SYNTHESIS AND PTP1B INHIBITORY ACTIVITY OF NOVEL BENZOTHIAZOLE AND 1, 2, 4-TRIAZOLE LINKED ACETAMIDO BENZOIC ACID DERIVATIVES AS ANTIDIABETIC ACTIVITY

Abstract

The present research reports the synthesis and PTP1B inhibitory activity evaluation of a series of substituted benzthiazole/ 1, 2, 4-triazole linked acetamido benzoic acid derivatives designed based on a lead molecule, 4-methyl-3- (2-(5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-ylthio) acetamido) benzoic acid identified previously in our laboratory. All the synthesized derivatives showed improved PTP1B inhibitory activity, out of which, compound 6c (4- methyl-3-(2-(5-(pyridin-4-yl)-4H-1, 2, 4-triazol-3ylthio) acetamido) benzoic acid) elicited potent PTP1B inhibitory activity with IC50 value 6.45 μM. Furthermore, compound 6c also showed good in vivo antidiabetic activity in streptozotocin-induced diabetes model. Molecular docking studies performed with 6c revealed the binding mechanism of the molecule in the catalytic site of PTP1B. These results demonstrate that compound 6c might serve as a valuable lead molecule for the development of promising antidiabetic agents targeting PTP1B.