Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus, Staphylococcus epidermidisand human cells

Table 7 Effects on human cytochrome P450 function in vitro

Cytochrome enzyme	Percentage of control activity
	1 μM IQ-143	10 μM IQ-143	100 μM IQ-143
1A2	106.9	127.3	126.2
2C8	142.8	144.0	146.0
2C9	122.7	130.0	142.0
2C19	102.2	101.8	90.1
2D6	99.1	100.9	58.7
3A4	98.6	95.3	6.6

CYP enzymes derived from baculovirus-infected insect cells were incubated with the corresponding substrates and IQ-143 at concentrations of 1 μM, 10 μM, and 100 μM as described by Unger and Frank [34]. As shown here (and in Figure S3), only very high doses of IQ-143 reduced the activity of the CYP isoenzymes 2C19, 2D6, and 3A4. At concentrations below 100 μM IQ-143, the activities were even higher compared to those of the control group.

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