Abstract
Quinoline is a chemical with potential pharmaceutical components, such as antimalaria, antiulcer, and antibiotic agents. Quinoline is metabolized by CYP2A6, whose activity is generally shown by coumarin 7-hydroxylation, and the principal product is the 5,6-epoxide of quinoline. We found coumarin 7-hydroxylase activity in bovine liver microsomes and studied the interaction of quinoline and some quinoline derivatives with coumarin 7-hydroxylase activity by fluorometry. Quinoline inhibited coumarin metabolism, and the apparent Vmax value decreased to 0.39 nmol/min/nmol cytochrome P-450 (CYP) in the presence of quinoline from the value (Vmax = 0.63 nmol/min/nmol CYP) in the absence of quinoline. 5-fluoroquinoline (5FQ), 6-fluoroquinoline (6FQ) and 8-fluoroquinoline (8FQ) showed stronger inhibition than quinoline, whereas 3-fluoroquinoline (3FQ) showed weaker inhibition (apparent Vmax was 0.59 nmol/min/nmol CYP). Almost the same inhibition pattern of fluoroquinolines were found in assays of cDNA-expressed human CYP2A6. The results suggest that bovine CYP2A enzymes (s) as well as human CYP2A6 can interact strongly with monofluoroquinolines such as 5-, 6-, and 8-FQ, but weakly with 3-FQ.
