Resorcinol-based hemiindigoid derivatives as human tyrosinase inhibitors and melanogenesis suppressors in human melanoma cells

Brayan Roulier, Inbal Rush, Leticia M. Lazinski, Basile Pérès, Hamza Olleik, Guy Royal, Ayelet Fishman, Marc Maresca, Romain Haudecoeur

Research output: Contribution to journalArticlepeer-review

Abstract

Human tyrosinase (hsTYR) catalyzes the key steps of melanogenesis, making it a privileged target for reducing melanin production in vivo. However, very few hsTYR inhibitors have been reported so far in the literature, whereas thousands of mushroom tyrosinase (abTYR) inhibitors are known. Yet, as these enzymes are actually very different, including at their active sites, there is an urgent need for new true hsTYR inhibitors in order to enable human-directed pharmacological and dermocosmetic applications without encountering the inefficiency and toxicity issues currently triggered by kojic acid or hydroquinone. Starting from the two most active compounds reported to date, i.e. a 2-hydroxypyridine-embedded aurone and thiamidol, we combined herein key structural elements and developed new nanomolar hsTYR inhibitors with cell-based activity. From a complete series of thirty-eight synthesized derivatives, excellent inhibition values were obtained for two compounds in both human melanoma cell lysates and purified hsTYR assays, and a promising improvement was observed in whole cell experiments.

Original languageEnglish
Article number114972
JournalEuropean Journal of Medicinal Chemistry
Volume246
DOIs
StatePublished - 15 Jan 2023

Keywords

  • Aurone
  • Hemiindigoid
  • Indanone
  • Melanogenesis
  • Melanoma
  • human Tyrosinase

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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