title: Synthesis and SAR study of 4,5-diaryl-1H-imidazole-2(3H)-thione derivatives, as potent 15-lipoxygenase inhibitors.
abstract: A series of 4,5-diaryl-1H-imidazole-2(3H)-thione was synthesized and their inhibitory potency against soybean 15-lipoxygenase and free radical scavenging activities were determined. Compound 11 showed the best IC(50) for 15-LOX inhibition (IC(50) = 4.7 μM) and free radical scavenging activity (IC(50) = 14 μM). Methylation of SH at C(2) position of imidazole has dramatically decreased the 15-LOX inhibition and radical scavenging activity as it can be observed in the inactive compound 14 (IC(50) >250 μM). Structure activity similarity (SAS) showed that the most important chemical modification in this series was methylation of SH group and Docking studies revealed a proper orientation for SH group towards Fe core of the 15-LOX active site. Therefore it was concluded that iron chelating could be a possible mechanism for enzyme inhibition in this series of compounds.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Assadieskandar
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.forename: Marjan
authors.initials: M
authors.lastname: Salehi
authors.forename: Hamid
authors.initials: H
authors.lastname: Sadeghian
authors.forename: Maliheh
authors.initials: M
authors.lastname: Alimardani
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sakhteman
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D015195:Drug Design; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D016859:Lipoxygenase Inhibitors