Benzoflavone derivatives as potent antihyperuricemic agents

Jatinder V. Singh, Gurbachan Mal, Gurleen Kaur, Manish K. Gupta, Amritpal Singh, Kunal Nepali, Harbinder Singh, Sahil Sharma, S. Preet Mohinder Bedi

Research output: Contribution to journalArticle

7 Citations (Scopus)

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, and NF-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 and NF-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 and NF-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.

Original languageEnglish
Pages (from-to)128-147
Number of pages20
JournalMedChemComm
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Benzoflavone derivatives as potent antihyperuricemic agents'. Together they form a unique fingerprint.

  • Cite this

    Singh, J. V., Mal, G., Kaur, G., Gupta, M. K., Singh, A., Nepali, K., Singh, H., Sharma, S., & Bedi, S. P. M. (2019). Benzoflavone derivatives as potent antihyperuricemic agents. MedChemComm, 10(1), 128-147. https://doi.org/10.1039/c8md00512e