Synthesis and cytotoxic activity of certain trisubstituted azetidin-2-one derivatives as a cis-restricted combretastatin A-4 analogues
| Autor: | Nadia A. Khalil, Azza T. Taher, Salwa Elmeligie, Ahmed H. El-said |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Double bond Molecular model Cell Survival Stereochemistry 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Bibenzyls Drug Discovery Humans Staudinger reaction chemistry.chemical_classification Combretastatin A-4 Combretastatin biology Cytotoxins 010405 organic chemistry Chemistry Organic Chemistry HCT116 Cells 0104 chemical sciences 030104 developmental biology Tubulin MCF-7 Cells biology.protein Azetidines Molecular Medicine Isomerization Linker |
| Zdroj: | Archives of Pharmacal Research. 40:13-24 |
| ISSN: | 1976-3786 0253-6269 |
| DOI: | 10.1007/s12272-016-0849-y |
| Popis: | Novel series of 1,3,4-trisubstituted azetidin-2-one derivatives 8a-p were synthesized and proposed as cytotoxic agents acting via inhibition of tubulin at the colchicine binding site. The design of the target compounds was based upon modification in the structure of the vascular targeting agent combretastatin A-4 (CA-4). The cis double bond linker in CA-4 was replaced with the azetidin-2-one ring aiming to prevent the cis/trans isomerization that suppresses the activity of CA-4, thereby enhancing its antiproliferative activity. All new compounds were investigated in vitro against MCF-7 and HCT-116 cell lines. The inhibition of tubulin polymerization by four most potent compounds 8g, 8j, 8n and 8o was also evaluated. The synthesis of the final targets was achieved adopting Staudinger reaction. Molecular modeling studies were performed to rationalize the biological results. |
| Databáze: | OpenAIRE |
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