A QSAR FOR STEROIDAL COMPOUND INTERACTION WITH CYTOCHROME P4501A1

摘要

The well-known binding and metabolism of polycyclic aromatic hydrocarbons (PAHs) by cytochrome P4501A1 has led to a proposed metabolic specialization of P4501A1 to endogenous hormones. To assess this hypothesis, the binding affinities of nine steroidal molecules of increasing multiple bond content and the aromatic compound chrysene were tested against a standard ethoxyresorufin O-deethylation assay. Both the hydrophobicity and the planarity of these molecules correlate to their binding efficiency. However, the product of these two properties shows a much stronger correlation than each separately. By using standard mathematical identities, hydrophobicity and planarity can be related to the enthalpy and entropy of activation, respectively. In this model, the hydrophobicity represents the adhesiveness per unit contact area with the active site, and the planarity the proportion of molecular structures in contact with the site. The net adhesiveness is therefore accidentally largest for the xenobiotic PAH structures.