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Synthesis and structure-activity relationship studies of cytotoxic ester and ether anhydrovinblastine derivatives
Han-Kun Zhang1, Yong Shao, Hong Ding
1Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
Abstract:
Two new series of 3-demethoxycarbonyl-3-ester and 3-demethoxycarbonyl-3-ether methyl anhydrovinblastine derivatives were designed, synthesized, and evaluated for their inhibitory activities against human non-small-cell lung cancer (A549) and cervical epithelial adenocarcinoma (HeLa) cell lines. Ester anhydrovinblastine derivatives exhibited potent cytotoxicity, whereas the ether analogues were much less active. The size of the introduced substituents was the foremost factor in determining the resultant cytotoxic activity. Compound 12b showed a similar cytotoxic potency to the positive control, anhydrovinblastine (1a).
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