Synthesis of new antioxidant conjugates and their in vitro hydrolysis with Stratum corneum enzymes.
The aim of this study was to synthesize new precursors, combinations of well-known antioxidant molecules: resveratrol, lipoic acid and vitamin E to improve their photo-stability and to modulate their lipophylic character. Active antioxidants are available through a controlled release by the action of skin enzymes upon a topic application. Two conjugates are described, the combinations of resveratrol-lipoic acid (6) and resveratrol-vitamin E (10). Both compounds are new molecules. This work describes their synthesis, characterization, stability study and in vitro biohydrolysis. Stratum corneum enzymes efficiently hydrolysed in vitro precursor 6 and liberate both active molecules, resveratrol and lipoic acid over the period of 72 h. Precursor 10 was hydrolysed in vitro by combination of Stratum corneum enzymes and the cholesterol esterase. A simple technique of preparation of the human Stratum corneum hydrolases is also described.
Gelo-Pujic
M
M
Rhodia CRTL, 85 rue des frères Perret, 69192 Saint Fons cedex, France. mirjana.gelo-pujic@eu.rhodia.com
Desmurs
J-R
JR
Kassem
T
T
Delaire
S
S
Adao
A
A
Tawil
D
D
D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D004355:Drug Stability; D004950:Esterases / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D000077185:Resveratrol; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D017550:Spectroscopy, Fourier Transform Infrared; D002787:Sterol Esterase / Q000378:metabolism; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry*; D008063:Thioctic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D024502:alpha-Tocopherol / Q000138:chemical synthesis / Q000737:chemistry*
D000975:Antioxidants; D013267:Stilbenes; D008063:Thioctic Acid; D004950:Esterases; D002787:Sterol Esterase; D024502:alpha-Tocopherol; D000077185:Resveratrol