title: Synthesis, biological evaluation and in silico studies of 5-(3-methoxybenzylidene)thiazolidine-2,4-dione analogues as PTP1B inhibitors.
abstract: PTP1B (protein tyrosine phosphatase 1B) dephosphorylates the insulin receptor substrate and thus acts as a negative regulator of the insulin and leptin signalling pathway. Recently, it has been considered as a new therapeutic target of intervention for the treatment of type2 diabetes. A series of aryl/alkylsulfonyloxy-5-(3-methoxybenzylidene)thiazolidine-2,4-dione derivatives were synthesized, screened in vitro for their PTP1B inhibitory activity and in vivo for anti-hyperglycaemic activity. Docking results further helped in understanding the nature of interactions governing the binding mode of ligands inside the active site of PTP1B. Among the synthesized compounds, 13 and 16 were found to be potent PTP1B inhibitors having IC50of 7.31 and 8.73μM respectively. Significant lowering of blood glucose level was observed in some of the synthesized compounds in in vivo study.
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Mahapatra
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Rajnish
authors.initials: R
authors.lastname: Kumar
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. Electronic address: manoj_uips@pu.ac.in.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000201:enzymology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000201:enzymology; D051379:Mice; D062105:Molecular Docking Simulation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D004791:Enzyme Inhibitors; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: 5-(3-Methoxybenzylidene)-thiazolidine-2,4-dione; Diabetes; Docking; PTP1B