Structural Requirements of Alkylglyceryl-l-Ascorbic Acid Derivatives for Melanogenesis Inhibitory Activity
| Autor: | Osamu Muraoka, Norihisa Taira, Masato Yoshioka, Yushi Katsuyama, Toshio Morikawa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Tyrosinase Skin Lightening Preparations 3-O-(2 3-dihydroxypropyl)-2-O-hexyl-l-ascorbic acid Quantitative Structure-Activity Relationship Ascorbic Acid Alkylation Melanin alkylglyceryl lcsh:Chemistry chemistry.chemical_compound Mice 0302 clinical medicine lcsh:QH301-705.5 Spectroscopy melanogenesis inhibitor Chemistry 3-O-(2 3-dihydroxypropyl)-2-O-hexyl General Medicine Computer Science Applications Biochemistry 030220 oncology & carcinogenesis Melanocytes medicine.symptom Vitamin Inhibitory postsynaptic potential Catalysis Article Cell Line Inorganic Chemistry 03 medical and health sciences structural requirement Cell Line Tumor medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology IC50 Melanins Organic Chemistry 2-O-(2 3-dihydroxypropyl)-3-O-hexyl-l-ascorbic acid Ascorbic acid 3-dihydroxypropyl)-2-O-hexyl-2-O-(2 3-dihydroxypropyl)-3-O-hexyl-mechanism of action 030104 developmental biology Mechanism of action 2-O-(2 3-dihydroxypropyl)-3-O-hexyl lcsh:Biology (General) lcsh:QD1-999 alkylglyceryl-l-ascorbic acid |
| Zdroj: | International Journal of Molecular Sciences; Volume 19; Issue 4; Pages: 1144 International Journal of Molecular Sciences, Vol 19, Iss 4, p 1144 (2018) International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms19041144 |
| Popis: | l-Ascorbic acid has multifunctional benefits on skin aesthetics, including inhibition of melanin production, and is widely used in cosmetics. It, however, has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l-ascorbic acid derivatives, highly stable vitamin C–alkylglycerol conjugates, would have similar anti-melanogenic activity with better stability and penetration. We test 28 alkylglyceryl-l-ascorbic acid derivatives (1–28) on theophylline-stimulated B16 melanoma 4A5 cells to determine if they inhibit melanogenesis and establish any structure–function relationships. Although not the most potent inhibitors, 3-O-(2,3-dihydroxypropyl)-2-O-hexyl-l-ascorbic acid (6, IC50 = 81.4 µM) and 2-O-(2,3-dihydroxypropyl)-3-O-hexyl-l-ascorbic acid (20, IC50 = 117 µM) are deemed the best candidate derivatives based on their inhibitory activities and low toxicities. These derivatives are also found to be more stable than l-ascorbic acid and to have favorable characteristics for skin penetration. The following structural requirements for inhibitory activity of alkylglyceryl-l-ascorbic acid derivatives are also determined: (i) alkylation of glyceryl-l-ascorbic acid is essential for inhibitory activity; (ii) the 3-O-alkyl-derivatives (2–14) exhibit stronger inhibitory activity than the corresponding 2-O-alkyl-derivatives (16–28); and (iii) derivatives with longer alkyl chains have stronger inhibitory activities. Mechanistically, our studies suggest that l-ascorbic acid derivatives exert their effects by suppressing the mRNA expression of tyrosinase and tyrosine-related protein-1. |
| Databáze: | OpenAIRE |
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