title: Development of 2-(Substituted Benzylamino)-4-Methyl-1, 3-Thiazole-5-Carboxylic Acid Derivatives as Xanthine Oxidase Inhibitors and Free Radical Scavengers.
abstract: A series of 2-(substituted benzylamino)-4-methylthiazole-5-carboxylic acid was designed and synthesized as structural analogue of febuxostat. A methylene amine spacer was incorporated between the phenyl ring and thiazole ring in contrast to febuxostat in which the phenyl ring was directly linked with the thiazole moiety. The purpose of incorporating methylene amine was to provide a heteroatom which is expected to favour hydrogen bonding within the active site residues of the enzyme xanthine oxidase. The structure of all the compounds was established by the combined use of FT-IR, NMR and MS spectral data. All the compounds were screened in vitro for their ability to inhibit the enzyme xanthine oxidase as per the reported procedure along with DPPH free radical scavenging assay. Compounds 5j, 5k and 5l demonstrated satisfactory potent xanthine oxidase inhibitory activities with IC50 values, 3.6, 8.1 and 9.9 μm, respectively, whereas compounds 5k, 5n and 5p demonstrated moderate antioxidant activities having IC50 15.3, 17.6 and 19.6 μm, respectively, along with xanthine oxidase inhibitory activity. Compound 5k showed moderate xanthine oxidase inhibitory activity as compared with febuxostat along with antioxidant activity. All the compounds were also studied for their binding affinity in active site of enzyme (PDB ID-1N5X).
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Md Rahmat
authors.initials: MR
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Obaid
authors.initials: O
authors.lastname: Afzal
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Nishtha
authors.initials: N
authors.lastname: Shalmali
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Manju
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Bawa
mesh_terms: D002264:Carboxylic Acids / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D017550:Spectroscopy, Fourier Transform Infrared; D014969:Xanthine Oxidase / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D014969:Xanthine Oxidase
keywords: febuxostat; free radical; methylene amine; molecular docking; xanthine oxidase