Tubulin-binding dibenz[c,e]oxepines: Part 2. Structural variation and biological evaluation as tumour vasculature disrupting agents
| Autor: | Timothy W. Wallace, John A. Hadfield, Steven B. Rossington, Kaye J. Williams, Steven D. Shnyder |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Necrosis
Clinical Biochemistry Pharmaceutical Science Tumour vasculature 01 natural sciences Biochemistry Tubulin binding Structural variation Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tubulin Cell Line Tumor Neoplasms Biological property Drug Discovery Journal Article medicine Animals Humans Colchicine Molecular Biology Biological evaluation Dose-Response Relationship Drug Molecular Structure biology 010405 organic chemistry direct arylation Organic Chemistry palladium catalyst 0104 chemical sciences tubulin chemistry Cell culture 030220 oncology & carcinogenesis biology.protein Heterografts Molecular Medicine medicine.symptom Dibenzoxepins |
| Zdroj: | Rossington, S, Hadfield, J, Shnyder, S D, Wallace, T & Williams, K 2017, ' Tubulin-binding dibenz[c,e]oxepines : Part 2. Structural variation and biological evaluation as tumour vasculature disrupting agents ', Bioorganic and Medicinal Chemistry, vol. 25, no. 5, pp. 1630-1642 . https://doi.org/10.1016/j.bmc.2017.01.027 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2017.01.027 |
| Popis: | 5,7-Dihydro-3,9,10,11-tetramethoxybenz[c,e]oxepin-4-ol 1, prepared from a dibenzyl ether precursor via Pd-catalysed intramolecular direct arylation, possesses broad-spectrum in vitro cytotoxicity towards various tumour cell lines, and induces vascular shutdown, necrosis and growth delay in tumour xenografts in mice at sub-toxic doses. The biological properties of 1 and related compounds can be attributed to their ability to inhibit microtubule assembly at the micromolar level, by binding reversibly to the same site of the tubulin αβ-heterodimer as colchicine 2 and the allocolchinol, N-acetylcolchinol 4. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect