Synthesis and biological evaluation of cis-locked vinylogous combretastatin-A4 analogues: derivatives with a cyclopropyl-vinyl or a cyclopropyl-amide bridge.
A series of novel combretastatin A4 analogues, in which the cis-olefinic bridge is replaced by a cyclopropyl-vinyl or a cyclopropyl-amide moiety, were synthesized and evaluated for inhibition of tubulin polymerization and antiproliferative activity. The derivative 9a with a (cis,E)-cyclopropyl-vinyl unit is the most promising compound. As expected, molecular docking of 9a has shown that only one of the cis-cyclopropyl enantiomers is a good ligand for tubulin.
Ty
Nancy
N
Institut Curie, Centre de Recherche, 26 rue d'Ulm, 75248 Paris, France; CNRS, UMR 176, 26 rue d'Ulm, 75248 Paris, France.
Kaffy
Julia
J
Arrault
Alban
A
Thoret
Sylviane
S
Pontikis
Renée
R
Dubois
Joelle
J
Morin-Allory
Luc
L
Florent
Jean-Claude
JC
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D045744:Cell Line, Tumor; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D000577:Amides; D003521:Cyclopropanes; D013267:Stilbenes; D014404:Tubulin; D014753:Vinyl Compounds; C058728:fosbretabulin