A Stereospecific Route for the Preparation of trans-Combretastatin Analogs: Synthesis and Cytotoxicity
Pati, H. N.; Taherbhai, Z. T.; Forrest, L.; Wicks, M.; Bailey, S. L.; Staples, A.; Stewart, M.; Pennington, W. T.; Harris, J. L.; Lee, M. A Stereospecific Route for the Preparation of trans-Combretastatin Analogs: Synthesis and Cytotoxicity. Lett. Drug Des. Discovery 2004, 1, 275-278.
The stereospecific synthesis of nine trans-combretastatin analogs (5 - 13) is described. The trans geometry of these products was ascertained by the vinylenic proton NMR coupling constants of 15 - 16 Hz, and also by a single crystal x-ray structure of the tetramethoxy compound 6. Continuous 3-day exposure of murine B16 melanoma cells to the trans-combretastatin analogs 5 - 13 showed that two of the analogs (2 and 4) had good cytotoxicity. According to a MTT assay, the IC50 values for compounds 2 and 4 were 4.5 Î¼M and 13.5 Î¼M, respectively. Compounds that exhibited cytotoxic properties contain a 4,4-dimethoxy-transstilbene skeleton.
Letters in Drug Design & Discovery