Action of the novel antioxidants 4GBE43 and 2BBE43 against lipid peroxidation.
The action and the effect of the newly synthesized compounds 4GBE43 [N-(1,2-diethyltetrahydro-1H-pyrazol-4-yl)-4-[(2E)-3,7-diethyl-2,6-octadienyl] oxybenzamide] and 2BBE43 [2-(benzyloxy)-N-(1,2-diethyltetrahydro-1H-pyrazol-4-yl)benzamide] against lipid peroxidation were studied. 4GBE43 and 2BBE43 quenched the ESR signal of diphenylpicrylhydrazyl (DPPH), suggesting that 4GBE43 and 2BBE43 act as scavengers of free radicals and that each compound quenched 6 free radical molecules. These compounds suppressed the oxidation of methyl linoleate emulsions and soybean phosphatidylcholine liposomes by a free radical initiator, suggesting that these compounds quench the lipid peroxyl radical. 4GBE43 and 2BBE43 also suppressed the spontaneous oxidation of rat brain homogenates. The inhibitory effect of 2BBE43 was of the same order of magnitude (IC50) as that of probucol. The IC50 of 4GBE43 was on the same order of magnitude as that of alpha-tocopherol. However, 4GBE43 at 10(-4)-10(-5) M completely inhibited peroxidation, showing it to be more effective than alpha-tocopherol. These results suggest that 4GBE43 and 2BBE43 act as antioxidants by quenching the lipid peroxyl radical.
Ezure
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Shiseido Pharmaceutical Research Laboratories, 2-12-1 Fukuura, Kanazawa-ku, 236-8643, Yokohama, Kanagawa, Japan. tomonobu.ezure@to.shiseido.co.jp
Kanayama
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Nishino
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008041:Linoleic Acids / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats
C430683:2-(benzyloxy)-N-(1,2-diethyltetrahydro-1H-pyrazol-4-yl)benzamide; D000975:Antioxidants; D001549:Benzamides; D008041:Linoleic Acids; D008081:Liposomes; C430684:N-(1,2-diethyltetrahydro-1H-pyrazol-4-yl)-4-3,7-diethyl-2,6-octadienyl oxybenzamide; D011720:Pyrazoles; C005575:methyl linoleate