“Novel chemical compounds with anti-malarial activity represent a potent tool in the process of developing new drugs to treat this disease,” Dr. Phillips said.
The study, done in collaboration with Dr. Kiplin Guy of St. Jude Children’s Research Hospital in Memphis and other researchers, started with a “library” of 309,474 chemical compounds.
The researchers used a technique called high throughput screening, which allowed them to test thousands of compounds quickly to identify those with anti-malarial action.
“In addition, publishing the full set of identified compounds will maximize the chances for the most-promising candidates to move into large-scale drug development programs,” Dr. Phillips said.
The screen identified 1,152 compounds that killed the parasite. The researchers then followed up with further tests to determine the mechanism of action of the identified compounds, where possible.
Dr. Phillips and her group tested whether any of the identified compounds killed malaria parasites by inhibiting an enzyme necessary to make pyrimidine, an intermediate molecule for creating DNA. She discovered that three of the library’s compounds with anti-malarial activity blocked this enzyme. Two of those had similar chemical structures to a class of known compounds that she and her colleagues have been studying for possible drug development. The third compound previously was not known to target the enzyme.
“It looked very different from anything we knew about before,” she said.
Having a variety of anti-malarial drugs with different chemical structures and modes of action is important because different types of drugs are given together to slow the parasite from developing resistance, Dr. Phillips said.
In all, the researchers from the various centers found 172 compounds that are “reasonable starting points” for development of new types of drugs.
“We call the identified candidates ‘hits,’ but if any of them are going to become drugs, they’re going to have to undergo chemical modification,” Dr. Phillips said. “For instance, they may need to be altered chemically to enter the cell more easily, or to improve their pharmacology so they will be more effective in people.”
Farah El Mazouni, senior research associate in pharmacology at UT Southwestern, also participated in this study. In addition, the researchers used the UT Southwestern High Throughput System resource in the Department of Biochemistry.
Other participating researchers were from St. Jude Children’s Research Hospital; Griffith University in Australia; the University of Washington, Seattle; the University of Pennsylvania; GlaxoSmithKline; the University of California, San Francisco; Johns Hopkins Bloomberg School of Public Health; the University of Pittsburgh; Medicines for Malaria Venture, Switzerland; the Portland VA Medical Center; and Rutgers, The State University of New Jersey.
The study was funded by the National Institutes of Health, the Welch Foundation, the Medicines for Malaria Venture and other organizations.Media Contact: Aline McKenzie
Aline McKenzie | EurekAlert!
The big clean up after stress
25.05.2018 | Julius-Maximilians-Universität Würzburg
Complementing conventional antibiotics
24.05.2018 | Goethe-Universität Frankfurt am Main
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
24.05.2018 | Ecology, The Environment and Conservation
24.05.2018 | Medical Engineering
24.05.2018 | Physics and Astronomy