Synthesis and anticancer activity of novel 9,13-disubstituted berberine derivatives

Zhi-Cheng Wang; Jing Wang; Huang Chen; Jie Tang; Ai-Wu Bian; Ting Liu; Li-Fang Yu; Zhengfang Yi; Fan Yang

doi:10.1016/j.bmcl.2019.126821

Synthesis and anticancer activity of novel 9,13-disubstituted berberine derivatives

Bioorg Med Chem Lett. 2020 Jan 15;30(2):126821. doi: 10.1016/j.bmcl.2019.126821. Epub 2019 Nov 16.

Authors

Zhi-Cheng Wang¹, Jing Wang¹, Huang Chen², Jie Tang¹, Ai-Wu Bian², Ting Liu¹, Li-Fang Yu¹, Zhengfang Yi³, Fan Yang⁴

Affiliations

¹ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development & Shanghai Key Laboratory of Green Chemistry and Chemical Processes, SCME, East China Normal University, Shanghai 200062, China.
² Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
³ Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: zfyi@bio.ecnu.edu.cn.
⁴ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development & Shanghai Key Laboratory of Green Chemistry and Chemical Processes, SCME, East China Normal University, Shanghai 200062, China. Electronic address: fyang@chem.ecnu.edu.cn.

PMID: 31812467
DOI: 10.1016/j.bmcl.2019.126821

Abstract

Novel berberine derivatives with disubstituents on positions C9 and C13 were synthesized and evaluated for antiproliferative activities against human prostate cancer cell lines (PC3 and DU145), breast cancer cell line (MDA-MB-231) and human colon cancer cell lines (HT29 and HCT116). All compounds showed significantly enhanced antiproliferative activities compared with berberine. Notably, compound 18e exhibited the strongest cytotoxicity against PC3 cells with an IC₅₀ value of 0.19 μM, and the highest selectivity index (SI^PC3 > 20). Further studies showed that 18e could arrest the cell cycle at G1 phase, and significantly inhibit tumor cell colony forming and migration even at low concentrations. Interestingly, 18e could significantly induce cytoplasmic vacuolation, suggesting a different mode of action from berberine.

Keywords: Anticancer activity; Berberine derivatives; Cell migration; Colony forming; Lipophilic group.

Publication types

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

MeSH terms

Berberine / chemical synthesis*
Berberine / pharmacology
Berberine / therapeutic use*
Humans
Molecular Structure
Neoplasms / drug therapy*
Structure-Activity Relationship

Substances

Berberine