The synthesis and antistaphylococcal activity of 9, 13-disubstituted berberine derivatives

Jing Wang; Teng Yang; Huang Chen; Yun-Nan Xu; Li-Fang Yu; Ting Liu; Jie Tang; Zhengfang Yi; Cai-Guang Yang; Wei Xue; Fan Yang

doi:10.1016/j.ejmech.2017.01.012

The synthesis and antistaphylococcal activity of 9, 13-disubstituted berberine derivatives

Eur J Med Chem. 2017 Feb 15:127:424-433. doi: 10.1016/j.ejmech.2017.01.012. Epub 2017 Jan 9.

Authors

Jing Wang¹, Teng Yang², Huang Chen³, Yun-Nan Xu¹, Li-Fang Yu¹, Ting Liu¹, Jie Tang⁴, Zhengfang Yi³, Cai-Guang Yang⁵, Wei Xue⁶, Fan Yang⁷

Affiliations

¹ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China.
² Center for Research and Development of Fine Chemicals of Guizhou University, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guiyang 550225, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
³ Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
⁴ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China; Shanghai Key Laboratory of Green Chemistry and Chemical Processes, SCME, East China Normal University, Shanghai 200062, China.
⁵ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁶ Center for Research and Development of Fine Chemicals of Guizhou University, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guiyang 550225, China. Electronic address: wxue@gzu.edu.cn.
⁷ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China. Electronic address: fyang@chem.ecnu.edu.cn.

PMID: 28092858
DOI: 10.1016/j.ejmech.2017.01.012

Abstract

A series of novel 9, 13-disubstituted berberine derivatives have been synthesized and evaluated for the antibacterial activities against Staphylococcus aureus, including Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271). Compound 20 shows the most potent activity against the growth of Newman strain, with a MIC value of 0.78 μg/mL, which is comparable with the positive control vancomycin. In addition, compound 20, 21, and 33 are highly antistaphylococcal active against five strains of multidrug-resistant S. aureus, with MIC values of 0.78-1.56 μg/mL. Of note, theses antibacterial active compounds have no obvious toxicity to the viability of human fibroblast (HAF) cells at the MIC concentration.

Keywords: Antistaphylococcal activity; Berberine derivatives; Cytotoxicity; Multidrug-resistant.

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Anti-Bacterial Agents / toxicity
Berberine / chemical synthesis*
Berberine / chemistry
Berberine / pharmacology*
Berberine / toxicity
Cell Line
Chemistry Techniques, Synthetic
Humans
Methicillin-Resistant Staphylococcus aureus / drug effects*
Microbial Sensitivity Tests

Substances

Anti-Bacterial Agents
Berberine