Novel C2-C3' N-peptide linked macrocyclic taxoids. Part 2: synthesis and biological activities of docetaxel analogues with a peptide side chain at C2 and their macrocyclic derivatives.
The synthesis of a series of novel docetaxel analogues possessing a peptide side chain at the C2 position as well as peptide macrocyclic taxoids is described. These compounds were designed to mimic a region of the alpha-tubulin loop equivalent to the paclitaxel binding pocket of beta-tubulin. Fifteen new peptide taxoids were obtained and evaluated as inhibitors of microtubule disassembly as well as cell proliferation. The relationships between these new taxoids and the tau protein motif interacting with microtubules are discussed.
Larroque
Anne-Laure
AL
Institut de Chimie des Substances Naturelles, CNRS, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
Dubois
Joëlle
J
Thoret
Sylviane
S
Aubert
Geneviève
G
Chiaroni
Angèle
A
Guéritte
Françoise
F
Guénard
Daniel
D
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019295:Computational Biology / Q000379:methods; D018360:Crystallography, X-Ray; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D047028:Macrocyclic Compounds; D010455:Peptides; D043823:Taxoids; D000077143:Docetaxel