Natural product-inspired aryl isonitriles as a new class of antimalarial compounds against drug-resistant parasites.
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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
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Journal | Bioorg Med Chem
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Volume | 28
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Issue | 19
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Pages | 115678
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Date Published | 2020 10 01
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ISSN | 1464-3391
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DOI | 10.1016/j.bmc.2020.115678
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PubMed ID | 32912433
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PubMed Central ID | PMC7509796
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Grant list | R35 GM128570 / GM / NIGMS NIH HHS / United States
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