News Feature | December 8, 2014

Researchers Identify New Class Of Antimalarial Agents

By C. Rajan, contributing writer

Researchers have found a new class of molecules that is highly potent against the human malaria parasites and causes the parasites’ guts to swell up and explode, CBS News reported. The new class of antimalarial agents works by inhibiting the malaria parasites' ability to maintain sufficient levels of sodium within their cells, leading to excessive water intake.

The international team of researchers, led by Dr. Akhil Vaidya at Drexel University, discovered a new class of compounds, known as pyrazoleamides, which were effective against the two major parasite species causing malaria, Plasmodium falciparum and Plasmodium vivax.

These new compounds affect a molecular pump that helps the malaria parasite to control its own sodium levels. As a result, the parasite fills with water to balance the sodium levels, swells up rapidly, and then bursts and dies.

Malaria is a deadly mosquito-borne disease that is caused by Plasmodium parasites, with symptoms including fever, vomiting, seizures, and sweating. According to WHO estimates, there are nearly 300 million cases of malaria every year with nearly 600,000 deaths worldwide. While malaria is more prevalent in Asia and Africa, it has spread to other parts of the world, including the U.S., due to climate change and global travel.

Malaria is becoming a serious global concern due to increasing drug resistance to leading antimalarial agents like artemisinin and chloroquine.

“Many of the existing antimalarial drugs stop working because of resistance development, so it is essential to feed the pipeline with new antimalarial drugs through discovery and development,” says Dr. Vaidya, whose malaria research has been funded by a $2 million grant from the NIH.

The researchers say that the new pyrazoleamide compounds work rapidly through a novel mechanism in malaria parasites, and thus would work against the drug resistant malaria parasites also.

Another interesting property of the new agents was their activity against the reproductive stages of the parasites. By inhibiting the reproduction, the new agents will likely also prevent onward transmission of the parasite by mosquitoes.

There is another recently developed drug that works in a similar manner to the pyrazoleamides, says Dr. Vaidya. Novartis’ new promising malaria drug candidate, KAE609 or cipragamin, has a different chemical structure but the same mechanism of action. Novartis recently reported that KAE609 was able to successfully clear the mosquito parasite from infected patients within 12 hours.

Dr. Vaidya and his team screened millions of compounds and identified one of the new molecules for further development as a candidate antimalarial drug. However, Dr. Vaidya cautions that it could be a long time before the new compound actually leads to a new anti-malaria drug.

The research was published this week in Nature Communications.