Computer graphics analysis of the interaction of alkoxy methylenedioxybenzenes with cytochromes P4501.

A quantitative structure-activity relationship (QSAR) in a homologous series of alkoxy methylenedioxybenzenes (MDBs) is reported. Measurements of molecular dimensions from computer-generated space-filling structures have provided values for the shape parameter area/depth2. These have been shown to correlate with the extent of inhibition of ethoxyresorufin O-deethylase activity by a series of MDBs. The implication of this is that the MDB nucleus fits the cytochrome P4501 substrate binding site and that this ability decreases with increase in the alkyl chain length of the alkoxy substituent. These findings are in agreement with previous results relating to the spatial dimensions of the cytochrome P4501 binding site, showing that substrate specificity can be rationalized in terms of overall molecular shape.