Design of Novel Biphenyl-2-thioxothiazolidin-4-one Derivatives as Potential Protein Tyrosine Phosphatase (PTP)-1B Inhibitors Using Molecular Docking Study

Abstract

Protein Tyrosine Phosphatase (PTP)-1B is a cytosolic receptor like PTPase, which plays an important role in treatment of type 2 diabetes mellitus (T2DM) via negative regulation of insulin signaling pathway. It is evident from the literature that biphenyl ring substituted compounds possess significant PTP-1B inhibitory activity due to extended interaction of the additional phenyl ring with the allosteric site of PTP-1B along with sufficient lipophilicity to cross intracellular barrier. Additionally, 2-thioxothiazolidin-4-one scaffold is a bio-isostere of 2, 4-thiazolidinedione with potent antidiabetic potential. Therefore, it was considered of interest to design and study the mode of binding of novel N- 3 substituted biphenyl-2-thioxothiazolidin-4-one derivatives using molecular docking technique by MVD software. The results of our designing study may be useful for the future development of novel PTP-1B inhibitors for the management of T2DM. Keywords: Biphenyl, insulin signaling pathway, molecular docking, PTP-1B, T2DM, 2-Thioxothiazolidin-4-one.