title: Microwave assisted synthesis of naphthopyrans catalysed by silica supported fluoroboric acid as a new class of non purine xanthine oxidase inhibitors.
abstract: A series of naphthopyrans was synthesized employing silica supported fluoroboric acid under solvent free conditions in a microwave reactor. The catalytic influence of HBF4-SiO2 was investigated in detail to optimize the reaction conditions. The synthesised compounds were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have also been presented. Among the synthesised compounds, NP-17, NP-19, NP-20, NP-23, NP-24, NP-25 and NP-26 were the active inhibitors with an IC50 ranging from 4 to 17 μM. Compound NP-19 with a thiophenyl ring at position 1 emerged as the most potent xanthine oxidase inhibitor (IC50=4 μM) in comparison to allopurinol (IC50=11.10 μM) and febuxostat (IC50=0.025 μM). The basis of significant inhibition of xanthine oxidase by NP-19 was rationalized by its molecular docking at MTE binding site of xanthine oxidase.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
authors.forename: Sahil
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
authors.forename: Kirti
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Ojha
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, India.
authors.forename: Gagandip
authors.initials: G
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, 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 143005, Punjab, India; Sri Sai College of Pharmacy, Badhani, Pathankot 145001, Punjab, India. Electronic address: bedi_preet@yahoo.com.
authors.forename: P M S
authors.initials: PM
authors.lastname: Bedi
mesh_terms: D001881:Borates / Q000138:chemical synthesis* / Q000378:metabolism; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D008872:Microwaves; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000378:metabolism; D011714:Pyrans / Q000138:chemical synthesis* / Q000378:metabolism; D012822:Silicon Dioxide / Q000138:chemical synthesis* / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001881:Borates; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D011714:Pyrans; D012822:Silicon Dioxide; D014969:Xanthine Oxidase; C098759:fluoroboric acid
keywords: Fluoroboric acid; Microwave; Naphthopyrans; Silica; Xanthine oxidase