Synthesis and xanthine oxidase inhibitory activity of 7-methyl-2- (phenoxymethyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives

K. R. Sathisha, Shaukath A. Khanum, J. N.Narendra Sharath Chandra, F. Ayisha, S. Balaji, Gopal K. Marathe, Shubha Gopal, K. S. Rangappa

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

An elevated level of blood uric acid (hyperuricemia) is the underlying cause of gout. Xanthine oxidase is the key enzyme that catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. Allopurinol, a widely used xanthine oxidase inhibitor is the most commonly used drug to treat gout. However, a small but significant portion of the population suffers from adverse effects of allopurinol that includes gastrointestinal upset, skin rashes and hypersensitivity reactions. Moreover, an elevated level of uric acid is considered as an independent risk factor for cardiovascular diseases. Therefore use of allopurinol-like drugs with minimum side effects is the ideal drug of choice against gout. In this study, we report the synthesis of a series of pyrimidin-5-one analogues as effective and a new class of xanthine oxidase inhibitors. All the synthesized pyrimidin-5-one analogues are characterized by spectroscopic techniques and elemental analysis. Four (6a, 6b, 6d and 6f) out of 20 synthesized molecules in this class showed good inhibition against three different sources of xanthine oxidase, which were more potent than allopurinol based on their respective IC50 values. Molecular modeling and docking studies revealed that the molecule 6a has very good interactions with the Molybdenum-Oxygen-Sulfur (MOS) complex a key component in xanthine oxidase. These results highlight the identification of a new class of xanthine oxidase inhibitors that have potential to be more efficacious, than allopurinol, to treat gout and possibly against cardiovascular diseases.

Original languageEnglish
Pages (from-to)211-220
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number1
DOIs
Publication statusPublished - 01-01-2011

Fingerprint

Xanthine Oxidase
Allopurinol
Gout
Derivatives
Uric Acid
Cardiovascular Diseases
Pharmaceutical Preparations
Hyperuricemia
Molecules
Hypoxanthine
Xanthine
Molecular modeling
Molybdenum
Exanthema
Sulfur
Inhibitory Concentration 50
Skin
Hypersensitivity
Blood
Oxygen

All Science Journal Classification (ASJC) codes

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

Cite this

Sathisha, K. R. ; Khanum, Shaukath A. ; Chandra, J. N.Narendra Sharath ; Ayisha, F. ; Balaji, S. ; Marathe, Gopal K. ; Gopal, Shubha ; Rangappa, K. S. / Synthesis and xanthine oxidase inhibitory activity of 7-methyl-2- (phenoxymethyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives. In: Bioorganic and Medicinal Chemistry. 2011 ; Vol. 19, No. 1. pp. 211-220.
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Synthesis and xanthine oxidase inhibitory activity of 7-methyl-2- (phenoxymethyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives. / Sathisha, K. R.; Khanum, Shaukath A.; Chandra, J. N.Narendra Sharath; Ayisha, F.; Balaji, S.; Marathe, Gopal K.; Gopal, Shubha; Rangappa, K. S.

In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 1, 01.01.2011, p. 211-220.

Research output: Contribution to journalArticle

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T1 - Synthesis and xanthine oxidase inhibitory activity of 7-methyl-2- (phenoxymethyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives

AU - Sathisha, K. R.

AU - Khanum, Shaukath A.

AU - Chandra, J. N.Narendra Sharath

AU - Ayisha, F.

AU - Balaji, S.

AU - Marathe, Gopal K.

AU - Gopal, Shubha

AU - Rangappa, K. S.

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