3D QSAR studies of the interaction between beta-tubulin and microtubule stabilizing antimitotic agents (MSAA). A combined pharmacophore generation and pseudoreceptor modeling approach applied to taxanes and epothilones.
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.
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Aldo Moro, I-53100 Siena, Italy.
Fabrizio
F
Manetti
Stefano
S
Forli
Laura
L
Maccari
Federico
F
Corelli
Maurizio
M
Botta
D000970:Antineoplastic Agents / Q000737:chemistry*; D034261:Epothilones / Q000737:chemistry*; D008870:Microtubules; D008956:Models, Chemical; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry*; D014404:Tubulin / Q000737:chemistry*
D000970:Antineoplastic Agents; D034261:Epothilones; D043823:Taxoids; D014404:Tubulin