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Synthesis of Anti‐Microtubule Biaryls and Preliminary Evaluation as Vascular‐Disrupting Agents
Author(s) -
Joncour Agnès,
Liu JianMiao,
Décor Anne,
Thoret Sylviane,
WdzieczakBakala Joanna,
Big Jérôme,
Baudoin Olivier
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800181
Subject(s) - colchicine , microtubule , in vitro , chemistry , endothelial stem cell , cell culture , combinatorial chemistry , small molecule , biochemistry , stereochemistry , microbiology and biotechnology , biology , genetics
Abstract A series of new dibenzoxepines were synthesized in a straightforward and efficient manner through diastereoselective biaryl Suzuki–Miyaura coupling and Brønsted‐acid‐mediated cyclodehydration as key steps. The vascular‐disrupting potential of these molecules was evaluated with various in vitro assays: inhibition of microtubule assembly, antiproliferative activity against cancer cell lines and normal endothelial cells, modification of endothelial cell morphology, and disruption of endothelial cell cords. Two of these compounds showed promising activities in these assays, with profiles similar to that of the reference drug NAC and markedly different from that of colchicine. Altogether, these results show that dibenzoxepines represent promising new leads for the development of more selective vascular‐disrupting agents.