Benzoflavone derivatives as potent antihyperuricemic agents. Issue 1 (21st December 2018)

• Record Type: Journal Article
• Authors: Singh, Jatinder V.; Mal, Gurbachan; Kaur, Gurleen; Gupta, Manish K.; Singh, Amritpal; Nepali, Kunal; Singh, Harbinder; Sharma, Sahil; S. Bedi, Preet Mohinder
• Is Part Of: MedChemComm. Volume 10:Issue 1(2019)
• Page Start: 128
• Page End: 147
• Publication Date: 2018-12-21
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c8md00512e
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Benzoflavone derivatives were rationally designed, synthesized and evaluated against the xanthine oxidase enzyme to check their antihyperuricemic effect by using in vitro as well as in vivo methods. Abstract : Two series of benzoflavone derivatives were rationally designed, synthesized and evaluated for their xanthine oxidase (XO) inhibitory potential. Among both series, eight compounds (NF-2, NF-4, NF-9, NF-12, NF-16, NF-25, NF-28, andNF-32 ) were found to exert significant XO inhibition with IC50 values lower than 10 μM. Enzyme kinetic studies revealed that the most potent benzoflavone derivatives (NF-4 andNF-28 ) are mixed type inhibitors of the XO enzyme. Molecular modeling studies were also performed to investigate the binding interactions of these molecules (NF-4 andNF-28 ) with the amino acid residues present in the active site of the enzyme. Docking results confirmed that their favorable binding conformations in the active site of XO can completely block the catalytic activity of the enzyme. Benzoflavone derivatives exhibiting potent XO enzyme inhibition also showed promising results in a hyperuricemic mice model when tested in vivo .