ABSTRACT
BACKGROUND: Discovery of small molecules that inhibit tubulin polymerization is an attractive strategy for the development of new and improved anti-proliferative agents. OBJECTIVE: A series of novel 2-sulfonyl-1,1-diarylethenes were designed towards this end keeping in view the favorable chemical and pharmacological virtues of unsaturated sulfones. METHODS: Rapid, convenient and efficient two-step assembly of the designed molecules was achieved by the vicinal iodo-sulfonylation-Suzuki coupling sequence. RESULTS: As hypothesized, these compounds showed good anti-proliferative activity against different tissuespecific cancer cell lines: MCF-7, DU-145, A-549, HepG2, and HeLa. The most active compound, pnitrophenyl ring-bearing analog, exhibited an IC50 value of 0.90µM against A-549 cells. Flow cytometry studies on this derivative revealed that it arrests the cell cycle of A-549 cells at the G2/M phase. This compound exhibited molecular binding to tubulin as well as tubulin polymerization inhibition comparable to that of colchicine. CONCLUSION: A new class of potent, tubulin binding anticancer agents based on 1,1,-diarylvinyl sulfone scaffold has been designed and synthesized.
