Synthesis and anti-melanogenic effects of lipoic acid-polyethylene glycol ester.
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 (1)H-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.
Kim
Jin-Hwa
JH
R&D Center, Hanbul Cosmetics Co. Ltd, 72-7, Yongsung-ri, Samsung-myun, Umsung-kun, Chungbuk 369-834, Korea.
Sim
Gwan-Sub
GS
Bae
Jun-Tae
JT
Oh
Jung-Young
JY
Lee
Geun-Su
GS
Lee
Dong-Hwan
DH
Lee
Bum-Chun
BC
Pyo
Hyeong-Bae
HB
D000818:Animals; D045744:Cell Line, Tumor; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D004952:Esters; D008543:Melanins; D011092:Polyethylene Glycols; D008063:Thioctic Acid; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase