DESIGN, SYNTHESIS AND EVALUATION OF PROTEIN TYROSINE PHOSPHATASE 1B (PTP1B) INHIBITORY ACTIVITY OF HETEROCYCLIC DERIVATIVES OF CHALCONE SCAFFOLD

Abstract

Type 2 diabetes mellitus (T2DM) is considered one of the most common metabolic disorders which mainly associatewith consequences of hyperglycemia. Recently many macromolecular targets for diabetes have been invest igated and Protein tyrosine phosphatase 1B (PTP1B) is one such target for anti-diabetic medicinal agents. It is believed that inhibition of PTP1B offers anti-diabetic response by altering insulin resistance and signaling pathway. However agents possessing PTP1B inhibitory activity yet to come in market as anti-diabetic compounds therefore finding of such type of anti-diabetic agents is still in progress. Computational tools based on ligand and receptor interactions showed some prerequisite structural features for PTPIB inhibitory activity. In silico virtual screening was performed to design ligand with required structural features and on the basis of findings of virtual screening we designed some heterocyclic derivatives of chalcone scaffold. Designed ligands possess structural similarities with co-crystallized ligand bound with 3Dcrystal structure of PTP1B receptor. Therefore PTPIB inhibitory activity was expected with designed ligands. Moreover these ligands showed interactions with PTP1B receptor in molecular docking study, thus further synthesized and evaluated for their in-vitro PTPIB inhibitory activity using PTP1B enzyme colourimetric assay kit. Study observed 60.57 % inhibition of enzyme PTP1B when tested against compound AS-4 ((E)-3-(3-nitrophenyl)-1-(thiophen-2-yl) prop-2-en1-one) which was considered as most potent inhibitory agent.