New quinoline compounds were designed, synthesized, and examined with submitochondria. Most compounds showed high activity against NADH-ubiquinone oxidoreductase. Inhibition activity was mainly affected by the length of the lipophilic part, regardless of bulkiness or location of a phenyl group in the side chain. The $eta-methyl$ group was demons)rated to be the optimal functionality on the nuclei of the quinoline derivatives so 4hat either deletion or insertion of a methylene on the group eliminated its activity.