Anti-cancer molecules show promise in the fight against malaria

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Molecules known for their anticancer activity have proven effective against Plasmodium falciparum, the parasite that causes malaria. Researchers at the University of São Paulo's School of Pharmaceutical Sciences (FCF-USP) in Brazil also investigated how differences in the molecules' structure affect their impact on the parasite. The research paves the way for more effective drugs.

According to estimates by the World Health Organization (WHO), malaria caused approximately 600,000 deaths in 2024. Célia Regina da Silva Garcia, a professor in the Department of Clinical and Toxicological Analysis at FCF-USP, says an estimated 90% of those deaths were caused by P. falciparum. Although malaria treatments exist, the parasite has become more resistant to drugs such as chloroquine and artemisinin, making new treatments necessary. Repurposing drugs already used for other purposes offers a faster, cheaper alternative in the search for new treatments.

Attacking two stages of infection

Fourteen compounds derived from an antineoplastic drug (used to treat cancer) were tested on P. falciparum parasites cultured in the laboratory. The molecules eliminated the parasites at two stages of development: the asexual and gametocyte stages.

By eliminating the parasite in the asexual stage, when it reproduces in blood cells and causes the fever typical of malaria, the compounds show potential as treatments. The molecules also act during the gametocyte stage, when Plasmodium infects mosquitoes. In addition to treating patients, the drugs could block transmission of the disease.

Safety remains uncertain beyond cell tests

Despite the promising results published in July in the journal ACS Omega, concerns remain about possible side effects. Only in vitro tests have been conducted so far, so the extent of the problem has not been assessed. Some compounds showed reduced efficacy in tests with human cells while maintaining their effect on the parasites. This indicates a lower risk of serious adverse effects, but only in vivo tests can confirm that.

"Molecules in that class can cause fatigue, nausea, vomiting and hematological changes, such as a decrease in platelets. It's natural for that concern to exist," Garcia says. In vivo tests are also important for determining whether the drug candidates remain stable in a patient's body, since drugs in this class tend to degrade rapidly under those conditions.

Refining molecules for different parasites

To overcome these limitations, Garcia's team analyzed how variations in the structure of the derivatives affect their function and identified their target within the parasite's cells. This could help researchers develop drugs better suited for treatment. "When we engage in rational drug design of new molecules, we can refine their chemical structure in a targeted manner. Our experiments have strengthened the hypothesis that histone deacetylase enzymes are an important therapeutic target for malaria. As a result, we've been able to design new molecules that are increasingly potent and selective against the parasite," Garcia explains.

Garcia's team also plans to test the molecules on other malaria-causing parasite species, such as Plasmodium vivax, which is prevalent in Brazil and can cause relapses even after treatment. "P. vivax can also develop latent forms known as hypnozoites that lodge in the liver. Furthermore, it's more widespread in equatorial countries. Therefore, it's important to evaluate the efficacy of antimalarial drugs against different species to ensure they're effective in various regions of the world," Garcia says.

Publication details

Bárbara K.M. Dias et al, Repurposing 6-Anilinopurine Derivatives That Exhibit PfHDAC1 Inhibition and Antimalarial Activity against Asexual and Sexual Stages of Plasmodium falciparum, ACS Omega (2026). DOI: 10.1021/acsomega.5c12744

Journal information: ACS Omega

Key medical concepts

Plasmodium falciparumMalariaHistone Deacetylases

Clinical categories

Infectious diseasesClinical pharmacology Provided by FAPESP Who's behind this story?

Gaby Clark

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