Synthesis and biological evaluation of combretastatin-amidobenzothiazole conjugates as potential anticancer agents

A series of combretastatin-amidobenzothiazole conjugates have been synthesized and evaluated for their anticancer activity. All these compounds exhibited significant anticancer activity and the most potent compound (11a) showed GI50 values ranging 0.019–11 μM. Biological studies such as cell cycle distribution, effect on tubulin polymerization and effect on ERK signalling pathway have been examined in MCF-7 cell line. FACS analysis revealed that these compounds induced cell cycle arrest at G2/M phase. Compound 11a showed significant effect on tubulin polymerization and affected the ERK signalling pathway that result in the decreased levels of ERK1/2, p-ERK and c-Jun proteins. Docking experiments have shown that the active molecules interact and bind well in the ATP binding pocket of ERK protein.

A series of combretastatin-amidobenzothiazole conjugates have been synthesized and evaluated for their anticancer activity.Figure optionsDownload as PowerPoint slideHighlights
► New series of combretastatin-amidibenzothiazole conjugates have been synthesized.
► These conjugates were evaluated for their anticancer activity.
► These compounds showed cell cycle arrest at G2/M phase.
► The active compounds showed effect on tubulin, c-Jun and ERK protein levels.
► The ERK inhibition exhibited by active compounds rationalized by molecular modeling studies.