PSU Research Offers New Hope in the Global Fight Against Drug-Resistant Malaria

A new federal grantis helping Portland State University researchers take a major step forward in the global fight against malaria, one of the deadliest infectious diseases in the world.

The National Institutes of Health (NIH) has awarded a total of $3.31 million over five years to a research team led by Papireddy Kancharla in PSU's Department of Chemistry, supporting the next stage of development for a promising new class of antimalarial drug candidates. The funding, which follows years of pioneering work, will allow scientists to refine and advance compounds that could become powerful tools against drug-resistant strains of the malaria parasite.

"Our ultimate goal is to deliver a new class of safe, effective and affordable anti-malarial drugs that can help save lives around the world," said Kancharla. "This new funding allows us to move much closer to that vision."

Our ultimate goal is to deliver a new class of safe, effective and affordable anti-malarial drugs that can help save lives around the world.

A Global Health Crisis Demanding New Solutions

Malaria infects roughly 200 million people and kills nearly half a million annually, mostly young children and pregnant women. Although existing treatments have saved countless lives, the parasite Plasmodiumis constantly evolving resistance to current drugs, creating an urgent need for new therapies.

That's where Kancharla's team comes in. In collaboration with Kevin Reynolds at PSU, Jane Kelly at the Portland VA Research Foundation and PSU, and Alison Roth at the Walter Reed Army Institute of Research, they have spent more than a decade developing and optimizing a class of compounds called tambjamines into highly promising new oral drug candidates.

"For centuries, nature has guided the fight against malaria. From quinine, derived from the bark of the cinchona tree; to artemisinin, extracted from a Chinese medicinal herb. Building on this legacy, our research team has been exploring new drug candidates inspired by natural products. One such discovery is a yellow pigmented compound-tambjamine-originally found in marine invertebrates and bacteria," Kancharla said.

These novel compounds stand out because they work in ways existing drugs do not. Early results show they are active against drug-sensitive and multidrug-resistantmalaria parasites and target multiple stages of the parasite's life cycle-including stages responsible for transmission-offering the potential for both treatment and prevention.

Breakthroughs to Build On

The research team's previous NIH-funded work produced encouraging results. Lead tambjamine candidates demonstrated:

• Fast action: Rapid parasite-killing activity on par with current frontline drugs.
• Multistage potency: Strong effects against liver-stage and blood-stage parasites, as well as those responsible for transmission to mosquitoes.
• Efficacy in animal models: Complete clearance of infection in mice following a single oral dose of treatment.

The compounds are also simple and cost-effective to produce, and early safety tests suggest a low risk of side effects.

What's Next: Turning Promising Science into Real Medicine

The new NIH renewal grant will fund the next critical steps: optimizing the compounds' pharmaceutical properties, improving their stability and bioavailability, and investigating how exactly they work at the molecular level. These advances are essential for moving the most promising candidates closer to clinical trials.

One major focus will be improving the compounds' performance in the body - particularly their metabolic stability - without sacrificing their potent antimalarial activity. Researchers will also collaborate with Dr. David Fidock at Columbia University to better understand the mechanism of action behind this new drug class.

If successful, this work could lay the foundation for a new generation of treatments - potentially used alone or in combination with existing therapies - to combat drug-resistant malaria and block its transmission.

For Kancharla and his team, the ultimate aim is ambitious but clear: to create a safe, affordable, and broadly effective malaria treatment that can save lives across the globe.