The Identification of De-Alkylation Reactions Catalysed by Cytochrome P450 using Pharmacophore Three-dimensional Structure

Abstract

Quantitative structure activity relationships (QSAR) and pharmacophore three-dimensional structure modelling provide possible methods for understanding the first pass metabolism of human cytochrome P450 substrates in the absence of reliable crystal structures of the human enzymes. The increasing need for alternative and objective methods of metabolism prediction has developed into computational approaches to the problem of understanding the enzyme and substrate behaviour. By analysis of the three-dimensional structure known to be catalysed by human P450 and comparison to other substrates involved in similar alkyl removal reactions, along with the alignment of molecular interaction potentials (MIP), a common template for specific dealkylations is proposed.