Synthesis and Evaluation of Isatin Analogs as Potential Urease and Tyrosinase Inhibitors: An Approach of Molecular Docking.

Abstract

A series of isatin-based Schiff base derivatives (1-12) was synthesized via a two-step reaction and characterized using spectroscopic techniques such as ¹H-NMR and mass spectrometry. The urease and tyrosinase inhibitory activities of the synthesized compounds were evaluated using thiourea (IC50 = 21.25 ± 0.15 µM) and kojic acid (IC50 = 121 ± 0.5 µM) as standard inhibitors. Among the synthesized analogs, only three compounds-1 (IC50 = 38.9 ± 0.06 µM), 3 (IC50 = 56.7 ± 0.02 µM), and 10 (IC50 = 71 ± 0.09 µM) showed moderate urease inhibition, while the remaining compounds were inactive. All compounds were inactive against tyrosinase inhibition. The structure-activity relationship (SAR) of the active analogs was established based on the nature, position, and number of substituents on the phenyl ring of the basic nucleus of the compounds. Molecular docking studies were performed to confirm the binding interactions of the most potent analogs with the active site of urease. The docking results revealed that compound 1 formed six strong intermolecular interactions with the binding site residues of urease, exhibiting the lowest docking score of -4.8944. The findings suggest that the synthesized isatin-based Schiff base derivatives, particularly compounds 1, 3, and 10, could serve as potential lead compounds for developing novel urease inhibitors.