title: Synthesis, biological evaluation and docking study of 3-aroyl-1-(4-sulfamoylphenyl)thiourea derivatives as 15-lipoxygenase inhibitors.
abstract: A series of 3-aroyl-1-(4-sulfamoylphenyl)thiourea derivatives containing sulfonamide moiety were designed and synthesized as 15-lipoxygenase (15-LOX) inhibitors. Most synthesized compounds showed potent activity against soybean 15-LOX with IC50 values less than 25 μM. The most potent compound 4c (3-methylbenzoyl derivative) with IC50 value of 1.8 μM was 10-fold more potent than quercetin. Interestingly, compound 4c also showed the highest antioxidant activity, as determined by ferric reducing antioxidant power (FRAP) assay. Its capacity for reducing ferric ion was more than ascorbic acid. The viability assay of the selected compound 4c against oxidative stress-induced cell death in differentiated PC12 cells revealed that compound 4c significantly protected neurons against cell death in low concentrations.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam Shahzad
authors.initials: MS
authors.lastname: Shirazi
authors.affiliation: Department of Chemistry, Islamic Azad University, Tehran-North Branch, Zafar St, Tehran, Iran.
authors.forename: Raana
authors.initials: R
authors.lastname: Taherkhani
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Saeedi
authors.affiliation: Department of Chemistry, Islamic Azad University, Tehran-North Branch, Zafar St, Tehran, Iran.
authors.forename: Eskandar
authors.initials: E
authors.lastname: Alipour
authors.affiliation: Neurobiomedical Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Farshad Homayouni
authors.initials: FH
authors.lastname: Moghadam
authors.affiliation: Neurobiomedical Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.affiliation: Neurobiomedical Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.affiliation: Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Loghman
authors.initials: L
authors.lastname: Firoozpour
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: aforoumadi@tums.ac.ir.
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
mesh_terms: D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D013025:Glycine max / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D016859:Lipoxygenase Inhibitors; D006861:Hydrogen Peroxide; D001093:Arachidonate 15-Lipoxygenase
keywords: 15-Lipoxygenase; Antioxidant activity; Docking study; Enzyme inhibitors; Sulfonamides; Thiourea