In this study, we synthesized a series of dihydropyrazole sulfonamide derivatives containing 2-hydroxyphenyl moiety as antitumor agents to target the matrix metalloproteinase-2 (MMP-2). All of the synthesized compounds were examined by bioactivity assays, in which compound 4c turned out as a potential antagonist of MMP-2 along with potent anticancer activity against four tumor cell lines. Structure-activity relationship analysis was also performed to examine how structural changes impacted the bioactivity. Suggested to be caused by the induction of apoptosis, the antitumor mechanism of 4c was further confirmed by PI combining with annexin V-FITC staining assay using flow cytometry analysis. These new findings along with molecular docking observations suggested that compound 4c could be developed as a potential anticancer agent.
Keywords: MMP-2; anticancer; dihydropyrazole sulfonamide; extracellular matrix enzyme; flow cytometry analysis.
© 2015 John Wiley & Sons A/S.