Structure–Activity Relationships of UTX-121 Derivatives for the Development of Novel Matrix Metalloproteinase-2/9 Inhibitors

Celecoxib, a nonsteroidal anti-inflammatory drug, has been reported to have antitumor and antimetastatic activities, it potential for application in cancer treatments. The expression of matrix metalloproteinase (MMP)-2/9 is strongly correlated with malignancy, inhibition these MMPs believed be effective improving the effects drugs. We previously revealed that UTX-121, which converted sulfonamide celecoxib methyl ester, more potent MMP-2/9 inhibitory activity than celecoxib. Based on findings, we identified compounds improved MMP through structure–activity relationship (SAR) study, using UTX-121 as lead compound. Among them, 9c 10c, group p-tolyl was substituted Cl or F, showed significantly higher suppressed activation pro MMP-2. Our findings suggest 10c may development drugs targeting MMP.