Synthesis and evaluation of naphthoflavones as a new class of non purine xanthine oxidase inhibitors This Letter is dedicated to Dr. K. L. Dhar on the occasion of his 78th birthday.

Harbinder Singh, Sahil Sharma, Ritu Ojha, Manish K. Gupta, Kunal Nepali, P. M.S. Bedi

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4192-4197
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number17
DOIs
Publication statusPublished - Sep 1 2014
Externally publishedYes

Fingerprint

Xanthine Oxidase
Inhibitory Concentration 50
Flavones
Enzyme kinetics
Molecular modeling
Enzymes
Structure-Activity Relationship
Assays
Substitution reactions

Keywords

  • Assay
  • Flavone
  • Inhibitory
  • Kinetics
  • Naphthopyran
  • Xanthine oxidase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Synthesis and evaluation of naphthoflavones as a new class of non purine xanthine oxidase inhibitors This Letter is dedicated to Dr. K. L. Dhar on the occasion of his 78th birthday. / Singh, Harbinder; Sharma, Sahil; Ojha, Ritu; Gupta, Manish K.; Nepali, Kunal; Bedi, P. M.S.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 17, 01.09.2014, p. 4192-4197.

Research output: Contribution to journalArticle

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