title: Design of benzene-1,2-diamines as selective inducible nitric oxide synthase inhibitors: a combined de novo design and docking analysis.
abstract: Selective inhibition of inducible nitric oxide synthases (iNOS) has been a challenging problem for researchers pursuing work in finding methods to treat inflammatory disorders, shock, etc. Though many inhibitors have been studied to date, all are associated with selectivity or potency problems. Additionally, most of the reported compounds have several similarities and fewer number of novel structures are being tried. There is an increasing need to design novel molecules for this target. In this work, de novo design using LUDI, combined with docking analysis using FlexX has been employed in an attempt to identify novel scaffolds. Benzene-1,2-diamines were identified which could mimic the interactions of the substrate analogs and other inhibitors. Comparative docking scores in each of the isoforms of nitric oxide synthase were employed to recognize hits for iNOS selectivity.
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, 160 062 Punjab, India.
authors.forename: Sandrea M
authors.initials: SM
authors.lastname: Francis
authors.forename: Amit
authors.initials: A
authors.lastname: Mittal
authors.forename: Manishika
authors.initials: M
authors.lastname: Sharma
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Bharatam
mesh_terms: D003959:Diamines / Q000737:chemistry*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008024:Ligands; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments
chemical_list: D003959:Diamines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008024:Ligands; D010446:Peptide Fragments; D052247:Nitric Oxide Synthase Type II