Design, synthesis, evaluation and 3D-QSAR analysis of benzosulfonamide benzenesulfonates as potent and selective inhibitors of MMP-2

Abstract

A novel series of MMPIs was designed, synthesized and purified using a scaffold modification strategy. The new compounds were also evaluated for biological activity against A549, MCF-7, HepG2 and Hela as potential inhibitors of MMP-2. The most potent inhibitor against MMP-2 was compound 19 (IC₅₀ = 0.38 μM). Its antitumor effect is believed to be due to the induction of apoptosis, which is further confirmed by Annexin V-FITC/PI staining assay using flow cytometry analysis. Furthermore, all the compounds were evaluated for cytotoxicity against 293T. In addition, 3D-QSAR studies were conducted. The result showed that the benzosulfonamide benzenesulfonate MMPIs may prove interesting lead candidates to target MMP-2 associated tumor, where the MMP-2 domain is located extracellularly.