title: Synthesis and evaluation of naphthoflavones as a new class of non purine xanthine oxidase inhibitors.
abstract: In view of reported xanthine oxidase inhibitory potential of naphthopyrans and flavones, naphthoflavones as hybrids of the two were designed, synthesized and evaluated for in vitro xanthine oxidase inhibitory activity in the present study. The results of the assay revealed that the naphthoflavones possess promising inhibitory potential against the enzyme with IC50 values ranging from 0.62 to 41.2 μM. Structure activity relationship indicated that the nature and placement of substituents on the phenyl ring at 2nd position remarkably influences the inhibitory activity. Substitution of halo and nitro groups at ortho and para position of the phenyl ring (2nd position) remarkably favored the activity. NF-4 with p-fluoro phenyl ring was the most potent inhibitor with IC50 value of 0.62 μM. Enzyme kinetics study was also performed to investigate the inhibition mechanism and it was found that the naphthoflavones displayed mixed type inhibition. The basis of significant inhibition of xanthine oxidase by NF-4 was rationalized by molecular modeling studies.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: Harbinder
authors.initials: H
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: Sahil
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Ojha
authors.affiliation: Department of pharmaceutical sciences, ISF College of pharmacy, Punjab, India; Lloyd Institute of Management and Technology, Greater Noida (UP), India.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Gupta
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India. Electronic address: kunal_8855@rediffmail.com.
authors.forename: Kunal
authors.initials: K
authors.lastname: Nepali
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: P M S
authors.initials: PM
authors.lastname: Bedi
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047309:Flavones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008892:Milk / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D047309:Flavones; D014969:Xanthine Oxidase
keywords: Assay; Flavone; Inhibitory; Kinetics; Naphthopyran; Xanthine oxidase