SC Connecticut News

Researchers have identified a new chemical compound, MED6-189, which shows strong inhibition of parasites resistant to commonly used antimalarial drugs. The compound's high potency, excellent therapeutic profile, and unique mode of action make it a promising addition to the antimalarial drug pipeline.

The study, funded by the National Institutes of Health, was published in Science.

Despite advancements in malaria prevention and treatment, the disease remains a significant public health threat globally. In 2022, malaria caused an estimated 247 million clinical cases and 619,000 deaths, according to the World Health Organization’s World Malaria Report 2023.

One major challenge in controlling malaria is the resistance of the parasite to commonly used antimalarial drugs. "Malaria is here to stay, and with widespread resistance, we need to join efforts to develop better therapeutic strategies," said Choukri Ben Mamoun, PhD, professor at Yale School of Medicine (YSM) and corresponding author of the study.

Researchers from YSM, the University of California, Irvine, and the University of California, Riverside employed a multidisciplinary approach to understand how MED6-189 works. The compound is a structural analogue of a marine sponge secondary metabolite.

“This study represents a true systems biology approach to antimalarial drug discovery and is an excellent example of a collaborative team-science effort incorporating expertise across multiple institutions and disciplines,” said Amy Bei, PhD, associate professor at Yale School of Public Health and co-author of the study.

In Plasmodium falciparum—the pathogen responsible for severe human malaria—MED6-189 inhibited both the parasite’s asexual development in blood and its ability to undergo sexual differentiation. Because MED6-189 targets multiple processes within the parasite, resistance development is less likely. “To render the compound ineffective, the parasite would need to alter multiple genes and metabolic functions,” Ben Mamoun explained.

This ability could also reduce the need for additional drugs and lower potential toxicity. Both Bei and Ben Mamoun emphasize the urgent need for continued optimization of this class of compounds and identification of novel antimalarials.

“In the context of emerging partial resistance to artemisinin-based combination therapies globally... identifying and validating promising new antimalarial leads requires an all-hands-on-deck collaborative approach,” Bei stated.

“Malaria is here to stay... This compound could function on its own like a combination therapy... much like we do with HIV and other diseases,” Ben Mamoun added.

Other authors include Zeinab Chahine, Steven Abel, Thomas Hollin, Griffin Lee Barnes, Jonathan Chung among others.

Yale School of Medicine’s Department of Internal Medicine Section focuses on comprehensive patient care, research, and educational activities for various infectious diseases. More information can be found at Infectious Diseases.