Synthesis and inhibitory activity of new ethylenedioxyquinones as analogs of coenzyme

Article abstract of DOI:10.1021/jm00267a007

A new series of analogs of coenzyme Q, 2,3 ethylenedioxy 5 hydroxy 6 alkyl 1,4 benzoquinones, was synthesized on the basis of the minor differences in the electronic and rotational nature between the 2,3 ethylenedioxy group and 2,3 dimethoxy groups. These differences could affect the redox potential of the 1,4 benzoquinone and, in turn, affect inhibitory activity. The 6 alkyl groups were farnesyl, phytyl, nonyl, decyl, pentadecyl, heptadecyl, and 5' (cyclohexyl)pentyl. The succinoxidase and DPNH oxidase systems of intact mitochondria from beef heart were used in tests for inhibition. The nonyl, decyl, pentadecyl, and farnesyl analogs showed inhibitions of less than 40%; and the phytyl, heptadecyl, and 5' (cyclohexyl)pentyl analogs showed inhibitions of about 50% in succinoxidase. All the analogs were less inhibitory in DPNH oxidase. 2,3 Dimethoxy 5 hydroxy 6 n pentadecyl 1,4 benzoquinone showed 91% inhibition at a concentration of 97 nmol of inhibitor/mg of mitochondrial protein, while 2,3 ethylenedioxy 5 hydroxy 6 n pentadecyl 1,4 benzoquinone exhibited only 37% inhibition at the higher concentration of 140 nmol of inhibitor/mg of mitochondrial protein in the succinoxidase system. Similarly, this 2,3 dimethoxyquinone was a more potent inhibitor in DPNH oxidase. 2,3 Dimethoxy 5 hydroxy 6 n pentadecyl 1,4 benzoquinone showed 91% inhibition at a concentration of 97 nmol of inhibitor/mg of mitochondrial protein, while 2,3 ethylenedioxy 5 hydroxy 6 n pentadecyl 1,4 benzoquinone exhibited only 37% inhibition at the higher concentration of 140 nmol of inhibitor/mg of mitochondrial protein in the succinoxidase system. Similarly, this 2,3 dimethoxyquinone was a more potent inhibitor in DPNH oxidase than the corresponding 2,3 ethylenedioxyquinone. Apparently, 2,3 dimethoxy groups are more favorable than the 2,3 ethylenedioxy group on the 5 hydroxy 6 alkyl 1,4 benzoquinone nucleus for inhibition of these two CoQ oxidases.