Retargeting azithromycin analogues to have dual-modality antimalarial activity
Amy L Burns, Brad E Sleebs, Ghizal Siddiqui, Amanda E De Paoli, Dovile Anderson, Benjamin Liffner, Richard Harvey, James G Beeson, Darren J Creek, Christopher D Goodman, Geoffrey I McFadden, Danny W Wilson
BMC Biology | BioMed Central | Published : 2020
Background Resistance to front-line antimalarials (artemisinin combination therapies) is spreading, and development of new drug treatment strategies to rapidly kill Plasmodium spp. malaria parasites is urgently needed. Azithromycin is a clinically used macrolide antibiotic proposed as a partner drug for combination therapy in malaria, which has also been tested as monotherapy. However, its slow-killing ‘delayed-death’ activity against the parasite’s apicoplast organelle and suboptimal activity as monotherapy limit its application as a potential malaria treatment. Here, we explore a panel of azithromycin analogues and demonstrate that chemical modifications can be used to greatly improve the ..View full abstract
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Awarded by National Health and Medical Research Council of Australia
This work was made possible through the National Health and Medical Research Council of Australia (Project Grant 1143974 to D.W.W., G.I.M, B.E.S. and C.D.G; Development Grant 1113712 to B.E.S.; Senior Research Fellowship 1077636 to JGB; Career Development (II) Fellowship 1148700 to DJC) and the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. D.W.W. is a University of Adelaide Beacon Fellow and Hospital Research Foundation Fellow. B.E.S. is a Corin Centenary Fellow.