Design of novel hybrid vitamin C derivatives: thermal stability and biological activity.
Novel hybrid L-ascorbic acid (vitamin C) derivatives with other biologically active substances, 5-hydroxy-2-hydroxymethyl-beta-pyrone (kojic acid) and alpha-tocopherol (vitamin E), linked at the C-2 or C-3 hydroxyl group were synthesized, and their thermal stability and inhibitory effects on tyrosinase activity, active oxygen species (AOS), and free radicals were estimated in vitro. It was found that a hydrophilic derivative, 2-O-(5-hydroxy-4H-pyran-4-one-2-methyl)-L-ascorbic acid (1), exhibited good thermal stability and inhibitory activities against tyrosinase catalyzed melanin formation, AOS, and free radicals compared to vitamin C and its conventional derivatives (such as the 2-phosphate 6-stearate and 2.6-dipalmitate, and 2-O-octadecylascorbic acid), as well as vitamin E, kojic acid, and arbutin. It is apparent that 1 has the biological properties of vitamin C and kojic acid, and acts synergistically. The hydroxyl groups at the C-3 position of the vitamin C moiety and the C-5 position of the kojic acid moiety are critical for the biological activities. We consider that the kojic acid moiety of 1 counterbalances the diminution of the biological activity due to shielding of the biologically important C-2 hydroxyl group of the vitamin C moiety. In addition, the thermal stability was significantly improved relative to not only vitamin C but also kojic acid. Further, a lipophilic derivative, 3-O-[(alpha-tocopheryloxy)-2-hydroxypropyl]-L-ascorbic acid, 2, was far more stable than vitamin C and its typical lipophilic derivatives. Compound 2 exhibited almost the same inhibitory activities against tyrosinase-catalyzed melanin formation, AOS, and free radicals as typical lipophilic derivatives, although these biological activities of 2 were lower than those of vitamin C.
Morisaki
K
K
Department of Applied Chemistry, Faculty of Engineering, Ehime University, Matsuyama, Japan.
Ozaki
S
S
D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015764:Bepridil / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000737:chemistry; D001713:Biphenyl Compounds; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000737:chemistry; D008543:Melanins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D010777:Photochemistry; D010851:Picrates; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000737:chemistry; D013696:Temperature; D014443:Tyrosine / Q000037:antagonists & inhibitors / Q000737:chemistry; D014810:Vitamin E / Q000737:chemistry / Q000494:pharmacology
C104605:2-O-(5-hydroxy-4H-pyran-4-one-2-methyl)ascorbic acid; C104604:3-O-((tocopheryloxy)-2-hydroxypropyl)ascorbic acid; D001713:Biphenyl Compounds; D005609:Free Radicals; D008543:Melanins; D010851:Picrates; D011753:Pyrones; D017382:Reactive Oxygen Species; D013481:Superoxides; D014810:Vitamin E; D014443:Tyrosine; C011890:kojic acid; D015764:Bepridil; C004931:1,1-diphenyl-2-picrylhydrazyl; D014442:Monophenol Monooxygenase; D001205:Ascorbic Acid