Novel C2-C3' N-peptide linked macrocyclic taxoids. Part 1: Synthesis and biological activities of docetaxel analogues with a peptide side chain at C3'.
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.
Larroque
Anne-Laure
AL
Institut de Chimie des Substanes Naturelles, CNRS, 1 avenue de la Terrasse, 91198 Gif sur Yvette Cedex, France.
Dubois
Joëlle
J
Thoret
Sylviane
S
Aubert
Geneviève
G
Guénard
Daniel
D
Guéritte
Françoise
F
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D020128:Inhibitory Concentration 50; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects
D000970:Antineoplastic Agents; D047028:Macrocyclic Compounds; D010455:Peptides; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel