Design, synthesis and molecular modelling studies of novel 3-acetamido-4-methyl benzoic acid derivatives as inhibitors of protein tyrosine phosphatase 1B

2013 ◽  
Vol 70 ◽  
pp. 469-476 ◽  
Author(s):  
Monika Rakse ◽  
Chandrabose Karthikeyan ◽  
Girdhar Singh Deora ◽  
N.S.H.N. Moorthy ◽  
Vandana Rathore ◽  
...  
Keyword(s):  
Benzoic Acid ◽  
Molecular Modelling ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Design Synthesis ◽  
Protein Tyrosine ◽  
Benzoic Acid Derivatives ◽  
Molecular Modelling Studies ◽  
Modelling Studies

Design, synthesis and biological evaluation of 3-(2-(benzo[d]thiazol-2- ylthio)acetamido)benzoic acid derivatives as inhibitors of protein tyrosine phosphatase 1B

2020 ◽  
Vol 17 ◽  
Author(s):  
Monika Rakse ◽  
Chandrabose Karthikeyan ◽  
Narayana Subbiah Hari Narayana Moorthy ◽  
Ram Kishore Agrawal
Keyword(s):  
Benzoic Acid ◽  
Protein Tyrosine Phosphatase ◽  
Inhibitory Activity ◽  
Tyrosine Phosphatase ◽  
Docking Studies ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Benzoic Acid Derivatives

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 acetamido benzoic 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 and Discussion: 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 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 acetamido benzoic acid based PTP1B inhibitors with antidiabetic potential.

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