Arylcinnamido-propionone conjugates as tubulin polymerization inhibitors and apoptotic inducers

Abstract

A series of cinnamido-propionone conjugates (4–6a-h and 7a-f) has been designed, synthesized and evaluated for their anticancer potential against some human cancer cell lines. Among them, conjugates 6d and 6g have shown significant cytotoxic activity against prostate cancer cells (DU-145) displaying IC50 of 7.48 and 8.91 μM respectively. Studies to understand the mechanism of action of 6d and 6g indicate that they inhibit the tubulin polymerization thereby arresting the cell cycle in G2/M phase. Furthermore, studies such as mitochondrial membrane potential and Annexin V-FITC assay suggested that these conjugates 6d and 6g induced cell death by apoptosis. The molecular docking studies suggested that the binding by these conjugates takes place at the colchicine site of the tubulin protein. Keywords: Cinnamides, Cytotoxicity, Tubulin polymerization inhibitors, Apoptosis