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Novel heterospirocyclic antimalarials with activity against artemisinin- and multidrug-resistant P. falciparum malaria

Year: 2025
Type: article
Abstract: Malaria is an infectious disease that imposes a significant global health burden. Increasing drug resistance creates an urgent demand for novel treatment options. We have previously synthesised a new class of heterospirocyclic compounds with novel chemical linkages, which have shown preliminary antimalarial activity. Compounds 25 and 26 display antimalarial activity within 24 h against a panel of drug-resistant strains of Plasmodium falciparum, the most virulent of human malaria parasites. Untargeted metabolomics analysis of P. falciparum-infected red blood cells revealed that the mechanism of action of compound 25 could involve disruption of the pyrimidine biosynthesis pathway and haemoglobin catabolism. Further, compounds 25 and 26 do not induce major toxicity in kidney- and hepatic-derived human cell lines, highlighting their specificity. These heterospirocyclic compounds represent a promising opportunity for antimalarial drug development and could prove relevant against drug-resistant malaria.
DOI: 10.1016/j.ijpddr.2025.100627
Authors: Liana Theodoridis, Carlo Giannangelo, Farrah El-Saafin, MR Ranga Prabhath, Christopher A. Macraild, Pallavi Sharma, Delphine Merino, Darren J. Creek, Teresa G. Carvalho
Institutions: La Trobe University, Monash University, Olivia Newton-John Cancer Wellness & Research Centre, Olivia Newton-John Cancer Research Institute, University of Lincoln, The University of Melbourne, Walter and Eliza Hall Institute of Medical Research
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,700
OpenAlex ID: W4417067318
FWCI:
Cites: 29
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