2. Academic Validation
  3. Resorcinol-based hemiindigoid derivatives as human tyrosinase inhibitors and melanogenesis suppressors in human melanoma cells

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

  • Eur J Med Chem. 2022 Nov 28;246:114972. doi: 10.1016/j.ejmech.2022.114972.
Brayan Roulier 1,  Inbal Rush 2,  Leticia M Lazinski 3,  Basile Pérès 1,  Hamza Olleik 4,  Guy Royal 5,  Ayelet Fishman 2,  Marc Maresca 4,  Romain Haudecoeur 6
Affiliations

Affiliations

  • 1 Univ. Grenoble Alpes, CNRS 5063, DPM, 38000, Grenoble, France.
  • 2 Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.
  • 3 Univ. Grenoble Alpes, CNRS 5063, DPM, 38000, Grenoble, France; Univ. Grenoble Alpes, CNRS 5250, DCM, 38000, Grenoble, France.
  • 4 Aix Marseille Univ., CNRS, Centrale Marseille, iSm2, 13397, Marseille, France.
  • 5 Univ. Grenoble Alpes, CNRS 5250, DCM, 38000, Grenoble, France.
  • 6 Univ. Grenoble Alpes, CNRS 5063, DPM, 38000, Grenoble, France. Electronic address: Romain.Haudecoeur@univ-grenoble-alpes.fr.
PMID: 36462443 DOI: 10.1016/j.ejmech.2022.114972
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.

Keywords

Aurone; Hemiindigoid; Indanone; Melanogenesis; Melanoma; human Tyrosinase.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z