Ligand Based Designing, Synthesis and PTP1B Inhibitory Activity of Some Chalcone Derivatives

Abstract

Inhibition of enzyme is considered one of the rationale approaches to treat many diseases and Protein tyrosine phosphatase 1B (PTP1B) is one such type of target for the treatment of diabetes. It is believed that inhibition of PTP1B alters insulin resistance thus imparts therapeutic benefits in Type 2 diabetes mellitus (T2DM). Computer aided approaches of drug design and virtual modeling described some structural features must be present in PTPIB inhibitory agent. Considering this we designed and synthesized some chalcones and their heterocyclic derivatives as PTP1B inhibitors. Designed ligands were evaluated for their ability to interacts with 3D crystal structure of PTP1B enzyme using molecular docking study; compounds AJ-9 ((E)-3-(3,4-dimethoxyphenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one) and AJ-10 ((E)-3-(furan-2-yl)-1-(4-hydroxyphenyl)prop-2-en-1-one) exhibited desired interactions with PTP1B receptor in molecular docking study. Furthermore synthesized compounds were also tested for their enzyme (PTP1B) inhibitory activity using in-vitro colourimetric assay kit. Compound AJ-10 was observed as most potent enzyme inhibitor with 62.87 % inhibition of PTP1B during in-vitro assay. Study suggested prominent anti-hyperglycemic potential of tested compounds.