Molecular Diversity

, Volume 18, Issue 3, pp 621–635

System-level multi-target drug discovery from natural products with applications to cardiovascular diseases

Authors

  • Chunli Zheng
    • Center of Bioinformatics, College of Life ScienceNorthwest A&F University
  • Jinan Wang
    • Center of Bioinformatics, College of Life ScienceNorthwest A&F University
  • Jianling Liu
    • College of Life ScienceNorthwest University
  • Mengjie Pei
    • College of Life ScienceNorthwest University
  • Chao Huang
    • Center of Bioinformatics, College of Life ScienceNorthwest A&F University
    • Center of Bioinformatics, College of Life ScienceNorthwest A&F University
Full-Length Paper

DOI: 10.1007/s11030-014-9521-y

Cite this article as:
Zheng, C., Wang, J., Liu, J. et al. Mol Divers (2014) 18: 621. doi:10.1007/s11030-014-9521-y

Abstract

The term systems pharmacology describes a field of study that uses computational and experimental approaches to broaden the view of drug actions rooted in molecular interactions and advance the process of drug discovery. The aim of this work is to stick out the role that the systems pharmacology plays across the multi-target drug discovery from natural products for cardiovascular diseases (CVDs). Firstly, based on network pharmacology methods, we reconstructed the drug–target and target–target networks to determine the putative protein target set of multi-target drugs for CVDs treatment. Secondly, we reintegrated a compound dataset of natural products and then obtained a multi-target compounds subset by virtual-screening process. Thirdly, a drug-likeness evaluation was applied to find the ADME-favorable compounds in this subset. Finally, we conducted in vitro experiments to evaluate the reliability of the selected chemicals and targets. We found that four of the five randomly selected natural molecules can effectively act on the target set for CVDs, indicating the reasonability of our systems-based method. This strategy may serve as a new model for multi-target drug discovery of complex diseases.

Keywords

Systems pharmacology Multi-target drugs Cardiovascular diseases Natural products Polypharmacology

Supplementary material

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Copyright information

© Springer International Publishing Switzerland 2014