1,2-Benzisoxazole-3-acetamide derivatives as dual agents for DPP-IV inhibition and anticancer activity

Herein, we have designed various benzisoxazole acetamide derivatives with and without glycine spacer as DPP-IV inhibitors. Compounds 9a-d and 11a-e were synthesized and screened for their in vitro DPP-IV inhibition. Compounds 11a and 11c showed moderate activity for DPP-IV inhibition, whereas other remained inactive at 25-200 mu M concentrations. DPP-IV inhibition can be a good strategy for modulating diabetes and cancer; hence, we have screened compounds 9a-d and 11a-e for their anticancer activity using MTT assay against A549 and MCF7 cell lines. Compounds 9a-d without glycine spacer have shown good anticancer activity compared to compounds 11a-e with glycine spacer. Compound 9b has shown moderate activity with IC50 values 4.72 +/- 0.72 and 4.39 +/- 0.809 mu M against A549 and MCF7 cell lines, respectively. Interestingly, compound 9c with cyano group has shown very good anticancer activity with IC50 2.36 +/- 0.34 mu M against MCF7 cell line as compared to fluorouracil with IC50 45.04 +/- 1.02 mu M. [GRAPHICS] .