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6-Methylhydroxylation of the anti-cancer agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by flavin-containing monooxygenase 3


, : 6-Methylhydroxylation of the anti-cancer agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by flavin-containing monooxygenase 3. European Journal of Drug Metabolism and Pharmacokinetics 27(3): 179-183

The involvement of flavin-containing monooxygenase (FMO) in the 6-methylhydroxylation of the experimental anti-cancer drug 5,6-dimethylxanthenone-4-acetic acid (DMXAA) was investigated by use of human liver microsomes and microsomes containing cDNA-expressed FMOs. The involvement of FMO in the formation of 6-methyl hydroxylate of DMXAA, 6-hydroxymethyl-5-methylxanthenone-4-acetic acid (6-OH-MXAA) in human liver microsomes was indicated by the fact that this biotransformation was sensitive to heat treatment, increased at pH 8.3, and inhibited by methimazole. Only FMO3 formed 6-OH-MXAA at a similar rate to that in cDNA-expressed cytochromes P-450 (CYP)1A2. The results of this study indicate that human FMO3 has the capacity to form 6-OH-MXAA, but plays a lesser important role for this reaction than CYP1A2 that has been demonstrated to catalyse 6-OH-MXAA formation.

US$19.90

PMID: 12365199

DOI: 10.1007/bf03190455


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