title: Novel Azetidine-Containing TZT-1027 Analogues as Antitumor Agents.
abstract: A conformational restriction strategy was used to design and synthesize nine TZT-1027 analogues. 3-Aryl-azetidine moiety was used to replace phenylethyl group of TZT-1027 at the C-terminus. These analogues exhibited moderate to excellent antiproliferative activities, and the most potent compound 1a showed IC50 values of 2.2 nM against A549 and 2.1 nM against HCT116 cell lines, respectively. However, 1a could not achieve effective inhibition at all the dose levels in the A549 xenograft model (up to 5 mg/kg, injection, once a day), which is only 16%-35% inhibition at the end of the experiment.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China. yanq12@fudan.edu.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China. wyjbljy@163.com.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China. zhangw416@fudan.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China. liyx417@fudan.edu.cn.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Li
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001384:Azetidines / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001384:Azetidines; D009842:Oligopeptides; C105791:soblidotin
keywords: TZT-1027; antiproliferative activity; azetidine; conformation restriction