Novel C2-C3' N-peptide linked macrocyclic taxoids. Part 1: Synthesis and biological activities of docetaxel analogues with a peptide side chain at C3'

Anne-Laure Larroque; Joëlle Dubois; Sylviane Thoret; Geneviève Aubert; Daniel Guénard; Françoise Guéritte

doi:10.1016/j.bmcl.2005.07.069

Novel C2-C3' N-peptide linked macrocyclic taxoids. Part 1: Synthesis and biological activities of docetaxel analogues with a peptide side chain at C3'

Bioorg Med Chem Lett. 2005 Nov 1;15(21):4722-6. doi: 10.1016/j.bmcl.2005.07.069.

Authors

Anne-Laure Larroque¹, Joëlle Dubois, Sylviane Thoret, Geneviève Aubert, Daniel Guénard, Françoise Guéritte

Affiliation

¹ Institut de Chimie des Substanes Naturelles, CNRS, 1 avenue de la Terrasse, 91198 Gif sur Yvette Cedex, France.

PMID: 16165352
DOI: 10.1016/j.bmcl.2005.07.069

Abstract

A series of novel docetaxel analogues possessing a peptide side chain at the C3'-N position was synthesized. These compounds were designed to mimic a region of the alpha-tubulin loop that is equivalent to the paclitaxel binding pocket in beta-tubulin. Eight new peptidic taxoids were obtained and evaluated as inhibitors of microtubule disassembly, as well as for their cytotoxicity.

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Binding Sites
Cell Proliferation / drug effects
Docetaxel
Inhibitory Concentration 50
Macrocyclic Compounds / chemical synthesis
Macrocyclic Compounds / chemistry
Macrocyclic Compounds / pharmacology
Models, Molecular
Molecular Structure
Peptides
Protein Binding
Rats
Structure-Activity Relationship
Taxoids / chemical synthesis*
Taxoids / chemistry
Taxoids / pharmacology
Tubulin / chemistry
Tubulin / drug effects

Substances

Antineoplastic Agents
Macrocyclic Compounds
Peptides
Taxoids
Tubulin
Docetaxel