Journal article
Antimalarial activity of novel 4-cyano-3-methylisoquinoline inhibitors against: Plasmodium falciparum: Design, synthesis and biological evaluation
MJ Buskes, KL Harvey, BJ Richards, R Kalhor, RM Christoff, CK Gardhi, DR Littler, ED Cope, B Prinz, GE Weiss, NJ O'Brien, BS Crabb, LW Deady, PR Gilson, BM Abbott
Organic and Biomolecular Chemistry | ROYAL SOC CHEMISTRY | Published : 2016
DOI: 10.1039/c5ob02517f
Abstract
Central to malaria pathogenesis is the invasion of human red blood cells by Plasmodium falciparum parasites. Following each cycle of intracellular development and replication, parasites activate a cellular program to egress from their current host cell and invade a new one. The orchestration of this process critically relies upon numerous organised phospho-signaling cascades, which are mediated by a number of central kinases. Parasite kinases are emerging as novel antimalarial targets as they have diverged sufficiently from their mammalian counterparts to allow selectable therapeutic action. Parasite protein kinase A (PfPKA) is highly expressed late in the cell cycle of the parasite blood st..
View full abstractGrants
Funding Acknowledgements
M.B. acknowledges the support of the CRC for Biomarker Translation, funded by the Australian Government, in the provision of her postgraduate scholarship. K.H. is the recipient of an Australian Postgraduate Award from the University of Melbourne, Australia. The authors also wish to acknowledge the undergraduate chemistry students who contributed to this project, Banin Rasouli, Dylan Smith, Nikolaj Villadsen, Kristofer Cupic and Bethany Davey (Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University). We also acknowledge the contribution made by Dr Jason Dang (Monash Institute of Pharmaceutical Sciences, Monash University) for HRMS analysis and the MRC PPU International Centre for Kinase Profiling (University of Dundee, United Kingdom) for the human kinase screening. This work was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia. The authors gratefully acknowledge the contribution of the Victorian Operational Infrastructure Support Program, Australia received by the Burnet Institute and Monash Micro Imaging.