Targeting malaria parasites with novel derivatives of azithromycin

AL Burns; BE Sleebs; M Gancheva; KT McLean; G Siddiqui; H Venter; JG Beeson; R O’Handley; DJ Creek; S Ma; S Frölich; CD Goodman; GI McFadden; DW Wilson

Journal article

Targeting malaria parasites with novel derivatives of azithromycin

AL Burns, BE Sleebs, M Gancheva, KT McLean, G Siddiqui, H Venter, JG Beeson, R O’Handley, DJ Creek, S Ma, S Frölich, CD Goodman, GI McFadden, DW Wilson

Frontiers in Cellular and Infection Microbiology | Published : 2022

DOI: 10.3389/fcimb.2022.1063407

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Abstract

Introduction: The spread of artemisinin resistant Plasmodium falciparum parasites is of global concern and highlights the need to identify new antimalarials for future treatments. Azithromycin, a macrolide antibiotic used clinically against malaria, kills parasites via two mechanisms: ‘delayed death’ by inhibiting the bacterium-like ribosomes of the apicoplast, and ‘quick-killing’ that kills rapidly across the entire blood stage development. Methods: Here, 22 azithromycin analogues were explored for delayed death and quick-killing activities against P. falciparum (the most virulent human malaria) and P. knowlesi (a monkey parasite that frequently infects humans). Results: Seventeen analogues..

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University of Melbourne Researchers

Brad Sleebs Author

James Beeson Author

Christopher Dean Goodman Author

Geoffrey McFadden Author

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Grants

Awarded by National Institutes of Health

Funding Acknowledgements

This work was made possible through the National Health and Medical Research Council of Australia (Project Grant 1143974 to DW, GM, BS, and CG; Development Grant 1113712 to BS; Career Development (II) Fellowship 1148700 to DC) and the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. DW is a Hospital Research Foundation Fellow, BS is a Corin Centenary Fellow, JB is an NHMRC Investigator GrantFellow 1173046, AB was supported by an ARC-RTP scholarship. This work is supported by NIH grant U2C-DK119886.