Hybrid drug use prevents malarial resistance

Scientists from the National University of Singapore have developed a new drug to combat the rise of drug-resistant malaria. Artemisinin-based combined therapies (ACTs) are used to prevent resistance of the malarial parasite to artemisinin. However since last year cases of ACT resistance have been confirmed in Southeast Asia. In addition to this, cases have emerged of malaria resistant to a large number of other drugs along the Thailand-Cambodia border.

The exact mechanism by which artemisinin works is not precisely known, however, chloroquine – another antimalarial drug – works by targeting the digestive vacuole of the Plasmodium single cell parasite. Once it enters what can be described as the parasite’s ‘stomach’, the drug is trapped by a membrane and high levels of the drug kill the parasite. However, mutations of the parasite mean some vacuoles are able to allow chloroquine to be excreted through the membrane, avoiding death.

Associate Professors Kevin Tan and Brian Dymock have developed a drug that combines chloroquine and a chemoreversal agent. The chemoreversal agent ensures the chloroquine stays inside the parasite’s vacuole, reaching high enough levels to kill the parasite. The new drug was three times more effective at killing resistant malaria strains than chloroquine alone and was also effective against ACT–resistant malaria.

This single novel molecule also has many other advantages, notably being easier to take, less risk of drug-drug interactions and may possibly be better absorbed and distributed in the body. The research was published in Antimicrobial Agents and Chemotherapy.