title: Synthesis and structure-activity relationship studies of cytotoxic ester and ether anhydrovinblastine derivatives.
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).
authors.affiliation: 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.
authors.forename: Han-Kun
authors.initials: HK
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Shao
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Hu
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D004987:Ethers; C056817:3',4'-anhydrovinblastine; D014747:Vinblastine