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Design, synthesis and anticancer properties of 5-arylbenzoxepins as conformationally restricted iso combretastatin A-4 analogs
- Source :
- European Journal of Medicinal Chemistry, European Journal of Medicinal Chemistry, Elsevier, 2013, 62, pp.28-39. ⟨10.1016/j.ejmech.2012.12.042⟩, European Journal of Medicinal Chemistry, Elsevier, 2013, 62C, pp.28-39. ⟨10.1016/j.ejmech.2012.12.042⟩
- Publication Year :
- 2013
- Publisher :
- HAL CCSD, 2013.
-
Abstract
- International audience; A series of novel benzoxepins 6 was designed and prepared as rigid-isoCA-4 analogues according to a convergent strategy using the coupling of N-tosylhydrazones with aryl iodides under palladium catalysis. The most potent compound 6b, having the greatest resemblance to CA-4 and isoCA-4 displayed antiproliferative activity at nanomolar concentrations against various cancer cell lines and inhibited tubulin assembly at a micromolar range. In addition, benzoxepin 6b led to the arrest of HCT116, K562, H1299 and MDA-MB231 cancer cell lines in the G2/M phase of the cell cycle, and strongly induced apoptosis at low concentrations. Docking studies demonstrated that benzoxepin 6b adopt an orientation similar to that of isoCA-4 at the colchicine binding site on -tubulin.
- Subjects :
- Models, Molecular
Stereochemistry
Cytotoxicity
Apoptosis
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
010402 general chemistry
01 natural sciences
Structure-Activity Relationship
chemistry.chemical_compound
Tubulin
Cell Line, Tumor
Benzoxepin
Stilbenes
Drug Discovery
Benzoxepins
Humans
isoCA-4
Cell Proliferation
Cancer
Pharmacology
Combretastatin
Dose-Response Relationship, Drug
Molecular Structure
biology
010405 organic chemistry
[CHIM.ORGA]Chemical Sciences/Organic chemistry
Aryl
Cell Cycle
Organic Chemistry
General Medicine
Cell cycle
HCT116 Cells
Antineoplastic Agents, Phytogenic
0104 chemical sciences
3. Good health
chemistry
Docking (molecular)
Drug Design
biology.protein
Drug Screening Assays, Antitumor
Subjects
Details
- Language :
- English
- ISSN :
- 02235234 and 17683254
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry, European Journal of Medicinal Chemistry, Elsevier, 2013, 62, pp.28-39. ⟨10.1016/j.ejmech.2012.12.042⟩, European Journal of Medicinal Chemistry, Elsevier, 2013, 62C, pp.28-39. ⟨10.1016/j.ejmech.2012.12.042⟩
- Accession number :
- edsair.doi.dedup.....15870801f79d25760e53286daf16dc98