Reduction of 2,3,5-trimethyl-6-(3-pyridylmethyl)-1,4-benzoquinone by PB-3c cells and biological activity of its hydroquinone.
2,3,5-Trimethyl-6-(3-pyridylmethyl)-1,4-benzoquinone (CV-6504) has inhibitory activities on both thromboxane A2 synthase and 5-lipoxygenase as well as scavenging activity against active oxygen species. The latter two activities are closely related to the quinone moiety, which is reduced to a hydroquinone in the living body. Comparison of these two activities for both the quinone and hydroquinone showed that the hydroquinone form had superior activities. Concerning the reduction mechanism by PB-3c cells we can see that superoxide dismutase (SOD) has no influence on the rate of reduction, but dicumarol almost completely inhibits the reduction at a concentration greater than 1 x 10(-6) M. Therefore, it can be concluded that CV-6504 is reduced mainly by two electron donating enzymes without the intermediary of a semiquinone radical and that the resulting hydroquinone inhibits lipid peroxidation as well as 5-lipoxygenase activity.
Ohkawa
S
S
Chemistry Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Terao
T
T
Murakami
M
M
Matsumoto
T
T
Goto
G
G
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D006873:Hydroquinones / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D016859:Lipoxygenase Inhibitors; D010084:Oxidation-Reduction; D051381:Rats; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D016227:Benzoquinones; D006873:Hydroquinones; D016859:Lipoxygenase Inhibitors; C067513:CV 6504; D013930:Thromboxane-A Synthase; C031927:hydroquinone