title: X-ray and molecular modelling in fragment-based design of three small quinoline scaffolds for HIV integrase inhibitors.
abstract: Crystal structures of three small molecular scaffolds based on quinoline, 2-methylquinoline-5,8-dione, 5-hydroxy-quinaldine-6-carboxylic acid and 8-hydroxy-quinaldine-7-carboxylic acid, were characterised. 5-Hydroxy-quinaldine-6-carboxylic acid was co-crystallized with cobalt(II) chloride to form a model of divalent metal cation-ligand interactions for potential HIV integrase inhibitors. Molecular docking into active site of HIV IN was also performed on 1WKN PDB file. Selected ligand-protein interactions have been found specific for active compounds. Studied structures can be used as scaffolds in fragment-based design of new potent drugs.
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Kraków, Poland. majerz.maniecka@gmail.com
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Majerz-Maniecka
authors.forename: Robert
authors.initials: R
authors.lastname: Musiol
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Skórska-Stania
authors.forename: Dominik
authors.initials: D
authors.lastname: Tabak
authors.forename: Pawel
authors.initials: P
authors.lastname: Mazur
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Oleksyn
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Polanski
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D019428:HIV Integrase Inhibitors; D008024:Ligands; D011804:Quinolines; C037219:quinoline; D019427:HIV Integrase