Discovery of (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide among N-substituted cinnamamide derivatives as a novel cosmetic ingredient for hyperpigmentation.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier
      Original Publication: New York, London, Academic Press.
    • Subject Terms:
      Hyperpigmentation*/drug therapy ; Monophenol Monooxygenase*/antagonists & inhibitors ; Monophenol Monooxygenase*/metabolism ; Cinnamates*/chemistry ; Cinnamates*/pharmacology ; Cinnamates*/chemical synthesis ; Cosmetics*/chemistry ; Cosmetics*/pharmacology ; Melanins*/metabolism; Humans ; Animals ; Mice ; Structure-Activity Relationship ; Molecular Structure ; Dose-Response Relationship, Drug ; Acrylamide/chemistry ; Acrylamide/pharmacology ; Drug Discovery ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/chemical synthesis ; Agaricales
    • Abstract:
      Hyperpigmentation disorders may result from inappropriate melanin deposition and/or excessive melanin synthesis. They are classified mainly as aesthetic problems, but they can significantly affect human health by decreasing self-esteem. There are available only limited treatment options for hyperpigmentation disorder, among others, cosmetic products applied topically. Depigmenting ingredients were found to be ineffective and characterized by various side effects. As a result, many efforts are made to discover novel, potent, and safe melanogenesis inhibitors for possible use in topical cosmetic depigmenting formulations. Cinnamic acid derivatives constitute a widely tested group for that purpose. This article reports research in the group of N-alkyl cinnamamide derivatives (un)substituted in phenyl ring. Among tested series, (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide (compound 21) showed the most promising inhibitory properties in mushroom tyrosinase assay (IC 50  = 36.98 ± 1.07 µM for monophenolase activity, IC 50  = 146.71 ± 16.82 µM for diphenolase activity) and melanin production inhibition in B16F10 mouse melanoma cell line at concentration 6.25 µM resulting probably from decreasing of Tyr, Mitf, Tyrp-1, and Tyrp-2 genes expression. This compound also showed melanin production inhibitory properties in pigmented reconstructed human epidermis when used in 1 % and 2 % solutions in 50 % PEG400. In vitro evaluation of its safety profile showed no cytotoxicity to human keratinocytes HaCaT, human skin fibroblasts BJ, and human primary epidermal melanocytes HEMa, no mutagenicity in the Ames test, no genotoxicity in micronucleus test, no phototoxicity, as well as no skin irritation potential tested in PEG400 solution. This compound was also shown to penetrate across the epidermis to reach the possible site of action. The performed research led to classify (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide as a novel potential depigmenting cosmetic ingredient.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Cinnamamide; Cinnamic acid derivatives; Hyperpigmentation; Melanogenesis inhibition; Reconstructed human epidermis; Tyrosinase inhibition
    • Accession Number:
      EC 1.14.18.1 (Monophenol Monooxygenase)
      0 (Cinnamates)
      Y0JET56H7N (cinnamamide)
      0 (Cosmetics)
      0 (Melanins)
      20R035KLCI (Acrylamide)
      0 (Enzyme Inhibitors)
    • Publication Date:
      Date Created: 20240615 Date Completed: 20240719 Latest Revision: 20240722
    • Publication Date:
      20240722
    • Accession Number:
      10.1016/j.bioorg.2024.107533
    • Accession Number:
      38878750