Synthesis and biological assessment of novel 4H-chromene-3-carbonitrile derivatives as tyrosinase inhibitors

Abstract

Excessive activity of the tyrosinase enzyme during melanogenesis results in hyperpigmentation in the skin. To address this issue, there is a need to develop effective tyrosinase inhibitors as a treatment for hyperpigmentation. In this study, we synthesized some novel 4 H -chromene-3-carbonitrile compounds ( 6a-o ) and assessed their inhibitory activities against tyrosinase, comparing them with kojic acid, which is known as a positive control. Compound 6f emerged as the most effective inhibitor, with an IC 50 of 35.38 ± 2.12 µM. Kinetic studies of 6f exhibited competitive inhibition, with K i = 16.15 µM. Molecular docking studies highlighted the importance of π-π stacking and hydrogen bonding interactions within the binding site. Molecular dynamics simulations showed that the R -enantiomer 6f exhibited superior binding stability compared to the S -enantiomer, with a lower standard deviation of RMSD and more persistent interactions with the key active site residues. These findings underscore the potential of the R -enantiomer of compound 6f as a potent tyrosinase inhibitor and provide insights for developing effective treatments for hyperpigmentation and related skin conditions. Supplementary Information The online version contains supplementary material available at 10.1186/s13065-024-01305-0.