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.
Shao
Yong
Y
Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
Ding
Hong
H
Tang
Weidong
W
Lou
Liguang
L
Hu
Lihong
L
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D013047:Specific Pathogen-Free Organisms; D013329:Structure-Activity Relationship; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014747:Vinblastine