INHIBITORY EFFECT OF HYDROXYFLAVONES ON THE EXOGENOUS NADH DEHYDROGENASE OF PLANT MITOCHONDRIAL INNER MEMBRANES

The inhibitory properties of a series of 21 flavones were investigated on the uncoupled electron transfer of purified potato tuber mitochondria, with different substrates. Thirteen compounds were shown to be selective inhibitors of the external NADH dehydrogenase of the inner membrane. Among mono- and dihydroxyflavones, some good inhibitors were found, but their efficiency depended greatly on the position of hydroxylation (150 between 20 and 150 μM). For example, 8-hydroxyflavone was six-fold more effective than 5-hydroxyflavone. Except in the case of norwogonin, the aglycones tested were ineffective when they were substituted by more than two hydroxyls, without other substituents. This was the case for quercetin, for example. The best inhibitor of this series was platanetin (I50 = 2 μM). This very lipophilic flavonol (-log P = 5.10) was characterized by the presence of a dimethylallyl chain at the 6-position. When this substituent was replaced by a methyl, (platanin), the effectiveness of the product remained high, but its selectivity was lowered. These results suggest that the value of the lipophilicity parameter (-log P), for the molecules able to attain this target must be between 3.7 and 5.1. However, the lipophilicity parameter on its own does not explain why some flavones act selectively on the external NADH dehydrogenase, probably at the level where the electrons are donated to the quinone pool. © 1990.