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Exploration of 3-methylisoquinoline-4-carbonitriles as protein kinase A inhibitors of Plasmodium falciparum.

Buskes MJ, Harvey KL, Prinz B, Crabb BS, Gilson PR, Wilson DJ, Abbott BM

  • Journal Bioorganic & medicinal chemistry

  • Published 28 Mar 2016

  • Volume 24

  • ISSUE 11

  • Pagination 2389-96

  • DOI 10.1016/j.bmc.2016.03.048


A series of isoquinolines have been evaluated in a homology model of Plasmodium falciparum Protein Kinase A (PfPKA) using molecular dynamics. Synthesis of these compounds was then undertaken to investigate their structure-activity relationships. One compound was found to inhibit parasite growth in an in vitro assay and provides a lead to further develop 3-methylisoquinoline-4-carbonitriles as antimalarial compounds. Development of a potent and selective PfPKA inhibitor would provide a useful tool to shed further insight into the mechanisms enabling malaria parasites to establish infection.