title: Synthesis and xanthine oxidase inhibitory activity of 5,6-dihydropyrazolo/pyrazolo[1,5-c]quinazoline derivatives.
abstract: Some 5,6-dihydropyrazolo/pyrazolo[1,5-c]quinazoline derivatives were rationally designed, synthesized and evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Some notions about structure activity relationships are presented. The compounds 6g, 6h and 6e were found to be significantly active against XO. The compound 6g emerged as the most potent XO inhibitor as compared to allopurinol and free radical scavenger. The molecular docking of 6g into the XO active site highlighted its mode of binding and important interactions such as hydrogen bonding, π-π stacking with amino acid residues like Ser876, Thr1010, Phen914, Phe1009 and Phe649 and its close proximity to dioxothiomolybdenum (MOS).
authors.affiliation: Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, India.
authors.forename: Deependra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, India.
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Kaur
authors.affiliation: Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Negi
authors.affiliation: Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Centre for Genetic Diseases and Molecular Medicine, Central University of Punjab, Bathinda 151 001, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Singh
authors.affiliation: Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, India. Electronic address: raj.khunger@gmail.com.
authors.forename: Raj
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D011720:Pyrazoles; D011799:Quinazolines; C583525:pyrazolo(1,5-c)quinazoline; D000493:Allopurinol; D014969:Xanthine Oxidase
keywords: 5,6-Dihydropyrazolo/pyrazolo[1,5-c]quinazoline; Antioxidant; Synthesis Molecular modeling; Xanthine oxidase