Design, synthesis, and biological testing of pyrazoline derivatives of combretastatin-A4
| Autor: | Herman L. Holt, Toni Brown, Lauren Lee, Brent Younglove, Hilary Mackay, Regan M. LeBlanc, Marlie A. Johnson, Moses Lee, Susan L. Mooberry, Patrice Hills |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Molecular model Stereochemistry Dimer Organic Chemistry Clinical Biochemistry Pharmaceutical Science Pyrazoline Biochemistry Chemical synthesis In vitro Cell Line chemistry.chemical_compound Mice chemistry Acetylation Drug Design Drug Discovery Stilbenes Molecular Medicine Animals Pyrazoles Cytotoxicity Molecular Biology Derivative (chemistry) |
| Zdroj: | Bioorganicmedicinal chemistry letters. 17(21) |
| ISSN: | 0960-894X |
| Popis: | Fourteen N-acetylated and non-acetylated 3,4,5-tri- or 2,5-dimethoxypyrazoline analogs of combretastatin-A4 (1) were synthesized. A non-acetylated derivative (5a) with the same substituents as CA-4 (1) was the most active compound in the series, with IC(50) values of 2.1 and 0.5 microM in B16 and L1210 cell lines, respectively. In contrast, a similar compound with an acetyl group at N1 of the pyrazoline ring (6g) showed poor activity in the cell lines studied. A cell-based assay indicated that compound 5a caused extensive microtubule depolymerization with an EC(50) value of 7.1 microM in A-10 cells while no activity was seen with the acetylated compound. Molecular modeling studies showed that these compounds possess a twisted conformation similar to CA-4 (1). |
| Databáze: | OpenAIRE |
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