| Autor: |
Alloatti D; R&D, Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Via Pontina Km 30.400, 00040 Pomezia, Italy., Giannini G, Cabri W, Lustrati I, Marzi M, Ciacci A, Gallo G, Tinti MO, Marcellini M, Riccioni T, Guglielmi MB, Carminati P, Pisano C |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2008 May 08; Vol. 51 (9), pp. 2708-21. Date of Electronic Publication: 2008 Apr 09. |
| DOI: |
10.1021/jm701362m |
| Abstrakt: |
With the aim of understanding the influence of fluorine on the double bond of the cis-stilbene moiety of combretastatin derivatives and encouraged by a preliminary molecular modeling study showing a different biological environment on the interaction site with tubulin, we prepared, through various synthetic approaches, a small library of compounds in which one or both of the olefinic hydrogens were replaced with fluorine. X-ray analysis on the difluoro-CA-4 analogue demonstrated that the spatial arrangement of the molecule was not modified, compared to its nonfluorinated counterpart. SAR analysis confirmed the importance of the cis-stereochemistry of the stilbene scaffold. Nevertheless, some unpredicted results were observed on a few trans-fluorinated derivatives. The position of a fluorine atom on the double bond may affect the inhibition of tubulin polymerization and cytotoxic activity of these compounds. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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