Promising new antimalarial compound discovered

Date:
October 27, 2021
Source:
McMaster University
Summary:
A discovery opens the door to the development of new drugs targeting
malaria, one of the deadliest infectious diseases on the planet. The
researcher teams performed a screen of soil bacteria extracts
for antimalarials and identified an extremely potent inhibitor of
malaria development.



FULL STORY ==========================================================================
A study out of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University has resulted in the discovery of a
promising new antimalarial compound.


========================================================================== Co-led by Gerry Wright, professor of biochemistry & biomedical sciences,
the discovery opens the door to the development of new drugs targeting
malaria, one of the deadliest infectious diseases on the planet.

Collaborating with professor Tim Gilberger of the University of Hamburg
in Germany, the researcher teams performed a screen of soil bacteria
extracts for antimalarials and identified an extremely potent inhibitor
of malaria development.

"We've shined a new light here," said Wright, the inaugural lead
of Canada's Global Nexus for Pandemics and Biological Threats at
McMaster. "We're looking at a part of chemistry that nobody has ever
looked at before." This breakthrough, published today in Cell Chemical Biology, comes at a pivotal time in global malaria management, Wright
said.

Drug resistance in malaria is becoming "a huge problem," he said, and
climate change is pushing malaria-carrying mosquitoes to new places,
broadening the disease's spread. The World Health Organization estimates
that malaria was responsible for more than 400,000 deaths and 229 million infections in 2019 alone.



========================================================================== Wright said that the family of compounds under study -- 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. Wright calls these compounds 'anti-life,' since
they kill just about everything in their path.

However, PDE-I2,the new compound molecule discovered by the
McMaster-Hamburg team, appears to come with all of the potent
malaria-killing properties of previously known duocarmycins -- just
without the adverse effects.

Wright said the discovery was a decade in the making, beginning when he
and Gilberger worked together at McMaster between 2010 and 2014.

Since then, the Wright laboratory has been sending thousand of
sub-fractions from Hamilton to Hamburg, where Gilberger and his team
would assay them against malaria parasites at the Bernhard Nocht Institute
for Tropical Medicine.

It was years of trial-and-error before the researchers finally
fractionated the right molecule -- a process Wright likens to finding
a needle in a haystack.

"This novel compound represents a useful scaffold for anti-malaria
therapy," said Gilberger, who added that he is excited to explore its 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.

========================================================================== Story Source: Materials provided by McMaster_University. Original written
by Blake Dillon.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Arne Alder, Nicole S. Struck, Min Xu, Jarrod W. Johnson, Wenliang
Wang,
Daniel Pallant, Michael A. Cook, Janis Rambow, Sarah Lemcke, Tim W.

Gilberger, Gerard D. Wright. A non-reactive natural product
precursor of the duocarmycin family has potent and selective
antimalarial activity.

Cell Chemical Biology, 2021; DOI: 10.1016/j.chembiol.2021.10.005 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211027135002.htm

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