Computational comparison of microtubule-stabilising agents laulimalide and peloruside with taxol and colchicine

• Published in: Bioorganic & medicinal chemistry letters 2004-10, Vol.14 (19), p.4825-4829
• Main Authors: Pineda, Oriol, Farràs, Jaume, Maccari, Laura, Manetti, Fabrizio, Botta, Maurizio, Vilarrasa, Jaume
• Format: Article
• Language: English
• Subjects: Anti-cancer drugs; Antineoplastic agents; Binding Sites; Biological and medical sciences; Bridged Bicyclo Compounds, Heterocyclic - chemistry; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Colchicine - chemistry; Colchicine - pharmacology; Docking; General aspects; Lactones - chemistry; Lactones - pharmacology; Laulimalide; Macrolides; Medical sciences; Microtubules - drug effects; Modelling; Paclitaxel - chemistry; Paclitaxel - pharmacology; Peloruside; Pharmacology. Drug treatments; Protein Conformation; Quantitative Structure-Activity Relationship; Taxoids - chemistry; Taxoids - pharmacology; Tubulin - chemistry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.07.053

Microtubule-stabilising agents laulimalide and peloruside have been compared with tubulin-interacting drugs paclitaxel and colchicine by different computational approaches. Docking and QSAR-based programs point to a favourable interaction with the β tubulin paclitaxel binding site, although an additional, preferred binding site has been found at the α subunit of tubulin. All together provides a plausible rationalisation of the singular binding features of these microtubule stabilisers and paves the way for future structural studies. ▪ Microtubule-stabilising agents laulimalide and peloruside have been compared with tubulin-interacting drugs paclitaxel and colchicine by different computational approaches. Docking and QSAR-based programs point to a favourable interaction with the β tubulin paclitaxel binding site, although an additional, preferred binding site has been found at the α subunit of tubulin. All together provides a plausible rationalisation of the singular binding features of these microtubule stabilisers and paves the way for future structural studies.