Design, synthesis, docking study and urease inhibitory activity evaluation of novel 2-((5-amino-1,3,4-thiadiazol-2-yl)thio)-N-arylacetamide derivatives

In this paper, novel 2-((5-amino-1,3,4-thiadiazol-2-yl)thio)-N-arylacetamide derivatives (7a–l) are designed, synthesized, and evaluated in vitro for their urease inhibitor activities. The compounds are synthesized efficiently in three steps in high isolated yields from amines, 2-chloroacetyl chloride, hydrazinecarbothioamide, and carbon disulfide. The molecular docking simulation were performed using AutoDock4 by docking all synthesized compound and standard inhibitors into the crystal structure of Jack bean urease. Comparison between the urease inhibitory activity of compounds 7a–l with the IC50 of (2.85–5.83 µM) and thiourea and hydroxyurea as standards inhibitors with the IC50 of (22.00 and 100.00 µM, respectively) proved the high activity of the synthesized compounds against the mentioned enzyme. Docking results were in good agreement with experimental results and indicate that synthesized compounds could interact well with the active site of the urease enzyme and among all; compound 7j shows more favorable interactions with the active site which confirm its great inhibitory activity with IC50 of 2.85 µM. Therefore, compound 7j might be a promising candidate for further evaluation.