title: Synthesis, screening and docking of fused pyrano[3,2-d]pyrimidine derivatives as xanthine oxidase inhibitor.
abstract: In view of developing effective xanthine oxidase (XO) enzyme inhibitors, a series of 100 pyrano[3,2-d]pyrimidine derivatives was synthesized and evaluated for its in vitro XO enzyme inhibition. Structure activity relationship has also been established. Among all the synthesized compounds, 4d, 8d and 9d were found to be the most potent enzyme inhibitors with IC50values of 8μM, 8.5μM and 7μM, respectively. Compound 9d was further investigated in enzyme kinetic studies and the Lineweaver-Burk plot revealed that the compound 9d was mixed type inhibitor. Molecular properties of the most potent compounds 4d, 8d and 9d, have also been calculated. Docking study was performed to investigate the recognition pattern between xanthine oxidase and the most potent XO inhibitor, 9d. The study suggests that 9d may block the activity of XO sufficiently enough to prevent the substrate from binding to its active site.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Manroopraj
authors.initials: M
authors.lastname: Kaur
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Amandeep
authors.initials: A
authors.lastname: Kaur
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Suhani
authors.initials: S
authors.lastname: Mankotia
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Harbinder
authors.initials: H
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Arshdeep
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Jatinder Vir
authors.initials: JV
authors.lastname: Singh
authors.affiliation: Lloyd Institute of Management and Technology, Greater Noida, UP, India.
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Gupta
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India. Electronic address: ss.gq2009@gmail.com.
authors.forename: Sahil
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Kunal
authors.initials: K
authors.lastname: Nepali
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Preet Mohinder Singh
authors.initials: PMS
authors.lastname: Bedi
mesh_terms: D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008892:Milk / Q000201:enzymology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011714:Pyrans; D011743:Pyrimidines; C476007:pyrano(2,3-d)pyrimidine; D014969:Xanthine Oxidase
keywords: Enzyme kinetics; Lineweaver-Burk plot; Molecular modeling studies; Pyrano[3,2-d]pyrimidine; Xanthine oxidase enzyme