Background: Protein Tyrosine Phosphatase 1B (PTP1B) is an attractive target for antidiabetic
drug discovery owing to its pivotal role as a negative regulator of insulin and leptin signaling.
Objective: The objective of this research is to design, synthesize, and evaluate some acetamidobenzoic
acid derivatives as a novel class of protein tyrosine phosphatase 1B inhibitors with therapeutic
potential for Type II diabetes.
Methods: 3-(2-(Benzo[d]thiazol-2-ylthio)acetamido)benzoic acid derivatives 4(a-j) were synthesized
and characterized by employing spectral studies. All the synthesized compounds were
screened for in vitro PTP1B inhibitory activity and the most potent compound in the series was also
evaluated for in vivo anti-hyperglycemic activity using STZ induced diabetic Wistar rat model. Molecular
docking studies were also performed with the most potent analog using FlexX docking algorithm
to delineate its binding mode to the active site of the PTP1B.
Results: Among all the synthesized compounds, 3-(2-(benzo[d]thiazol-2-ylthio)acetamido)-4-
methylbenzoic acid (4f) displayed good PTP1B inhibitory activity with an IC50 value of 11.17 μM.
The compound also exhibited good anti hyperglycemic efficacy in streptozotocin induced diabetic
Wistar rats. Docking studies with 4f revealed that the compound bound in the catalytic and second
aryl binding site of the PTP1B.
Conclusion: Overall, compound 4f with good in vitro PTP1B inhibitory potency and in vivo antihyperglycemic
efficacy would be a valuable lead molecule for the development of acetamidobenzoic
acid based PTP1B inhibitors with antidiabetic potential.