Isocombretastatins a versus combretastatins a: the forgotten isoCA-4 isomer as a highly promising cytotoxic and antitubulin agent.
Herein is reported a convergent synthesis of isocombretastatins A, a novel class of potent antitubulin agents. These compounds having a 1,1-diarylethylene scaffold constitute the simplest isomers of natural Z-combretastatins A that are easy to synthesize without need to control the Z-olefin geometry. The discovery of isoCA-4 with biological activities comparable to that of CA-4 represents a major progress in this field.
Messaoudi
Samir
S
Laboratoire de Chimie Therapeutique, Faculte de Pharmacie, Univ Paris-Sud, CNRS, BioCIS-UMR 8076, Clement, Chatenay-Malabry F-92296, France.
Tréguier
Bret
B
Hamze
Abdallah
A
Provot
Olivier
O
Peyrat
Jean-François
JF
De Losada
Jordi Rodrigo
JR
Liu
Jian-Miao
JM
Bignon
Jérôme
J
Wdzieczak-Bakala
Joanna
J
Thoret
Sylviane
S
Dubois
Joëlle
J
Brion
Jean-Daniel
JD
Alami
Mouâd
M
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001632:Bibenzyls / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002733:Chlorophenols / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D050257:Tubulin Modulators / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001632:Bibenzyls; D002733:Chlorophenols; D010456:Peptides, Cyclic; D050257:Tubulin Modulators; C023490:complestatin; C040105:combretastatin