Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: in vitro and in silico studies

Abstract

Tyrosinase, a pivotal enzyme in melanin synthesis, is a primary target for the development of depigmenting agents. In this work, in vitro and in silico techniques were employed to identify novel tyrosinase inhibitors from a set of 12 anilino-1,4-naphthoquinone derivatives. Results from the mushroom tyrosinase activity assay indicated that, among the 12 derivatives, three compounds (1, 5, and 10) demonstrated the most significant inhibitory activity against mushroom tyrosinase, surpassing the effectiveness of the kojic acid. Molecular docking revealed that all studied derivatives interacted with copper ions and amino acid residues at the enzyme active site. Molecular dynamics simulations provided insights into the stability of enzyme–inhibitor complexes, in which compounds 1, 5, and particularly 10 displayed greater stability, atomic contacts, and structural compactness than kojic acid. Drug likeness prediction further strengthens the potential of anilino-1,4-naphthoquinones as promising candidates for the development of novel tyrosinase inhibitors for the treatment of hyperpigmentation disorders.

Graphical Abstract

Keywords:

• Tyrosinase inhibition
• anilino-14-naphthoquinones
• molecular docking
• molecular dynamics simulations

Author contributions

P.M.: conceptualisation. S.S., S.N., N.K., and P.M.: investigation, formal analysis, and methodology. S.S., S.N., P.M., and R.P.: data curation, validation, and visualisation. S.S. and P.M.: writing – original draft, writing – review and editing. P.M.: funding acquisition and project administration. P.M. and A.S.: supervision. P.M., A.S., R.P., and T.R.: resources. R.P.: chemical synthesis. T.R.: software. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors report no conflicts of interest.

Data availability statement

The datasets presented in the current study are available upon reasonable request.

Additional information

Funding

This project is financially supported by the Fundamental Fund of Khon Kaen University and National Science, Research and Innovation Fund (NSRF). S.S. was supported by a Postgraduate Study Support Grant of Faculty of Medicine, Khon Kaen University. R.P. thanks Srinakharinwirot University and National Science, Research and Innovation Fund (NSRF) (Fundamental Fund: Grant No. 029/2566).