Concise Synthesis of 1,1-Diarylvinyl Sulfones and Investigations on their Antiproliferative Activity via Tubulin Inhibition

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.

Keywords: Suzuki-Miyaura coupling; Tubulin polymerization inhibitor; antiproliferative activity; ceric ammonium nitrate; diarylethenes; vinyl sulfone.