RETARGETING THE ANTIBIOTIC AZITHROMYCIN AS AN ANTIMALARIAL WITH DUAL MODALITY
Grant number: 1143974 | Funding period: 2018 - 2021
Malaria parasites resistant to first-line treatments continue to spread in South East Asia. New drugs need to be developed urgently to ensure alternative treatment strategies are available. We will retarget the safe and widely used antibiotic azithromycin as an antimalarial with dual modalities against parasite invasion and growth inside the host red blood cell. This strategy has significant potential to increase drug efficacy while reducing the chances for the development of resistance.
Related publications (8)
Cell biological analysis reveals an essential role for Pfcerli2 in erythrocyte invasion by malaria parasites
Benjamin Liffner, Juan Miguel Balbin, Gerald J Shami, Ghizal Siddiqui, Jan Strauss, Sonja Frolich, Gary K Heinemann, Ella May Edwards, Arne Alder, Jan Stephan Wichers, Darren J Creek, Leann Tilley, Matthew WA Dixon, Tim-Wolf Gilberger, Danny W Wilson
Merozoite invasion of host red blood cells (RBCs) is essential for survival of the human malaria parasite Plasmodium falciparum. P..
Property activity refinement of 2-anilino 4-amino substituted quinazolines as antimalarials with fast acting asexual parasite activity
Trent D Ashton, Anna Ngo, Paola Favuzza, Hayley E Bullen, Maria R Gancheva, Ornella Romeo, Molly Parkyn Schneider, Nghi Nguyen, Ryan WJ Steel, Sandra Duffy, Kym N Lowes, Helene Jousset Sabroux, Vicky M Avery, Justin A Boddey, Danny W Wilson, Alan F Cowman, Paul R Gilson, Brad E Sleebs
Malaria is a devastating disease caused by Plasmodium parasites. Emerging resistance against current antimalarial therapeutics has..
Optimisation of 2-(N-phenyl carboxamide) triazolopyrimidine antimalarials with moderate to slow acting erythrocytic stage activity
Brodie L Bailey, William Nguyen, Anna Ngo, Christopher D Goodman, Maria R Gancheva, Paola Favuzza, Laura M Sanz, Francisco-Javier Gamo, Kym N Lowes, Geoffrey I McFadden, Danny W Wilson, Benoit Laleu, Stephen Brand, Paul F Jackson, Alan F Cowman, Brad E Sleebs
Malaria is a devastating parasitic disease caused by parasites from the genus Plasmodium. Therapeutic resistance has been reported..
Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion
William Nguyen, Madeline G Dans, Anna Ngo, Maria R Gancheva, Ornella Romeo, Sandra Duffy, Tania F de Koning-Ward, Kym N Lowes, Helene Jousset Sabroux, Vicky M Avery, Danny W Wilson, Paul R Gilson, Brad E Sleebs
The emerging resistance to combination therapies comprised of artemisinin derivatives has driven a need to identify new antimalari..
Optimization of Benzothiazole and Thiazole Hydrazones as Inhibitors of Schistosome BCL-2
William Nguyen, Erinna F Lee, Marco Evangelista, Mihwa Lee, Tiffany J Harris, Peter M Colman, Nicholas A Smith, Luke B Williams, Kate E Jarman, Kym N Lowes, Cecile Haeberli, Jennifer Keiser, Brian J Smith, W Douglas Fairlie, Brad E Sleebs
Limited therapeutic options are available for the treatment of human schistosomiasis caused by the parasitic Schistosoma flatworm...
Development and application of a high-throughput screening assay for identification of small molecule inhibitors of the P. falciparum reticulocyte binding-like homologue 5 protein
Brad E Sleebs, Kate E Jarman, Sonja Frolich, Wilson Wong, Julie Healer, Weiwen Dai, Isabelle S Lucet, Danny W Wilson, Alan F Cowman
The P. falciparum parasite, responsible for the disease in humans known as malaria, must invade erythrocytes to provide an environ..
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
Background Resistance to front-line antimalarials (artemisinin combination therapies) is spreading, and development of new drug tr..