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

Bioorg Med Chem
Authors
Keywords
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 EC 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.

Year of Publication
2020
Journal
Bioorg Med Chem
Volume
28
Issue
19
Pages
115678
Date Published
2020 10 01
ISSN
1464-3391
DOI
10.1016/j.bmc.2020.115678
PubMed ID
32912433
PubMed Central ID
PMC7509796
Links
Grant list
R35 GM128570 / GM / NIGMS NIH HHS / United States