title: Identification of novel bivalent mimetics of annonaceous acetogenins via a scaffold-hopping strategy.
abstract: A series of novel bivalent mimetics of annonaceous acetogenins have been designed, synthesized, and evaluated. Among these, compound 7 bearing a homopiperazine ring in the middle region exhibited more potent growth inhibitory activity and higher selectivity against cancer cells over normal cells by comparison with AA005. This work indicates that modification of the middle piperazine ring is a useful optimizing tool for the simplified acetogenin mimetics.
authors.affiliation: Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Yanghan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Translational Imaging, The Houston Methodist Research Institute, Houston, TX 77030, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guang-Biao
authors.initials: GB
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Coordination Chemistry, Nanjing National Laboratory of Microstructures, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing 210093, China. Electronic address: yaoz@nju.edu.cn.
authors.forename: Zhu-Jun
authors.initials: ZJ
authors.lastname: Yao
authors.affiliation: Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: jiang_sheng@gibh.ac.cn.
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
mesh_terms: D054378:Acetogenins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D054378:Acetogenins; D000972:Antineoplastic Agents, Phytogenic
keywords: Annonaceous acetogenins; Bivalent analogues; Cytotoxicity; Homopiperazine; Selectivity