title: Design, synthesis and biological evaluation of novel nitroaromatic compounds as potent glutathione reductase inhibitors.
abstract: Discovery of GR inhibitors has become very popular recently due to antimalarial and anticancer activities. In this study, the synthesis and GR inhibitory capacities of novel nitroaromatic compounds (NCs) (1-3) were reported. Some commercially available molecules were also tested for comparison reasons. The novel NCs were obtained in high yields using simple chemical procedures and exhibited much potent inhibitory activities against GR at low micromolar concentrations with K(i) values ranging from 0.211 to 4.57 μM as compared with well-known agents. Inhibition mechanism was assessed as being due to occlusion of the active site entrance by means of the NCs. Molecular docking results have shown that docking poses of ligands are able to construct binding interactions with the essential amino acids.
authors.affiliation: Batman University, Science and Art Faculty, Chemistry Department, Batman, Turkey.
authors.forename: Reşit
authors.initials: R
authors.lastname: Çakmak
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.forename: Deniz
authors.initials: D
authors.lastname: Ekinci
authors.forename: Murat
authors.initials: M
authors.lastname: Sentürk
authors.forename: Giray
authors.initials: G
authors.lastname: Topal
mesh_terms: D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D004136:Dinitrobenzenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004136:Dinitrobenzenes; D004791:Enzyme Inhibitors; D005980:Glutathione Reductase