title: 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.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Korea. liuqing7115@hotmail.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: RNS Inc., Yuseong-Gu, Daejeon 34182, Korea. happilion@rns.co.kr.
authors.forename: CheongTaek
authors.initials: C
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Korea. qow0125@naver.com.
authors.forename: Yang Hee
authors.initials: YH
authors.lastname: Jo
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Korea. suntiger85@hanmail.net.
authors.forename: Seon Beom
authors.initials: SB
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Korea. byhwang@chungbuk.ac.kr.
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Korea. mklee@chungbuk.ac.kr.
authors.forename: Mi Kyeong
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000818:Animals; D001682:Biological Availability; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008543:Melanins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D000077185:Resveratrol; D062327:Skin Lightening Preparations / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D013267:Stilbenes / Q000819:agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D008543:Melanins; D008562:Membrane Glycoproteins; D062327:Skin Lightening Preparations; D013267:Stilbenes; D000521:alpha-MSH; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase; D000077185:Resveratrol
keywords: melanin; resveratrol derivatives; tyrosinase; tyrosinase-related protein (TRP)-1