A rational approach for the design and synthesis of 1-acetyl-3,5-diaryl-4, 5-dihydro(1H)pyrazoles as a new class of potential non-purine xanthine oxidase inhibitors

Kunal Nepali, Gurinderdeep Singh, Anil Turan, Amit Agarwal, Sameer Sapra, Raj Kumar, Uttam C. Banerjee, Prabhakar K. Verma, Naresh K. Satti, Manish K. Gupta, Om P. Suri, K. L. Dhar

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Xanthine oxidase is a complex molybdoflavoprotein that catalyses the hydroxylation of xanthine to uric acid. Fifty three analogues of 1-acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles were rationally designed and synthesized and evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Some notions about structure activity relationships are presented. Six compounds 41, 42, 44, 46, 55 and 59 were found to be most active against XO with IC50 ranging from 5.3 μM to 15.2 μM. The compound 59 emerged as the most potent XO inhibitor (IC50 = 5.3 μM). Some of the important interactions of 59 with the amino acid residues of active site of XO have been figured out by molecular modeling.

Original languageEnglish
Pages (from-to)1950-1958
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number6
DOIs
Publication statusPublished - Mar 15 2011
Externally publishedYes

Fingerprint

Pyrazoles
Xanthine Oxidase
Inhibitory Concentration 50
Hydroxylation
Xanthine
Molecular modeling
Structure-Activity Relationship
Uric Acid
Catalytic Domain
Amino Acids

Keywords

  • 1-Acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles
  • Molecular docking
  • Non-purine xanthine oxidase inhibitors
  • Xanthine oxidase

ASJC Scopus subject areas

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

Cite this

A rational approach for the design and synthesis of 1-acetyl-3,5-diaryl-4, 5-dihydro(1H)pyrazoles as a new class of potential non-purine xanthine oxidase inhibitors. / Nepali, Kunal; Singh, Gurinderdeep; Turan, Anil; Agarwal, Amit; Sapra, Sameer; Kumar, Raj; Banerjee, Uttam C.; Verma, Prabhakar K.; Satti, Naresh K.; Gupta, Manish K.; Suri, Om P.; Dhar, K. L.

In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 6, 15.03.2011, p. 1950-1958.

Research output: Contribution to journalArticle

Nepali, Kunal ; Singh, Gurinderdeep ; Turan, Anil ; Agarwal, Amit ; Sapra, Sameer ; Kumar, Raj ; Banerjee, Uttam C. ; Verma, Prabhakar K. ; Satti, Naresh K. ; Gupta, Manish K. ; Suri, Om P. ; Dhar, K. L. / A rational approach for the design and synthesis of 1-acetyl-3,5-diaryl-4, 5-dihydro(1H)pyrazoles as a new class of potential non-purine xanthine oxidase inhibitors. In: Bioorganic and Medicinal Chemistry. 2011 ; Vol. 19, No. 6. pp. 1950-1958.
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