title: 2-Benzamido-4-methylthiazole-5-carboxylic Acid Derivatives as Potential Xanthine Oxidase Inhibitors and Free Radical Scavengers.
abstract: The new chemical entities febuxostat and topiroxostat have been approved by the US Food and Drug Administration, opening new avenues for exploiting different heterocycles other than purines as xanthine oxidase (XO) inhibitors. A different series of substituted 2-benzamido-4-methylthiazole-5-carboxylic acid derivatives (5a-r) was synthesized and characterized by the collective use of IR,1H and13C NMR, and mass spectroscopy, for the treatment of gout and hyperuricemia. In vitro studies of the synthesized derivatives revealed that the presence of a fluoro group at the para position in 5b (IC50 = 0.57 μm) and a chloro group in 5c (IC50 = 0.91 μm) signifies excellent XO inhibitory activity among the series, along with their DPPH free radial scavenging activity. In vivo serum uric acid inhibition studies established that 5b and 5c displayed 62 and 53% uric acid inhibition, respectively. Studies on enzyme kinetics indicated that 5b acts as a mixed type inhibitor. In silico prediction by various softwares also helped in the recognition of potent XO inhibitors.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hamdard University, New Delhi, India.
authors.forename: Md Rahmat
authors.initials: MR
authors.lastname: Ali
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hamdard University, New Delhi, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hamdard University, New Delhi, India.
authors.forename: Obaid
authors.initials: O
authors.lastname: Afzal
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hamdard University, New Delhi, India.
authors.forename: Nishtha
authors.initials: N
authors.lastname: Shalmali
authors.affiliation: Hamdard Institute of Medical Science, Hamdard University, New Delhi, India.
authors.forename: Wazid
authors.initials: W
authors.lastname: Ali
authors.affiliation: Faculty of Pharmacy, Department of Pharmacology, Hamdard University, New Delhi, India.
authors.forename: Manju
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hamdard University, New Delhi, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Bawa
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006074:Gout Suppressants / Q000138:chemical synthesis / Q000494:pharmacology; D062105:Molecular Docking Simulation; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: C000617413:2-(4-chlorobenzamido)-4-methylthiazole-5-carboxylic acid; C000617412:2-(4-fluorobenzamido)-4-methylthiazole-5-carboxylic acid; D001549:Benzamides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006074:Gout Suppressants; D013844:Thiazoles; D014527:Uric Acid; D014969:Xanthine Oxidase
keywords: Febuxostat; Kinetic; Reactive oxygen species; Uric acid; Xanthine oxidase