title: 3D QSAR models of interactions between beta-tubulin and microtubule stabilizing antimitotic agents (MSAA): a survey on taxanes and epothilones.
abstract: In the last two decades, paclitaxel (Taxol), 1) has dominated the anticancer chemotherapy as one of the most important antimitotic agents. Despite its clinical success, it presents some limitations due to its low aqueous solubility or multidrug-resistance (MDR) susceptibility. Among new compounds sharing paclitaxel's mechanism of action, epothilones have emerged as very promising candidates and are currently under clinical trials. While the electron crystallography (EC) structure of tubulin with embedded paclitaxel is available, only hypotheses about epothilone binding upon the protein may be advanced. This review illustrates our efforts in the minireceptor modeling approach as the most recent advances in the field of three-dimensional quantitative structure-activity relationship (3D QSAR) studies involving taxanes, epothilones and the corresponding protein environment.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Aldo Moro, I-53100 Siena, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manetti
authors.forename: Laura
authors.initials: L
authors.lastname: Maccari
authors.forename: Federico
authors.initials: F
authors.lastname: Corelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000737:chemistry* / Q000494:pharmacology; D034261:Epothilones / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D034261:Epothilones; D043823:Taxoids; D014404:Tubulin; C080625:taxane