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

Jakimiuk K., SARI S., Milewski R., Supuran C. T., ŞÖHRETOĞLU D., Tomczyk M.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.37, no.1, pp.421-430, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1080/14756366.2021.2014832
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, Food Science & Technology Abstracts, MEDLINE, Directory of Open Access Journals
  • Page Numbers: pp.421-430
  • Keywords: Flavonoid, molecular docking, tyrosinase, structure-activity relationship, statistical analysis, CRYSTAL-STRUCTURE, MECHANISM, PROTEIN, OXIDASE, QUERCETIN
  • Hacettepe University Affiliated: Yes


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 mu M) 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-gamma-pyrane ring of the flavonoids.