Design, synthesis, and biological evaluation of thiophene analogues of chalcones

Chalcones are characterized by possessing an enone moiety between two aromatic rings. A series of chalcone-like agents, in which the double bond of the enone system is embedded within a thiophene ring, were synthesized and evaluated for antiproliferative activity and inhibition of tubulin assembly and colchicine binding to tubulin. The replacement of the double bond with a thiophene maintains antiproliferative activity and therefore must not significantly alter the relative conformation of the two aryl rings. The synthesized compounds were found to inhibit the growth of several cancer cell lines at nanomolar to low micromolar concentrations. In general, all compounds having significant antiproliferative activity inhibited tubulin polymerization with an IC(50)<2microM. Several of these compounds caused K562 cells to arrest in the G2/M phase of the cell cycle.