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 of 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 iodosulfonylation-Suzuki coupling sequence. Results: As hypothesized, these compounds showed good anti-proliferative activity against different tissue-specific cancer cell lines: MCF-7, DU-145, A-549, HepG2, and HeLa. The most active compound, p-nitrophenyl 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.

A formal vinylic substitution reaction for the synthesis of α,β-unsaturated enol esters and their anticancer potential

“…2 Our interest in sulfone chemistry arose partly due to the well-appreciated, favourable influence of arylsulfonyl groups on the anticancer activities of molecules bearing them. 3 The unique chemical virtues of arylsulfonyl groups 4 were also crucial in the development of a ‘formal vinylic substitution reaction’ that amounts to an overall substitution of a vinylic bromide on a bromoallyl sulfone. 5 We surmised that the approach could be tailored for preparing sulfone-group bearing cinnamoyl enol esters.…”

Synthesis and characterization of novel combretastatin analogues of 1,1-diaryl vinyl sulfones, with antiproliferative potential via in-silico and in-vitro studies

“…1 f). Many strategies have been used to develop several synthetic analogues of combretastatin A-4 32 – 37 , and in this study a new class of CA-4, 1,1-diaryl vinyl sulfones, have been designed, docked with beta-tubulin (colchicine site) to investigate its likely interaction as well as pharmacokinetic property predictions. The compounds were synthesized and tested in-vitro against four human cancer cell lines: MDA-MB 231(breast cancer), HeLa (cervical cancer), A549 (lung cancer), and IMR-32 (neuroblast cancer), along with a normal cell line HEK-293 (human embryonic kidney cell) by employing 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay to access their cytotoxicity and antiproliferative properties, and expressed as IC 50 (µM) values.…”