N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors

Kunal Nepali, Amit Agarwal, Sameer Sapra, Vineet Mittal, Raj Kumar, Uttam C. Banerjee, Manish K. Gupta, Naresh K. Satti, Om P. Suri, Kanaya L. Dhar

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

A series of forty two N-(1,3-diaryl-3-oxopropyl)amides were synthesized via an efficient, modified Dakin-West reaction and were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have been presented. Selected active xanthine oxidase inhibitors (3r, 3s, and 3zh) were assessed in vivo to study their anti-hyperuricemic effect in potassium oxonate induced hyperuricemic mice model. Compound 3s emerged as the most potent xanthine oxidase inhibitor (IC 50 = 2.45 μM) as well as the most potent anti-hyperuricemic agent. The basis of significant inhibition of xanthine oxidase by 3s was rationalized by its molecular docking into catalytic site of xanthine oxidase.

Original languageEnglish
Pages (from-to)5569-5576
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number18
DOIs
Publication statusPublished - Sep 15 2011
Externally publishedYes

Fingerprint

Xanthine Oxidase
Amides
Structure-Activity Relationship
Catalytic Domain

Keywords

  • Molecular docking
  • N-(1,3-Diaryl-3-oxopropyl)amides
  • 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

Nepali, K., Agarwal, A., Sapra, S., Mittal, V., Kumar, R., Banerjee, U. C., ... Dhar, K. L. (2011). N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors. Bioorganic and Medicinal Chemistry, 19(18), 5569-5576. https://doi.org/10.1016/j.bmc.2011.07.039

N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors. / Nepali, Kunal; Agarwal, Amit; Sapra, Sameer; Mittal, Vineet; Kumar, Raj; Banerjee, Uttam C.; Gupta, Manish K.; Satti, Naresh K.; Suri, Om P.; Dhar, Kanaya L.

In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 18, 15.09.2011, p. 5569-5576.

Research output: Contribution to journalArticle

Nepali, K, Agarwal, A, Sapra, S, Mittal, V, Kumar, R, Banerjee, UC, Gupta, MK, Satti, NK, Suri, OP & Dhar, KL 2011, 'N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors', Bioorganic and Medicinal Chemistry, vol. 19, no. 18, pp. 5569-5576. https://doi.org/10.1016/j.bmc.2011.07.039
Nepali, Kunal ; Agarwal, Amit ; Sapra, Sameer ; Mittal, Vineet ; Kumar, Raj ; Banerjee, Uttam C. ; Gupta, Manish K. ; Satti, Naresh K. ; Suri, Om P. ; Dhar, Kanaya L. / N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors. In: Bioorganic and Medicinal Chemistry. 2011 ; Vol. 19, No. 18. pp. 5569-5576.
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