Biological activity of novel synthetic derivatives of carnosine.
Two novel derivatives of carnosine--(S)-trolox-L-carnosine (STC) and (R)-trolox-L-carnosine (RTC) are characterized in terms of their antioxidant and membrane-stabilizing activities as well as their resistance to serum carnosinase. STC and RTC were synthesized by N-acylation of L-carnosine with (S)- and (R)-trolox, respectively. STC and RTC were found to react more efficiently with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and protect serum lipoproteins from Fe(2+)-induced oxidation more successfully than carnosine and trolox. At the same time, STC, RTC and trolox suppressed oxidative hemolysis of red blood cells (RBC) less efficiently than carnosine taken in the same concentration. When oxidative stress was induced in suspension of cerebellum granule cells by their incubation with N-methyl-D-aspartate (NMDA), or hydrogen peroxide (H(2)O(2)), both STC and RTC more efficiently decreased accumulation of reactive oxygen species (ROS) than carnosine and trolox. Both STC and RTC were resistant toward hydrolytic degradation by human serum carnosinase. STC and RTC were concluded to demonstrate higher antioxidant capacity and better ability to prevent cerebellar neurons from ROS accumulation than their precursors, carnosine and trolox.
Stvolinsky
S L
SL
Laboratory of Neurochemistry, Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, 125367, Russia. slstvolinsky@mail.ru
Bulygina
E R
ER
Fedorova
T N
TN
Meguro
K
K
Sato
T
T
Tyulina
O V
OV
Abe
H
H
Boldyrev
A A
AA
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000737:chemistry; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002336:Carnosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000187:drug effects / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D004150:Dipeptidases / Q000378:metabolism / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007501:Iron / Q000037:antagonists & inhibitors; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D015394:Molecular Structure; D016202:N-Methylaspartate / Q000633:toxicity; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010851:Picrates / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D001713:Biphenyl Compounds; D002839:Chromans; D016877:Oxidants; D010851:Picrates; D017382:Reactive Oxygen Species; C550427:trolox-L-carnosine; D016202:N-Methylaspartate; D002336:Carnosine; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D007501:Iron; C522928:CNDP1 protein, human; D004150:Dipeptidases; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid