Flavonoids as tyrosinase inhibitors in in silico and in vitro models: basic framework of SAR using a statistical modelling approach

Abstract

Flavonoids are widely distributed in plants and constitute the most common polyphenolic phytoconstituents in the human diet. In this study, the in vitro inhibitory activity of 44 different flavonoids (1–44) against mushroom tyrosinase was studied, and an in silico study and type of inhibition for the most active compounds were evaluated too. Tyrosinase inhibitors block melanogenesis and take part in melanin production or distribution leading to pigmentation diseases. The in vitro study showed that quercetin was a competitive inhibitor (IC₅₀=44.38 ± 0.13 µM) and achieved higher antityrosinase activity than the control inhibitor kojic acid. The in silico results highlight the importance of the flavonoid core with a hydroxyl at C7 as a strong contributor of interference with tyrosinase activity. According to the developed statistical model, the activity of molecules depends on hydroxylation at C3 and methylation at C8, C7, and C3 in the benzo-γ-pyrane ring of the flavonoids.

Keywords:

• Flavonoid
• molecular docking
• tyrosinase
• structure-activity relationship
• statistical analysis

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Correction

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (10.1080/14756366.2022.2024999).

Acknowledgement

The authors express thanks to J.W. Strawa and A.M. Juszczak from the Medical University of Białystok for isolation of compounds to in vitro studies.

Author contributions

Study design: K.J, and M.T.; Biological evaluation: K.J.; Data Interpretation: K.J.; Computational studies: S.S., and D.S.; Statistical analysis: R.M., and K.J.; Supervised experiments: M.T., and D.S.; Wrote the original paper: K.J., S.S., and R.M.; Manuscript formal analysis: M.T., and C.T.S.

Disclosure statement

No potential conflict of interest was reported by the authors. CT Supuran is Editor-in-Chief of Journal of Enzyme Inhibition and Medicinal Chemistry and he was not involved in the assessment, peer review or decision making process of this paper. The authors have no relevant affiliations of financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.