Design, synthesis, and anti-urease evaluations of new sulfonamide-1,2,3-triazole-acetamide derivatives.

The present study demonstrated the design and synthesis of sulfonamide-1,2,3-triazole-acetamide derivatives 11a-o and screening against urease in vitro and in silico. These compounds were designed based on reported potent urease inhibitors and optimized structurally based on substituents on acetamide moiety. In vitro studies showed that all the new compounds 11a-o (IC₅₀ values = 0.12-4.53 µM) were more potent than stand inhibitor thiourea (IC₅₀ value = 23.76 µM). In this regard, the most potent compounds were N-phenylacetamide derivatives 11b, 11f, and 11 h with 2-methyl, 4-methoxy, and 2-fluoro substituents, respectively. In this regard, the most potent compound 11b was 198-folds more potent than thiourea against urease. In silico studies demonstrated that this compound with the binding energy less than thiourea attached to the urease's active site. Druglikeness, pharmacokinetics, and toxicity of compound 11b and thiourea were predicted by two credible online servers. These in silico studies showed that, in terms of druglikeness and pharmacokinetics, compound 11b was almost similar to thiourea while in term of toxicity, compound 11b was better than thiourea.