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.