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A 4-cyano-3-methylisoquinoline inhibitor of Plasmodium falciparum growth targets the sodium efflux pump PfATP4

Gilson, Paul R.; Kumarasingha, Rasika; Thompson, Jennifer; Zhang, Xinxin; Sietsma Penington, Jocelyn; Kalhor, Robabeh; Bullen, Hayley E.; Lehane, Adele; Dans, Madeline G.; de Koning-Ward, Tania F.; Holien, Jessica K; da Costa, Tatiana P Soares; Kirk, Kiaran


We developed a novel series of antimalarial compounds based on a 4-cyano-3-methylisoquinoline. Our lead compound MB14 achieved modest inhibition of the growth in vitro of the human malaria parasite, Plasmodium falciparum. To identify its biological target we selected for parasites resistant to MB14. Genome sequencing revealed that all resistant parasites bore a single point S374R mutation in the sodium (Na+) efflux transporter PfATP4. There are many compounds known to inhibit PfATP4 and some...[Show more]

CollectionsANU Research Publications
Date published: 2019
Type: Journal article
Source: Scientific Reports
DOI: 10.1038/s41598-019-46500-5
Access Rights: Open Access


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