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ID: ALA1137485
Journal: Bioorg Med Chem Lett
Title: Design, synthesis, and biological testing of pyrazoline derivatives of combretastatin-A4.
Authors: Johnson M, Younglove B, Lee L, LeBlanc R, Holt H, Hills P, Mackay H, Brown T, Mooberry SL, Lee M.
Abstract: 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).
CiteXplore: 17827004