Synthesis and characterization of Δlac-acetogenins that potently inhibit mitochondrial complex I

Four Δlac-acetogenins have been prepared and characterized as inhibitors of the mitochondrial respiratory chain, to define the effects of unsaturation within the alkyl substituents. In keeping with earlier reports, the presence of acetylenic functionalities within the alkyl substituents slightly diminished their potency of inhibition of NADH oxidase activity, which measures the overall transfer of electrons from NADH to oxygen through mitochondrial complexes I, III, and IV. In contrast, both of the acetylenic Δlac-acetogenins were far more active in a NADH–ubiquinone Q1 oxidoreductase assay that measures complex I function per se.

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