Abstract
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.
Highlights
Melanin is a broad term for a group of natural pigments found in bacteria, fungi, plants, and animals
In our previous investigation of compounds from several natural resources possessing melanogenesis inhibitory activity, we reported that dimeric pyrrolidinoindoline- [20], aporphine- [21,22], benzylisoquinoline- [22], and phenanthridine-type [23] alkaloids, as well as phenylethanoid glycosides [23], methoxyflavones [24], phenylpropanoids [25], neolignans [25], and diterpenes [26,27] exhibited significant positive effects against theophylline-stimulated melanogenesis in B16 melanoma 4A5 cells
We examine the inhibitory effects of 28 alkylglyceryl-ascorbic acid (AsA) derivatives (1–28) on theophylline-stimulated murine B16 melanoma 4A5 cells
Summary
Melanin is a broad term for a group of natural pigments found in bacteria, fungi, plants, and animals. Melanocytes are known to be stimulated by various factors including UV radiation [14], POMC-derived α-melanocyte-stimulating hormone (α-MSH), and other neuropeptides [7,15,16,17], and phosphodiesterase inhibitors, such as theophylline [18]. Stimulation by these factors increases melanin production using L-tyrosine and L-3,4-dihydroxyphenylalanine (L-DOPA) as substrates through various mechanisms of action [7,19]. Existing water-soluble AsA derivatives, which were developed to improve its stability [30,32], have low skin penetration. We examine the inhibitory effects of these amphiphilic AsA derivatives (1–28) on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
