[Inhibition of oxygen consumption by annonaceous acetogenins in liver cell respiration and their structure-activity relationship].
OBJECTIVE
To study the inhibition of oxygen consumption by annonaceous acetogenins (ACG) and their structure-activity relationship (SAR).


METHODS
The inhibition of oxygen consumption in chicken liver cell respiration by different structural ACG was studied by using oxygen electrode technique.


RESULTS
Six 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 bistetrahydrofuran (THF) ACG was 7-11 times more active than non-THF ACG, and A1-type ACG was more potent than A2-type ACG.


CONCLUSIONS
The terminal gamma-lactone was crucial for the inhibition of oxygen consumption. The distance between THF and gamma-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.
Xu
Zhi-Fang
ZF
South China Institute of Botany, Chinese Academy of Sciences, Guangzhou 510650, China. xuzf@scib.ac.cn
Wei
Xiao-yi
XY
Xie
Hai-hui
HH
Yang
Ren-zhou
RZ
D054378:Acetogenins; D000818:Animals; D031041:Annona / Q000737:chemistry; D002469:Cell Separation; D002645:Chickens; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008099:Liver / Q000166:cytology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010946:Plants, Medicinal / Q000737:chemistry; D012639:Seeds / Q000737:chemistry; D013329:Structure-Activity Relationship
D054378:Acetogenins; D005233:Fatty Alcohols; D005663:Furans; D007783:Lactones; C061022:bullatacin; C059660:squamocin