Medicinal Chemistry Research

, Volume 27, Issue 2, pp 476–487 | Cite as

Exploring sulfonate esters of 5-arylidene thiazolidine-2,4-diones as PTP1B inhibitors with anti-hyperglycemic activity

  • Manoj Kumar Mahapatra
  • Rajnish Kumar
  • Manoj Kumar
Original Research
  • 113 Downloads

Abstract

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.

Keywords

PTP1B Diabetes Sulfonate ester 5-Arylidene-thiazolidine-2,4-dione Docking 

Notes

Acknowledgements

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.

Supplementary material

44_2017_2074_MOESM1_ESM.docx (3.8 mb)
Supplementary data

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Manoj Kumar Mahapatra
    • 1
  • Rajnish Kumar
    • 1
  • Manoj Kumar
    • 1
  1. 1.University Institute of Pharmaceutical Sciences, Panjab UniversityChandigarhIndia

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