Dolastatin 11 is a highly cytotoxic nonadepsipeptide found in very small amounts in a marine animal. As its cytotoxicity is due to interference with the formation of microfilaments and there are as yet no clinically used microfilament inhibitors, it offers hope of a new mode of attack upon cancer. A recent highly convergent synthesis of dolastatin 11 established its stereochemistry and made possible the synthesis of analogues. About 30 analogues of dolastatin 11 have been selected for this study to define the pharmacophore and in the hope of finding simpler active compounds. They will be synthesized at the University of Arizona, where the synthesis was developed, and tested for cytotoxicity at Arizona State University (Pettit's group) and the National Cancer Institute (Hamel and coworkers). Hamel is also attempting biological studies aimed at identifying the receptor and clarifying the mode of action.
| Ali, Md Ahad; Bates, Robert B; Crane, Zackary D et al. (2005) Dolastatin 11 conformations, analogues and pharmacophore. Bioorg Med Chem 13:4138-52 |
| Bai, Ruoli; Bates, Robert B; Hamel, Ernest et al. (2002) Lyngbyastatin 1 and Ibu-epilyngbyastatin 1: synthesis, stereochemistry, and NMR line broadening. J Nat Prod 65:1824-9 |
