13520-94-0Relevant academic research and scientific papers
Modulating effects of a novel skin-lightening agent, α-lipoic acid derivative, on melanin production by the formation of DOPA conjugate products
Tsuji-Naito, Kentaro,Hatani, Tomoko,Okada, Takeshi,Tehara, Takao
, p. 1967 - 1975 (2007)
Sodium zinc dihydrolipoylhistidinate (DHLHZn) is a compound of Zn2+/dihydrolipoic acid derivate complex, which was developed for cosmetic/medical use. To characterize DHLHZn as a novel skin-lightening agent, inhibitory actions of DHLHZn on tyrosinase (including its reaction pathway) have been elucidated in this study. In a B16 melanoma cell system, DHLHZn was active in suppressing the synthesis of melanins as well as α-arbutin, well known as a depigmenting drug. Furthermore, in a tyrosinase assay, DHLHZn showed stronger inhibitory effect on DOPAchrome formation than other tyrosinase inhibitors such as kojic acid. Our previous report demonstrated that the sulfhydryl groups of lipoyl motif react with DOPAquinone to form lipoyl DOPA conjugates. We therefore postulated that conjugated products between DHLHZn and DOPAquinone might be formed. Upon reaction of DHLHZn with l-DOPA following tyrosinase-catalyzed oxidation, the formation of DHLH DOPA conjugated products was confirmed by HPLC-tandem mass spectrometry using reserpine as the internal standard. In addition, the inhibitory kinetics analyzed by a Lineweaver-Burk plot exhibited the reversibility of DHLHZn as a competitive inhibitor with a KI value of 0.35 μM. These results indicate that this covalent reaction might contribute to alternating DOPAquinone, which is a tyrosinase reaction product, and result in the competitive inhibitory effect of DHLHZn on DOPAchrome formation. DHLHZn may thus serve as a potentially effective skin-lightening agent, an effectiveness that is based on the compound's covalent scavenging of DOPAquinone resulting in depigmentation.
BIOMIMETIC SYNTHESIS OF 5,6-DIHYDROXYINDOLE-2-CARBOXYLIC ACID AND OF ITS BENZYL ESTER.
Chioccara, Francesco,Novellino, Ettore
, p. 1815 - 1822 (2007/10/02)
Benzyl 5,6-dihydroxyindole-2-carboxylate 3 and the free acid 4 were synthesized by oxidative cyclization of dopa benzyl ester with ceric ammonium nitrate and subsequent removal of the benzyl group by hydrohenation.
A RE-EXAMINATION OF THE ZINC-CATALYSED REARRANGEMENT OF DOPACHROME USING IMMOBILISED TYROSINASE
Napolitano, Alessandra,Chioccara, Francesco,Prota, Giuseppe
, p. 357 - 360 (2007/10/02)
The effect of zinc ions on the rearrangement of dopachrome, 1, has been reinvestigated using an improved technique to obtain the aminochrome which involves aereal oxidation of dopa with mushroom tyrosinase immobilesed on activated sepharose.Zinc-catalysed rearragement of dopachrome thus obtained was found to give 5,6-dihydroxyindole-2-carboxylic acid, 3, mainly, rather than 5,6-dihydroxyindole, 2, as previously reported.Interestingly, the rate of rearrangement and the formation ratio 3/2 are strongly dependent on the amount of metal added, decreasing as zinc concentration is lowered from 10percent to 0.1percent.The relevance of these in vitro experiments is discussed in relation to the role of metallic cations in the biosynthesis of eumelanins.
