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

3 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

Fingerprint

Gout Suppressants
Benzoflavones
Xanthine Oxidase
Derivatives
Enzyme inhibition
Enzymes
Catalytic Domain
Enzyme kinetics
Molecular modeling
Inhibitory Concentration 50
Conformations
Catalyst activity
Amino Acids
Molecules

ASJC Scopus subject areas

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

Cite this

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

Benzoflavone derivatives as potent antihyperuricemic agents. / Singh, Jatinder V.; Mal, Gurbachan; Kaur, Gurleen; Gupta, Manish K.; Singh, Amritpal; Nepali, Kunal; Singh, Harbinder; Sharma, Sahil; Bedi, S. Preet Mohinder.

In: MedChemComm, Vol. 10, No. 1, 01.01.2019, p. 128-147.

Research output: Contribution to journalArticle

Singh, JV, Mal, G, Kaur, G, Gupta, MK, Singh, A, Nepali, K, Singh, H, Sharma, S & Bedi, SPM 2019, 'Benzoflavone derivatives as potent antihyperuricemic agents', MedChemComm, vol. 10, no. 1, pp. 128-147. https://doi.org/10.1039/c8md00512e
Singh JV, Mal G, Kaur G, Gupta MK, Singh A, Nepali K et al. Benzoflavone derivatives as potent antihyperuricemic agents. MedChemComm. 2019 Jan 1;10(1):128-147. https://doi.org/10.1039/c8md00512e
Singh, Jatinder V. ; Mal, Gurbachan ; Kaur, Gurleen ; Gupta, Manish K. ; Singh, Amritpal ; Nepali, Kunal ; Singh, Harbinder ; Sharma, Sahil ; Bedi, S. Preet Mohinder. / Benzoflavone derivatives as potent antihyperuricemic agents. In: MedChemComm. 2019 ; Vol. 10, No. 1. pp. 128-147.
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