Title: A Stereospecific Route for the Preparation of Trans-Combretastatin Analogs: Synthesis and Cytotoxicity
Volume: 1
Issue: 3
Author(s): Hari Pati, Zarmeen Taherbhai, Lori Forrest, Martha Wicks, Suzanna Bailey, Andrew Staples, Michelle Stewart, William Pennington, Jeffrey Harris and Moses Lee
Affiliation:
Keywords:
combretastatin, tubulin, anticancer, chugaev reaction, cytotoxicity
Abstract: 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 μM and 13.5 μM, respectively. Compounds that exhibited cytotoxic properties contain a 4,4-dimethoxy-transstilbene skeleton.
