PHARMACOLOGICAL INVESTIGATIONS BASED ON NOVEL TRIAZOLE COMPOUNDS: MOLECULAR MODELING AND ADMET ANALYSIS
Keywords:
Hyperuricemia, gout, xanthine oxidase, CoMFA, CoMSIA, molecular docking, ADMET, allopurinol, febuxostat, topiroxostat, 4-(phenoxymethyl)-1H-1,2,3-triazole derivatives.Abstract
In the treatment of hyperuricemia and gout, inhibition of xanthine oxidase enzyme activity is considered a key therapeutic approach. In this study, the xanthine oxidase inhibitory activity of 4-(phenoxymethyl)-1H-1,2,3-triazole derivatives is evaluated based on molecular modeling. QSAR models were developed using CoMFA and CoMSIA methods, and their reliability was confirmed by internal and external validation. Molecular docking and dynamic analyses revealed that the most active molecules — No. 8 and No. 22 — form stable interactions with the xanthine oxidase enzyme. Additionally, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the newly proposed compounds Pred 4 and Pred 5 were studied, showing favorable pharmacokinetic and toxicological profiles for drug use. The obtained results indicate that the Pred 4 and Pred 5 molecules may be promising candidates for the treatment of hyperuricemia and gout.
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