Synthesis and anti-melanogenic effects of lipoic acid-polyethylene glycol ester
Authors: Kim, Jin-Hwa1; Sim, Gwan-Sub1; Bae, Jun-Tae1; Oh, Jung-Young1; Lee, Geun-Su1; Lee, Dong-Hwan1; Lee, Bum-Chun2; Pyo, Hyeong-Bae1
Source: Journal of Pharmacy and Pharmacology, Volume 60, Number 7, July 2008 , pp. 863-870(8)
Publisher: Pharmaceutical Press
Abstract:
To develop a new potent anti-melanogenic agent, we have conjugated lipoic acid (LA) to poly (ethylene) glycol (PEG) of molecular weight 2000 and examined the effects on inhibition of tyrosinase activity and melanin synthesis in B16F10 melanoma cells. The water-soluble LA-PEG 2000 was synthesized from LA and methylated PEG by an esterification reaction in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. Synthetic LA-PEG 2000 was confirmed by IR and 1H-NMR spectroscopy. The new conjugate is a highly water-soluble molecule, which has lower cell cytotoxicity than LA. Treatment with LA-PEG 2000 significantly suppressed the biosynthesis of melanin by up to 63% at 0.25 mM and reduced tyrosinase activity by up to 80% at 0.50 mM in B16F10 melanoma cells. Furthermore, Western blot and RT-PCR studies indicated that treatment with LA-PEG 2000 decreased the level of tyrosinase, which is a melanogenic enzyme. Taken together, these results suggest that LA-PEG 2000 may inhibit melanin biosynthesis by down-regulating levels and expression of tyrosinase activity. Therefore, LA-PEG 2000 can be used effectively as a new agent to inhibit melanogenesis, with lower cytotoxicity than LA (parent molecule) in B16F10 melanoma cells.Document Type: Research article
DOI: 10.1211/jpp.60.7.0007
Affiliations: 1: R&D Center, Hanbul Cosmetics Co. Ltd, 72-7, Yongsung-ri, Samsung-myun, Umsung-kun, Chungbuk 369-834, Korea 2: Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tupper Medical Building, Dalhousie University, 5850 College St., Halifax, Nova Scotia B3H 1X5, Canada

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