Design and Synthesis of a Library of Thiazolidin-4-one Derivatives as Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors: An Attempt to Discover Novel Anti-diabetic Agents.

Design and Synthesis of a Library of Thiazolidin-4-one Derivatives as Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors: An Attempt to Discover Novel Anti-diabetic Agents. ChemMedChem. 2020 May 10;: Authors: Tripathi RKP, Patel AD, Pasha TY, Lunagaria P, Shah U, Bhambharoliya T Abstract Protein tyrosine phosphatase 1B (PTP1B) is an important target for treatment of diabetes. A series of thiazolidin-4-one derivatives 8-22 was designed, synthesized and investigated as PTP1B inhibitors. New molecules inhibited PTP1B with IC 50 in micromolar ranges. 5-(Furan-2-ylmethylene)-2-(4-nitrophenylimino)thiazolidin-4-one ( 17 ) exhibited maximum potency with competitive type of enzyme inhibition. SAR studies revealed various structural facets substantial for potency of these analogues. The findings revealed requirement of nitro group including hydrophobic heteroaryl ring for PTP1B inhibition. Molecular docking studies afforded good correlation between experimental and computational results. H-bonding and π-π interactions were responsible for optimal binding and effective stabilization of virtual protein-ligand complexes. Furthermore, in-silico pharmacokinetic properties of test compounds predicted their drug-like characteristics for potential oral use as anti-diabetic agents. Additionally, a binding site model demonstrating crucial pharmacophoric characteristics influencing potency and binding affinity of inhibitors has been proposed, which ca...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research