3D QSAR studies of the interaction between β-tubulin and microtubule stabilizing antimitotic agents (MSAA). A combined pharmacophore generation and pseudoreceptor modeling approach applied to taxanes and epothilones

Abstract

Based on the conformer of paclitaxel extracted from the experimental tubulin structure, a pharmacophoric model has been generated and used to find the chemical features common to the taxane and epothilone classes of compounds. This original alignment has been translated into the experimental tubulin binding site obtaining an assembly subsequently submitted to the pseudoreceptor modeling approach. As a result, an original 3D QSAR model, able to evaluate, at a quantitative level, the relationships between the molecular structures and biological data of the studied compounds, has been obtained.