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Updated: Jan 9, 2026

Ookluc: A Plasmodium berghei Line for Identifying Transmission-blocking Compounds
Published on: July 11, 2025
Novel heterospirocyclic antimalarials with activity against artemisinin- and multidrug-resistant P. falciparum
Liana Theodoridis1, Carlo Giannangelo2, Farrah El-Saafin3
1Department of Microbiology, Anatomy, Physiology, and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, Australia.
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.
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