Exploring sulfonate esters of 5-arylidene thiazolidine-2,4-diones as PTP1B inhibitors with anti-hyperglycemic activity
Protein tyrosine phosphatase 1B (PTP1B) has been identified as negative regulator of insulin and leptin signaling pathway, hence considered as a new therapeutic target of intervention for the treatment of type 2 diabetes. A series of eleven aryl/alkyl sulfonyloxy-5-arylidene thiazolidine-2,4-dione derivatives were synthesized and screened in vitro for PTP1B inhibitory activity and in vivo for anti-hyperglycemic activity. The introduction of aryl/alkyl sulfonate ester moiety was anticipated to yield PTP1B inhibitors with significant potency. Docking results revealed their bidentate nature of binding, and further helped in understanding the binding mode of ligands inside PTP1B enzyme. Compounds 13 and 14 were found to be potent PTP1B inhibitors with IC50 8.53 and 6.89 µM, respectively. Compounds 13, 14, and 18 have also shown significant lowering of blood glucose level as compared to pioglitazone.
KeywordsPTP1B Diabetes Sulfonate ester 5-Arylidene-thiazolidine-2,4-dione Docking
We gratefully acknowledge UGC (University Grant Commission), New Delhi, India for providing UGC-RFSMS fellowship to Manoj Kumar Mahapatra. We thank Mr. Avtar Singh (SAIF, Panjab University, Chandigarh, India) for doing the NMR study/characterization.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
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