Design, synthesis and biological activities of tetrandrine and fangchinoline derivatives as antitumer agents

Dechao Li; Haizheng Liu; Yufa Liu; Qikun Zhang; Chao Liu; Shuhua Zhao; Bo Jiao

doi:10.1016/j.bmcl.2016.12.029

Design, synthesis and biological activities of tetrandrine and fangchinoline derivatives as antitumer agents

Bioorg Med Chem Lett. 2017 Feb 1;27(3):533-536. doi: 10.1016/j.bmcl.2016.12.029. Epub 2016 Dec 23.

Authors

Dechao Li¹, Haizheng Liu¹, Yufa Liu², Qikun Zhang¹, Chao Liu³, Shuhua Zhao³, Bo Jiao⁴

Affiliations

¹ College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, 88 East Wenhua Road, Jinan 250014, PR China.
² College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, 88 East Wenhua Road, Jinan 250014, PR China. Electronic address: liuyufa@sdnu.edu.cn.
³ Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, PR China.
⁴ School of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China.

PMID: 28057423
DOI: 10.1016/j.bmcl.2016.12.029

Abstract

The isolation and modification of natural products is always a very important resources to anti-tumor drugs. Therefore, a novel series of tetrandrine and fangchinoline derivatives were designed and synthesized, and their antiproliferative activities against HepG2, MCF-7 cells were evaluated and described. From the activity result obtained, high to very high activity in vitro has been found, one of the tested compounds (compound 5d) exhibited the most significant cytotoxic effects. Compound 5d increased 29.2, 7.37 times anti-proliferative activity for HepG2 cells and MCF-7 cells compared to sunitinib (IC₅₀=16.06μM and 25.41μM). Finally flow cytometry determined that compound 5d could indeed inhibit the proliferation of HepG2 cells via inducing apoptosis.

Keywords: Anti-tumor activity; Apoptosis; Fangchinoline; Tetrandrine.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Benzylisoquinolines / chemical synthesis
Benzylisoquinolines / chemistry
Benzylisoquinolines / pharmacology*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Design*
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
MCF-7 Cells
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents
Benzylisoquinolines
tetrandrine
fangchinoline