Journal article
Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion
W Nguyen, MG Dans, A Ngo, MR Gancheva, O Romeo, S Duffy, TF de Koning-Ward, KN Lowes, HJ Sabroux, VM Avery, DW Wilson, PR Gilson, BE Sleebs
European Journal of Medicinal Chemistry | Published : 2021
Abstract
The emerging resistance to combination therapies comprised of artemisinin derivatives has driven a need to identify new antimalarials with novel mechanisms of action. Central to the survival and proliferation of the malaria parasite is the invasion of red blood cells by Plasmodium merozoites, providing an attractive target for novel therapeutics. A screen of the Medicines for Malaria Venture Pathogen Box employing transgenic P. falciparum parasites expressing the nanoluciferase bioluminescent reporter identified the phenylsulfonyl piperazine class as a specific inhibitor of erythrocyte invasion. Here, we describe the optimization and further characterization of the phenylsulfonyl piperazine ..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This research was funded by the National Health and Medical Research Council (NHMRC) of Australia (Development Grant 1135421 to B.E.S., P.R.G. and V.M.A.; Project Grant 1143974 to D.W.W. and B.E.S.), the Australian Cancer Research Foundation, Australian Government Research Training Program Scholarship (to M.G.D.), the Victorian State Government OIS and Australian Government NHMRC IRIISS. B.E.S. is a Corin Centenary Fellow and D.W.W. is a Hospital Research Foundation Fellow. We thank and acknowledge the Australian Red Cross Blood Bank for the provision of fresh red blood cells, without which this research could not have been performed. We thank Dr Andrew Powell for useful discussions; Prof Alan Cowman and Dr Kitsanapong Reaksudsan for the provision of 3D7 parasites for the LDH asexual assay and Emily Kennedy for technical assistance with the gametocyte assays.