Inhibitors of CYP6D1 in house fly microsomes

CYP6D1 is a cytochrome P450 responsible for the metabolism of insecticides and other xenobiotics in the house fly (Musca domestica). Using a CYP6D1-specific monooxygenase activity and a non-CYP6D1-specific monooxygenase activity, 21 compounds were evaluated as inhibitors of CYP6D1 in house fly microsomes. CYP6D1 was strongly inhibited by xanthotoxin, chlorpyrifos, beta-naphthoflavone, piperonyl butoxide and 5-methoxypsoralen. The highest selectivity for inhibition of CYP6D1 was seen for 5-methoxypsoralen, xanthotoxin, beta-naphthoflavone, chlorpyrifos oxon, isosafrole and psoralen. The results clearly indicate that identification of isoform-selective inhibitors of P450s within an insect, and across species, is possible. In addition, psoralen and 5-methoxypsoralen stimulated ethoxycoumarin O-deethylation suggesting that these compounds were substrates for monooxygenases in house fly microsomes. Isosafrole was shown to be a potent synergist of pyrethroid insecticides in adult house flies.