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Bioaffinity Mass Spectrometry Screening.

Ben Yang1, Yun Jiang Feng1, Hoan Vu1

  • 1Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia.

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PubMed
Summary
This summary is machine-generated.

Researchers screened natural products for malaria drug targets. One extract and 11 fragments showed binding activity, with a new compound, arborside E, identified as a weak binder to Plasmodium falciparum Rab11a.

Keywords:
FTMSPfRab11amalaria

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Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Parasitology

Background:

  • Malaria remains a significant global health challenge, necessitating the discovery of novel therapeutic agents.
  • Plasmodium falciparum Rab11a (PfRab11a) is a potential drug target for antimalarial therapies.
  • Natural products represent a rich source of diverse chemical scaffolds for drug discovery.

Purpose of the Study:

  • To screen natural product extracts and a fragment library for compounds that bind to Plasmodium falciparum Rab11a (PfRab11a).
  • To identify novel antimalarial lead compounds targeting PfRab11a.

Main Methods:

  • Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) was employed for screening.
  • A library of 192 natural product extracts and 659 natural product-based fragments were tested.
  • Binding activity was confirmed using ESI-FTMS titration and orthogonal enzyme assays.

Main Results:

  • One natural product extract and 11 fragments exhibited binding activity to PfRab11a.
  • A new natural product, arborside E, was identified as a weak binder from the active extract of Psydrax montigena.
  • The binding and inhibitory activities of arborside E were validated.

Conclusions:

  • ESI-FTICR-MS is effective for screening natural products against malaria drug targets.
  • Arborside E and other identified compounds show potential as starting points for developing new antimalarial drugs targeting PfRab11a.