Evidence map›Paper›PMID 41371053›Full record

ArticleInternational journal for parasitology. Drugs and drug resistance2025

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

Liana Theodoridis, Carlo Giannangelo, Farrah El-Saafin, Mr Ranga Prabhath, Christopher A Macraild, Pallavi Sharma, Delphine Merino, Darren J Creek, Teresa G Carvalho

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Article in International journal for parasitology. Drugs and drug resistance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Liana TheodoridisDepartment of Microbiology, Anatomy, Physiology, and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, Australia.
Carlo GiannangeloDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, Monash University, Parkville, Australia.
Farrah El-SaafinOlivia Newton-John Cancer Research Institute, Heidelberg, Australia; School of Cancer Medicine, La Trobe University, Bundoora, Australia.
Mr Ranga PrabhathSchool of Chemistry, Joseph Banks Laboratory, University of Lincoln, LN6 7TS, UK.
Christopher A MacraildDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, Monash University, Parkville, Australia.
Pallavi SharmaSchool of Chemistry, Joseph Banks Laboratory, University of Lincoln, LN6 7TS, UK; La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
Delphine MerinoOlivia Newton-John Cancer Research Institute, Heidelberg, Australia; School of Cancer Medicine, La Trobe University, Bundoora, Australia; Department of Medical Biology, The Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Melbourne, Australia; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville Australia.
Darren J CreekDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, Monash University, Parkville, Australia.
Teresa G CarvalhoDepartment of Microbiology, Anatomy, Physiology, and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, Australia. Electronic address: t.carvalho@latrobe.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AntimalarialsArtemisininsDrug Resistance, MultipleMalaria, FalciparumPlasmodium falciparumCell LineDrug ResistanceErythrocytesHumansMetabolomicsAntimalarialsartemisininArtemisininsAntimalarialDrug discoveryHeterospirocyclesMalariaP. falciparum

Identifiers

PMID41371053
PMCPMC12743512

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.