Potent α-glucosidase and tyrosinase inhibition by thiophene-based Schiff bases: Experimental and computational evaluation

Abstract

In this study, novel thiophene-based Schiff base derivatives were synthesized, and their structures were comprehensively analyzed. The inhibitory potentials of these compounds on α-glucosidase and tyrosinase enzymes were systematically evaluated. Among the thiophene-based Schiff bases, compound 8 exhibited moderate inhibitory activity against both α-glucosidase and tyrosinase, with IC50 values of 173.29 and 69.32 µM for each, compared to the positive controls acarbose and kojic acid, respectively. The DFT approach was used to analyze the reactivity and molecular electrostatic potential maps of the compounds, and molecular docking studies for the most active compounds 4 , 6 , and 8 were conducted on both the fungal tyrosinase and Saccharomyces cerevisiae protein models. Furthermore, ADME (Absorption, Distribution, Metabolism, and Excretion) analyses were performed to evaluate their pharmacokinetic profiles and predict their potential bioavailability with basic drug-like properties, and these observations demonstrate the potential importance of the compounds in the field of treating diabetes and skin diseases.