Synthesis and inhibitory activity of ubiquinone–acetogenin hybrid inhibitor with bovine mitochondrial complex I

To elucidate the inhibitory action of acetogenins, the most potent inhibitors of mitochondrial complex I, we synthesized an acetogenin analogue which possesses a ubiquinone ring (i.e., the physiological substrate of complex I) in place of the α,β-unsaturated γ-lactone ring of natural acetogenins, and named it Q-acetogenin. Our results indicate that the γ-lactone ring of acetogenins is completely substitutable with the ubiquinone ring. This fact is discussed in light of the inhibitory action of acetogenins.