Radical intensity and carcinogenic activity of benz[c]acridines.
Among 13 benz[c]acridines, six 7-methyl-substituted compounds (7-methylbenz[c]acridine, 7,9-dimethylbenz[c]acridine, 7,10-dimethylbenz[c]acridine, 7,11-dimethylbenz[c]acridine, 7,9,10-trimethylbenz[c]acridine, 7,9,11-trimethylbenz[c]acridine) were carcinogenic, while the other seven compounds (benz[c] acridine, 8-methylbenz[c]acridine, 9-methylbenz[c]acridine, 10-methylbenz[c]acridine, 11-methylbenz[c]acridine, 5,7-dimethylbenz[c]acridine, cis-5,6-dihydroxy-5,6-dihydrobenz[c]acridine) were inactive. Using both McLachlan-Hückel molecular orbital (McLachlan-HMO) and HMO methods, all the carcinogenic compounds were shown to have the elevated pi-spin density at 12th nitrogen atom of their molecules, as compared with noncarcinogenic compounds. Electron spin resonance (ESR) spectroscopy, however, revealed that both carcinogenic and noncarcinogenic compounds produced no detectable amounts of radical. This is in contrast to ascorbates, gallates and benzo[a]phenothiazines, which induced apoptosis by radical mediated mechanism(s). Amino acid analysis demonstrated that methionine oxidation is not involved in the induction of carcinogenic activity by benz[c]acridines.
Satoh
K
K
Analysis Center, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Sakagami
H
H
Kadofuku
T
T
Kurihara
T
T
Motohashi
N
N
D000166:Acridines / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000031:analogs & derivatives; D001597:Benzylidene Compounds; D002273:Carcinogens; D002454:Cell Differentiation / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D008715:Methionine / Q000737:chemistry; D010084:Oxidation-Reduction
D000166:Acridines; D001597:Benzylidene Compounds; D002273:Carcinogens; D005609:Free Radicals; D008715:Methionine; C035985:benz(c)acridine; D001205:Ascorbic Acid; C070680:zilascorb