Biological evaluation of new mimetics of annonaceous acetogenins: alteration of right scaffold by click linkage with aromatic functionalities

Yanghan Liu; Qicai Xiao; Yongqiang Liu; Zheng Li; Yatao Qiu; Guang-Biao Zhou; Zhu-Jun Yao; Sheng Jiang

doi:10.1016/j.ejmech.2014.03.062

Biological evaluation of new mimetics of annonaceous acetogenins: alteration of right scaffold by click linkage with aromatic functionalities

Eur J Med Chem. 2014 May 6:78:248-58. doi: 10.1016/j.ejmech.2014.03.062. Epub 2014 Mar 21.

Authors

Yanghan Liu¹, Qicai Xiao¹, Yongqiang Liu², Zheng Li³, Yatao Qiu¹, Guang-Biao Zhou⁴, Zhu-Jun Yao⁵, Sheng Jiang⁶

Affiliations

¹ Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
² 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.
³ Department of Translational Imaging, The Houston Methodist Research Institute, Houston, TX 77030, United States.
⁴ 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. Electronic address: gbzhou@ioz.ac.cn.
⁵ 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.
⁶ Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: jiang_sheng@gibh.ac.cn.

PMID: 24686011
DOI: 10.1016/j.ejmech.2014.03.062

Abstract

A small library of analogues of annonaceous acetogenins through click linkage with aromatic moieties is established using a convergent modular fragment-assembly approach. These analogues exhibited low micromolar inhibitory activities against the proliferation of several human cancer cell lines. Structure-activity relationship (SAR) of these analogues indicates that replacement of the methoxy groups of ubiquinone ring with methyl groups is proved to be a useful strategy for improving the anticancer activity of quinone-acetogenin hybrids.

Keywords: Annonaceous acetogenins; Aromatic functionalities; Click chemistry; Cytotoxicity; Quinone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetogenins / chemistry
Acetogenins / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Benzoquinones / chemistry
Benzoquinones / pharmacology
Cell Proliferation / drug effects
Cell Survival / drug effects
Click Chemistry
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HCT116 Cells
Humans
Hydrocarbons, Aromatic / chemistry
Hydrocarbons, Aromatic / pharmacology*
Molecular Mimicry
Molecular Structure
Small Molecule Libraries / chemical synthesis
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology*
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Acetogenins
Antineoplastic Agents
Benzoquinones
Hydrocarbons, Aromatic
Small Molecule Libraries
quinone