N-Phenyl-N'-(2-chloroethyl)ureas (CEUs) as potential antineoplastic agents. Part 3. Role of carbonyl groups in the covalent binding to the colchicine-binding site
In: Bioorganic & medicinal chemistry, Jg. 16 (2008), Heft 3, S. 1206-1217
academicJournal
- print, 33 ref
Zugriff:
In the course of the development of N-phenyl-N'-(2-chloroethyl)ureas (CEUs) as potential antineoplastic agents, we investigated the effect of carbonylated substituting chains of the aromatic ring of CEU on their covalent binding to the colchicine-binding site (C-BS). In this study, we found that CEU, 5e, 5f, 8e, and 8f substituted by either a methyl ester or a methyl ketyl group at the ω-position exhibited a significant antiproliferative activity on HT-29, M21, and MCF-7 tumor cells. SDS-PAGE assays and cell cycle analysis confirmed that 5e, 5f, 8e, and 8f covalently bind to the C-BS and arrest the cell division in G2/M phase. Surprisingly, the presence of ω-carboxyl, ω-ethyl esters or ω-amides decreased significantly both the antiproliferative activity and the specificity toward β-tubulin.
| Titel: |
N-Phenyl-N'-(2-chloroethyl)ureas (CEUs) as potential antineoplastic agents. Part 3. Role of carbonyl groups in the covalent binding to the colchicine-binding site
|
|---|---|
| Autor/in / Beteiligte Person: | MOREAU, Emmanuel ; FORTIN, Sébastien ; LACROIX, Jacques ; PATENAUDE, Alexandre ; ROUSSEAU, Jean L. C ; C-GAUDREAULT, René |
| Link: | |
| Zeitschrift: | Bioorganic & medicinal chemistry, Jg. 16 (2008), Heft 3, S. 1206-1217 |
| Veröffentlichung: | Oxford: Elsevier Science, 2008 |
| Medientyp: | academicJournal |
| Umfang: | print, 33 ref |
| ISSN: | 0968-0896 (print) |
| Schlagwort: |
|
| Sonstiges: |
|