with tubulin by binding to the colchicine site. In this series of N6-carbamate derivs., any further increase in the length and in the size of the alkyl chain resulted in reduced activity.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.