2. Academic Validation
  3. Natural product-inspired aryl isonitriles as a new class of antimalarial compounds against drug-resistant parasites

Natural product-inspired aryl isonitriles as a new class of antimalarial compounds against drug-resistant parasites

  • Bioorg Med Chem. 2020 Oct 1;28(19):115678. doi: 10.1016/j.bmc.2020.115678.
Kwaku Kyei-Baffour 1,  Dexter C Davis 1,  Zarko Boskovic 2,  Nobutaka Kato 3,  Mingji Dai 4
Affiliations

Affiliations

  • 1 Department of Chemistry and Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
  • 2 Department of Medicinal Chemistry, University of Kansas, Lawrence, 66045 KS, USA.
  • 3 Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA. Electronic address: [email protected].
  • 4 Department of Chemistry and Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address: [email protected].
PMID: 32912433 DOI: 10.1016/j.bmc.2020.115678
Abstract

Malaria is a prevalent and deadly disease. The fast emergence of drug-resistant malaria parasites makes the situation even worse. Thus, developing new chemical entities, preferably with novel mechanisms of action, is urgent and important. Inspired by the complex and scarce isonitrile-containing terpene Natural Products, we evaluated a collection of easily prepared synthetic mono- and bis-isonitrile compounds, most of which feature a simple, but rigid stilbene backbone. From this collection, potent antimalarial lead compounds with EC50 value ranging from 27 to 88 nM against the Dd2 strain using a blood stage proliferation assay were identified. Preliminary SAR information showed that the isonitrile group is essential for the observed activity against the Dd2 strain and the bis-isonitrile compounds in general perform better than the corresponding mono-isonitrile compounds.

Keywords

Antimalarial; Drug discovery; Drug resistance; Isonitrile; Natural product; Stilbene; Terpene Isonitrile.

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