The acridones, new inhibitors of mitochondrial NADH: ubiquinone oxidoreductase (complex I).
Acridones (9-azaanthracen-10-ones) were found to be powerful inhibitors of mitochondrial NADH: ubiquinone oxidoreductase. Their inhibitory activity was best if an alkyl or alkyloxy substituent resided in the 4-position. Biological activity reached a maximum at a chain length of 9-10 A. Halogen substitution in position 7, but not in positions 6 and 7, further enhanced activity. 2-Alkylacridones were much less active. Inhibitory activity in a Quantitative Structure-Activity Relationship (QSAR) could be correlated to Verloop's STERIMOL parameters L and L2 (Verloop, A., Hoogenstraten, W. and Tipker, J. (1976) in Drug Design (Ariens, E.J., ed.), Vol. 7, pp. 165-207, Academic Press, New York). The QSAR could be further improved by inclusion of the lipophilicity parameter pi.
Oettmeier
W
W
Lehrstuhl Biochemie der Pflanzen, Ruhr-Universität, Bochum, Germany.
Masson
K
K
Soll
M
M
D000166:Acridines / Q000494:pharmacology*; D054831:Acridones; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D007700:Kinetics; D008929:Mitochondria, Heart / Q000201:enzymology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000166:Acridines; D054831:Acridones; C041300:acridone; D016660:NAD(P)H Dehydrogenase (Quinone)