Synthesis and structure-activity relationship studies of cytotoxic ester and ether anhydrovinblastine derivatives.
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).
Zhang
Han-Kun
HK
Shanghai 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.
Shao
Yong
Y
Ding
Hong
H
Hu
Li-Hong
LH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D004354:Drug Screening Assays, Antitumor; D004952:Esters; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D004952:Esters; D004987:Ethers; C056817:3',4'-anhydrovinblastine; D014747:Vinblastine