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Antineoplastic Agents. 606. The Betulastatins.
Journal of Natural Products 2018 March 24
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.
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