Promising new antimalarial compound discovered

Kooperationserfolg Hamburg und Hamilton, Kanada

Wissenschaftlerinnen und Wissenschaftler um Prof. Tim Gilberger am Zentrum für Strukturelle Systembiologie (Centre for Structural Systems Biology, CSSB) in Hamburg sowie Prof. Gerry Wright am Michael G. DeGroote Institute for Infectious Disease Research an der McMaster University in Hamilton, Kanada, haben einen vielversprechenden neuen Wirkstoff gegen den Malaria-Erreger entdeckt. Die Forschungsergebnisse sind nun in der Fachzeitschrift Cell Chemical Biology veröffentlicht worden. Damit werden neue Ansätze für die Entwicklung von Medikamenten gegen Malaria – eine der tödlichsten Infektionskrankheiten in Subsahara Afrika, aufgezeigt.

The image shows the chemical formula of the potential new malaria drug.
©BNITM | Tim Gilberger

Double challenge: Drug-resistance and climate change

Co-led by Tim Gilberger (Bernhard-Nocht-Institute for Tropical Medicine / Universität Hamburg) and Gerry Wright (Michael G. DeGroote Institute for Infectious Disease Research, McMaster University in Hamilton, Canada) the researcher teams performed a screen of soil bacteria extracts for antimalarials and identified an extremely potent inhibitor of malaria development.

This breakthrough comes at a pivotal time in global malaria management as drug resistance in malaria is becoming increasingly problematic and climate change is pushing malaria-carrying mosquitoes to new places, broadening the disease’s spread. In fact, World Health Organization (WHO) estimates that malaria was responsible for more than 400,000 deaths and 229 million infections in 2019 alone.

Trial and Error Research

The family of compounds investigated by the researchers — duocarmycins — have been known to kill malaria and cancer cells for some time; however, they are extremely toxic to humans. As such, using them as treatment comes with considerable collateral damage, which has resulted in many failed clinical trials. These compounds considered to be ‘anti-life,’ as they kill just about everything in their path.

However, PDE-I2, the new compound molecule discovered by the Hamburg- McMaster team, appears to come with all of the potent malaria-killing properties of previously known duocarmycins — just without the adverse effects. “We’ve shone a new light here,” said Wright “We’re looking at a part of chemistry that nobody has ever looked at before.”

The project began when Gilberger and Wright worked together at McMaster between 2010 and 2014. Since then, the Wright laboratory has been sending thousands of sub-fractions derived from specific soil bacteria from Hamilton to Hamburg, where Gilberger and his team would test and validate their anti-malarial activity.

Figure on the effectiveness of PDE-I2.
PDE-I2 is potent, non-toxic, and active in a stage-specific manner against P. falciparum   ©BNITM | Tim Gilberger
Visualisation of phenotype screening of anti-malarial extracts
Phenotype screening of anti-malarial extracts   ©BNITM | Tim Gilberger

After years of experimentation, the researchers finally isolated the right molecule. “This novel compound represents a useful scaffold for anti-malaria therapy,” said Gilberger, who added that he is excited to explore the compounds efficiency in systemic infections and to pinpoint its mode of action.


The main funding for the research study came from the Canadian Institutes for Health Research. Additional funding was received from the Jürgen Manchot Stiftung, the Joachim Herz Stiftung and PIER/DESY.

Original publication



A screen of blood stage P. falciparum against a library of microbial NP extracts
A screen of blood stage P. falciparum against a library of microbial NP extracts   ©BNITM | Tim Gilberger

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