Exploration of 3-methylisoquinoline-4-carbonitriles as protein kinase A inhibitors of Plasmodium falciparum. Issue 11 (1st June 2016)

• Record Type: Journal Article
• Authors: Buskes, Melissa J.; Harvey, Katherine L.; Prinz, Boris; Crabb, Brendan S.; Gilson, Paul R.; Wilson, David J.D.; Abbott, Belinda M.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 11(2016)
• Page Start: 2389
• Page End: 2396
• Publication Date: 2016-06-01
• Subjects: Isoquinolines -- Protein Kinase A -- Antimalarials -- Inhibitors; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.03.048
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A series of isoquinolines have been evaluated in a homology model of Plasmodium falciparum Protein Kinase A ( Pf PKA) 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 Pf PKA inhibitor would provide a useful tool to shed further insight into the mechanisms enabling malaria parasites to establish infection.