Abstract: AIMTo study the inhibition of oxygen consumption by annonaceous acetogenins (ACG) and their structure-activity relationship (SAR). METHODSThe inhibition of oxygen consumption in chicken liver cell respiration by different structural ACG was studied by using oxygen electrode technique. RESULTSSix ACG showed potent inhibitory effects like rotenone which was a classical inhibitor of mitochondrial complex I, and was more potent than complex IV inhibitor KCN. The IC₅₀ values of six ACG for inhibiting oxygen consumption suggested that bis-tetrahydrofuran (THF) ACG was 7～11 times more active than non-THF ACG, and A₁-type ACG was more potent than A₂-type ACG. CONCLUSIONThe terminal γ-lactone was crucial for the inhibition of oxygen consumption. The distance between THF and γ-lactone, the hydroxyl groups in the alkyl chain, were the important factors of SAR, but the 4-OH group possibly played some negative role in the exhibit of potent activity.