On the metabolism of quinoline and isoquinoline: possible molecular basis for differences in biological activities

Abstract

Quinoline is a hepatocarcinogen in mice and rats, a mutagen in Salmonella typhimurium, and induces unscheduled DNA synthesis in primary cultures of rat hepatocytes. In contrast, isoquinoline has not been shown to be genotoxic. The metabolites of quinoline and isoquinoline, as formed in vitro with rat liver homogenate, were identified to investigate possible molecular bases for the differences in their biological activity. The ethyl acetate extractable metabolites of quinoline and isoquinoline were analyzed directly by high pressure liquid chromatography and, after silylation, by capillary gas chromatography. The major metabolite of quinoline was 5,6-dihydroxy-5,6-dihydroquinoline. Lesser amounts of 2- and 3-hydroxyquinoline and quinoline-N-oxide were also identified as metabolites. 1-, 4- and 5-Hydroxyiso-quinoline and isoquinoline-N-oxide were detected as metabolites of isoquinoline. 5,6-Dihydroxy-5,6-dihydroiso-quinoline was detected as only a minor metabolite. This difference in the extent to which these isomers are ultimately metabolized to dihydrodiols may be associated with their differences in biological activity. Quinoline, 4-methylquinoline and 7-methylquinoline were bioassayed as tumor initiators on the skin of Sencar mice. While 4-methylquinoline was at least as potent a tumor initiator as quinoline, 7-methylquinoline was not significantly tumorigenic in this assay. These data are consistent with the hypothesis that formation of the 5,6-epoxide of quinoline is associated with its metabolic activation to a tumorigen.

Degradation pathway of quinolines in a biofilm system under denitrifying conditions

“…Further speciation was obtained with a Hewlett Packard 5890 gas chromatograph coupled to a VG 70–250S high‐resolution mass spectrometer (Masslab, U.K.) operated in electron impact ionization mode (75 eV) and by scanning from a mass‐to‐charge ratio ( m/z ) of 50 to 200 in 0.9 s with a resolution of 1,000. Derivatization of extracts with N, O‐bis‐(trimethyl‐silyl)‐trifluoroacetamide in 1% trimethylchlorsilan was done according to LaVole et al [25] for GC‐MS screening.…”

Genotoxicity, carcinogenicity, and mode of action of the fried food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).

“…The N-hydroxy derivative, normally considered more reactive, was less active (28), and thus, the initiating action might stem from ring epoxidation rather than N-oxidation. With quinoline itself, LaVoie et al (29) noted that the 5,6-epoxide is a possible carcinogenic form. In IQ, the imidazole ring occupies the 5,6-region, which may account for the failure of IQ to act as an initiator.…”

A New 1,5‐Dihydroxy‐4‐methoxyisoquinoline from Scolopendra subspinipes mutilans

“…According to previous reports, the main active components of the centipede were polypeptides, histamines, quinolines, and so on . Among numerous biological active ingredients, isoquinoline alkaloid showed the strong pharmacological effects, including anticancer, antimalarial, anti‐inflammatory, antioxidant, antithrombotic, antimicrobial, and other functions …”