Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

ACS Infect Dis. 2018 Apr 13;4(4):431-444. doi: 10.1021/acsinfecdis.7b00197. Epub 2018 Mar 3.


Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain.

Keywords: fragments; malaria; native mass spectrometry; natural products; target identification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / isolation & purification*
  • Antimalarials / pharmacology*
  • Biological Products / isolation & purification*
  • Biological Products / pharmacology*
  • Drug Evaluation, Preclinical / methods*
  • Mass Spectrometry / methods*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / growth & development
  • Protein Binding
  • Protozoan Proteins / metabolism


  • Antimalarials
  • Biological Products
  • Protozoan Proteins