New hybrid drug plugs the hole in malaria drug resistance

April 11, 2016, National University of Singapore

A combination of artemisinin and another drug (artemisinin combination therapy, ACT) is currently the best malaria treatment recommended by the World Health Organization. In early 2015, artemisinin-resistant malaria was confirmed in five countries in Southeast Asia: Cambodia, Laos, Myanmar, Thailand, and Vietnam. Even more worrying, malaria cases that are resistant to practically all drugs have begun to emerge along the Thailand-Cambodia border. Such cases do not respond to ACT; thus, new therapies that are effective for resistant malaria are urgently needed.

For a therapy to be effective, it needs to counteract the resistance of to existing drugs. Malaria drugs, such as chloroquine and artemisinin, work within the digestive vacuole of the , which serves as the stomach of the parasite. The killing action of chloroquine is better understood than that for artemisinin. Once chloroquine enters the parasite's "stomach," the stomach membrane traps the drug inside (similar to a window closing and locking) and the high levels of drug can then effectively kill the parasite. However, in a resistant malaria parasite, the stomach membrane is mutated so that it cannot keep the drug inside the stomach, just like a window with a broken lock. Since the drug is no longer concentrated inside the stomach, it can no longer kill the malaria parasite effectively.

Associate Professor Kevin Tan of the Department of Microbiology & Immunology and Associate Professor Brian Dymock of the Drug Development Unit and the Department of Pharmacy have now developed a hybrid drug that combines parts of chloroquine and a chemoreversal agent. This gives the hybrid drug a "dual acting" mechanism: a killing factor (chloroquine-derived) and a second component that acts on that faulty window of the parasite's stomach so it can now close again (the chemoreversal agent). The drug becomes concentrated inside the of the drug-resistant parasite and can kill the parasite.

The new hybrid drug killed malaria strains grown in the laboratory as well as malaria parasites from patients in Thailand. Importantly, the drug was very effective against malaria that was resistant to both chloroquine and artemisinin. It was three times more effective than chloroquine at killing these resistant strains. The researchers are continuing to refine the hybrid drug to make it an even more effective therapy for resistant malaria. This work was published online on March 7, 2016 in the journal Antimicrobial Agents and Chemotherapy.

Although and chemoreversal agents have been used to treat drug-resistant malaria before, this is the first time that a hybrid of and a newly discovered chemoreversal factor has been used in a single novel molecule for this purpose. A single therapy has several advantages that make it a promising new weapon against drug-. Besides being more convenient to take, it has less risk of drug-drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.

Explore further: Less effective antimalarial therapies can help fight malaria better

More information: Aicha Boudhar et al. Overcoming Chloroquine Resistance in Malaria: Design, Synthesis and Structure-Activity Relationships of Novel Hybrid Compounds, Antimicrobial Agents and Chemotherapy. DOI: 10.1128/AAC.02476-15

Related Stories

Less effective antimalarial therapies can help fight malaria better

November 12, 2015
Oxford University scientists have found that the more effective way to beat malaria is to use less effective drugs some of the time.

Drug-resistant malaria could spread to Africa: study

October 20, 2015
A drug-resistant malaria parasite from southeast Asia can infect African mosquitoes, said a study Tuesday, boosting fears that a hard-to-cure variant of the disease could reach the world's most vulnerable continent.

Curbing malaria resistance with multiple therapies

March 29, 2016
In order to preserve first-line drugs for treating malaria, multiple combination therapies should be deployed within a population to prevent resistance from developing, according to Maciej Boni from the Centre for Tropical ...

Factfile on Nobel anti-malaria drug artemisin

October 6, 2015
Today's frontline drug to fight malaria, artemisinin has a history going back many centuries, for it traces its past to ancient Chinese medicine.

New genetic mutation could signal start of malaria drug resistance in Africa

April 17, 2015
Early indicators of the malaria parasite in Africa developing resistance to the most effective drug available have been confirmed, according to new research published in Antimicrobial Agents and Chemotherapy.

Recommended for you

Breakthrough treatment for crippling jaw disease created

June 20, 2018
A first-ever tissue implant to safely treat a common jaw defect, known as temporomandibular joint dysfunction, has been successfully tested by UCI-led researchers in a large animal model, according to new findings.

Cell-free DNA profiling informative way to monitor urinary tract infections

June 20, 2018
Using shotgun DNA sequencing, Cornell University researchers have demonstrated a new method for monitoring urinary tract infections (UTIs) that surpasses traditional methods in providing valuable information about the dynamics ...

New flu vaccine only a little better than traditional shot

June 20, 2018
A newer kind of flu vaccine only worked a little bit better in seniors this past winter than traditional shots, the government reported Wednesday.

Blood signature could improve early tuberculosis diagnosis

June 19, 2018
A gene signature in the bloodstream could reveal whether someone is going to develop active tuberculosis (TB) disease months before symptoms begin. Such a signature has now been developed by a team led by the Francis Crick ...

Scientists uncover a factor important for Zika virus host species restriction

June 19, 2018
Princeton University researchers Qiang Ding, Alexander Ploss, and colleagues have identified one of the mechanisms by which Zika virus (ZIKV) circumvents immune control to replicate in human cells. The paper detailing this ...

Toothpaste and hand wash may contribute to antibiotic resistance

June 19, 2018
A common ingredient in toothpaste and hand wash could be contributing to antibiotic resistance, according to University of Queensland research.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.