title: Nitrophenyl derivatives as aldose reductase inhibitors.
abstract: Nitrophenyl derivatives were recently discovered as a new class of ALR2 inhibitors by means of docking and database screening of the National Cancer Institute database of organic molecules. The nitro group was predicted to bind to the Tyr48 and His110 active site residues of the enzyme, the site where acidic ALR2 inhibitors such as carboxylic acids bind in their anionic form. Given the novelty of these compounds, we decided to expand their structure-activity relationships by synthesizing and testing a series of derivatives and the corresponding compounds having a carboxylic group instead of the nitro moiety; the results obtained were rationalized by means of docking and molecular dynamics simulations. On the whole there is an agreement between inhibitory data and the results of molecular modeling experiments, supporting the hypothesized binding mode of these compounds.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Modena e Reggio Emilia, Via Campi 183, 41100 Modena, Italy. costantino.luca@unimo.it
authors.forename: Luca
authors.initials: L
authors.lastname: Costantino
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Ferrari
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gamberini
authors.forename: Giulio
authors.initials: G
authors.lastname: Rastelli
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001665:Binding Sites; D002264:Carboxylic Acids; D003198:Computer Simulation; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009596:Nitrophenols / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D009596:Nitrophenols; D000449:Aldehyde Reductase