Antineoplastic Agents. 606. The Betulastatins

The medicinal potential of the plant pentacyclic triterpene betulin has generated long-term interest focused on various SAR research avenues. The present approach was based on producing further analogues (chimeras) arising from a studied modification of betulin bonded to the Dov-Val-Dil-Dap unit of the powerful Anticancer drug dolastatin 10, which provided betulastatins 1 (7b), 2 (11b), 3 (16b), and 4 (18b). Betulastatin 1, 2, and 4 exhibited modest levels of Cancer cell growth inhibition against six Cancer cell lines. Betulastatin 3 proved to be the most potent Cancer cell growth inhibitor (GI₅₀ 0.01 μg/mL) and seems worthy of further development, as the presumed mixture of Anticancer mechanisms of action may prove to be useful.