Lead identification of conformationally restricted benzoxepin type combretastatin analogs : synthesis, antiproliferative activity, and tubulin effects
| Autor: | Irene Barrett, David Lloyd, Mary J. Meegan, Andrew J. S. Knox, Lisa M. Greene, Miriam Carr, Daniela M. Zisterer, Niamh M. O’Boyle |
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| Přispěvatelé: | Barrett, I, Carr, M, O'Boyle, NM, Greene, LM, Knox, AJS, Lloyd, David George, Zisterer, DM, Meegan, MJ |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular antiproliferative activity Stereochemistry Breast Neoplasms chemistry.chemical_compound Structure-Activity Relationship Breast cancer cell line Tubulin Benzoxepin Carcinoma Cell Cell Line Tumor Drug Discovery Stilbenes benzoxepin combretastatin analogs Benzoxepins Humans skin and connective tissue diseases Cell Proliferation Pharmacology Combretastatin Binding Sites biology Molecular Structure Chemistry General Medicine Antineoplastic Agents Phytogenic Drug Design biology.protein Female Human breast Protein Binding |
| Popis: | We have synthesized a series of polymethoxylated rigid analogs of combretastatin A-4 which contain a benzoxepin ring in place of the usual ethylene bridge present in the natural combretastatin products. The compounds display antiproliferative activity when evaluated against the MCF-7 and MDA human breast carcinoma cell lines. 5-(3-Hydroxy-4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-2,3-dihydro-benzoxepine (11g) was found to be the most potent product when evaluated against the MCF-7 breast cancer cell line. A brief computational study of the structure-activity relationship for the synthesized compounds is presented. These 4,5-diarylbenzoxepins are identified as potentially useful scaffolds for the further development of antitumor agents which target tubulin. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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