Synthesis and Biological Evaluation of Resveratrol Derivatives as Melanogenesis Inhibitors

Abstract

Resveratrol (1), a naturally occurring stilbene compound, has been suggested as a potential whitening agent with strong inhibitory activity on melanin synthesis. However, the use of resveratrol in cosmetics has been limited due to its chemical instability and poor bioavailability. Therefore, resveratrol derivatives were prepared to improve bioavailability and anti-melanogenesis activity. Nine resveratrol derivatives including five alkyl ether derivatives with C2H5, C4H9, C5H11, C6H13, and C8H17 (2a-2e) and four ester derivatives with CH3, CH=C(CH3)2, CH(C2H5)C4H9, C7H15 (3a-3d) were newly synthesized and their effect on melanin synthesis were assessed. All the synthetic derivatives efficiently reduced the melanin content in α-MSH stimulated B16F10 melanoma cells. Further investigation showed that the inhibitory effect of 2a on melanin synthesis was achieved not by the inhibition of tyrosinase activity but by the inhibition of melanogenic enzyme expressions such as tyrosinase and tyrosinase-related protein (TRP)-1. Our synthetic resveratrol derivatives have more lipophilic properties than resveratrol by the addition of alkyl or acyl chains to free hydroxyl moiety of resveratrol; thus, they are expected to show better bioavailability in skin application. Therefore, we suggest that our synthetic resveratrol derivatives might be promising candidates for better practical application to skin-whitening cosmetics.

Attenuation of Oxidative Stress in HEK 293 Cells by the TCM Constituents Schisanhenol, Baicalein, Resveratrol or Crocetin and Two Defined Mixtures

“…Thus, five novel alkyl ether (ethyl, butyl, pentyl, hexyl and octyl) derivatives of Res were recently prepared which increased bioavailability compared to Res. Significantly, these derivatives retained the pharmacodynamic (melanogenesis inhibition) effect of Res evaluated (60) so that a mixture of Res and Alkyl-O-Res could be formulated to have both immediate and more prolonged biological activity based on rate of metabolic elimination and unmasking of antioxidant phenolic groups over time. In this respect, the metabolism of the ethyl ether would be more rapid than with any of the other alkyl ethers, with O-deoctylation being the slowest P450-catalyzed reaction in this series.…”

N-(4-methoxyphenyl) caffeamide-induced melanogenesis inhibition mechanisms

“…Quercetin and vanillic acid inhibited α-MSH induced the expression of MITF, tyrosinase, TRP-1, and TRP-2, causing melanogenesis inhibition [35, 36]. Resveratrol derivatives inhibited melanin synthesis through the inhibition of melanogenic enzyme expressions such as tyrosinase and TRP-1 [37]. Our results indicated that K36E inhibited tyrosinase activity and α-MSH-induced protein expression, thereby suppressing melanin biosynthesis.…”

Facile Synthesis and Cytotoxic Activity of the First Ferrocene-Resveratrol Conjugate

“…WING to its therapeutic and protective role, resveratrol [3,5,4'-trihydroxystilbene (RSV) (Figure 1a)] came into focus of research in recent years. Among numerous health benefits, RSV improves cardioprotection, cancer prevention and therapy, immune regulation and metabolic and neuroprotective functions.…”

“…[1−3] In order to enhance its activity, RSV was derivatized by: (i) modification of the number and position of the phenolic groups, (ii) insertion of a long alkyl chains or functionalized chains [4] and (iii) the addition of acyl chains to free hydroxyl groups. [5] The improved biological activity of the so-obtained RSV derivatives in comparison to those of the parent molecule is likely to be due to their lipophilicity and facilitated transport through cell membrane. Recently, RSV-derivatives I and II containing lipophilic ferrocene moiety instead of one benzene ring were synthesized (Figure 1b).…”