Synthesis and structure–activity relationships study of novel anti-tumor carbamate anhydrovinblastine analogues

A series of 3-demethoxycarbonyl-3-carbamate methyl anhydrovinblastine derivatives (compounds 8b–32b) were designed, synthesized, and evaluated for their inhibition activities against human non-small cell lung cancer cell line (A549) and a human cervix epithelial adenocarcinoma cell line (HeLa). The structure–activity relationships of this new series are described in this paper. Cytotoxicity data revealed that the size of substituents and substitution position had important influence on cytotoxic activity. On two cell lines, compounds (8b and 30b) had more potent cytotoxic activity than the lead compound (1e, AVLB). The preliminary antitumor studies of 8b in vivo showed that it might be promising for the development of new antitumor agents.

A new series of 3-demethoxycarbonyl-3-carbamate methyl anhydrovinblastine derivatives were synthesized and evaluated the cytotoxic activity in vitro against A549 and HeLa cell lines (IC50: 38–609 nM and 6–387 nM, respectively). The SARs of this new series are reported.Figure optionsDownload as PowerPoint slide