Journal
MEDICINAL CHEMISTRY RESEARCH
Volume 29, Issue 1, Pages 83-93Publisher
SPRINGER BIRKHAUSER
DOI: 10.1007/s00044-019-02461-y
Keywords
Thiazole derivatives; Xanthine oxidase inhibition; Enzyme kinetics; Molecular modeling
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Funding
- University Grants Commission under Rajiv Gandhi National Fellowship (RGNF), National Fellowship for Other Backward Classes (NFOBC)
- Council of Scientific & Industrial Research (CSIR)
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A series of 22 compounds of thiazole-5-carboxylic acid derivatives was rationally designed and synthesized. All the compounds were characterized by using H-1 and C-13 NMR and tested against xanthine oxidase enzyme by spectrophotometric assay. Majority of the compounds were found active against the enzyme amongst which GK-20 with an IC50 value of 0.45 mu M was found to be most potent. Structure-activity relationship obtained from the biological results revealed that the di-substituted compounds as Ring B were more potent than that of mono-substituted derivatives. Para-substitution on Ring B is crucial for the xanthine oxidase inhibitory potential. Enzyme kinetic studies further revealed their mixed type inhibition behavior. Moreover, the binding pattern of the most potent compound GK-20 within the febuxostat binding site of the enzyme was further analyzed by using docking studies which revealed that it sufficiently block the catalytic active site, which prevents the substrate to bind.
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