title: Comparative molecular similarity indices analysis (CoMSIA) studies of 1,2-naphthoquinone derivatives as PTP1B inhibitors.
abstract: Protein tyrosine phosphatase-1B (PTP1B) has been demonstrated to play a key role in the negative signalling pathway of insulin. Potent and orally active PTP1B inhibitors are considered to be promising pharmacological agents for the treatment of type-2 diabetes and resistance to weight gain. CoMSIA studies have been preformed on 1,2-naphthoquinone derivatives that are reported to be potential non-peptidic inhibitors of PTP1B. For the selection of dataset to develop the model, the reported molecules were subjected to property filters and segregated into training and test set. As the crystal structure of PTP1B-naphthoquinone derivative is not known, the most active molecule was subjected to simulated annealing dynamics method and the lowest energy conformer was reminimised and considered as the bioactive conformation. Database-inertial alignment was followed for aligning the molecules. Different CoMSIA models were built to get the best related field.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar (Mohali) 160 062, India. mesophia@niper.ac.in
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sobhia
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Bharatam
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry* / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D009285:Naphthoquinones; C040756:1,2-naphthoquinone; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases