Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Modified bone drug kills malaria parasite in mice

28.02.2012
A chemically altered osteoporosis drug may be useful in fighting malaria, researchers report in a new study.

Unlike similar compounds tested against many other parasitic protozoa, the drug readily crosses into the red blood cells of malaria-infected mice and kills the malaria parasite. The drug works at very low concentrations with no observed toxicity to the mouse.

The study appears in the Proceedings of the National Academy of Sciences.
The researchers found the drug by screening a library of about 1,000 compounds used in previous efforts to target an important biochemical pathway (called isoprenoid biosynthesis) in cancer and in disease-causing organisms. The new drug lead, BPH-703, inhibits a key enzyme in isoprenoid biosynthesis that enables the malaria parasite to sustain itself and defend itself from the host immune system. The drug has little effect on the same chemical pathway in human or mouse cells, said University of Illinois chemistry professor Eric Oldfield, who led the study.
The lead compounds are chemically modified forms of the osteoporosis drugs Actonel (Risedronate) and Zometa (Zoledronate), Oldfield said. Risedronate and Zoledronate potently block isoprenoid biosynthesis, but are unable to get across the membrane of red blood cells to get to the parasite. The modified forms include a long lipid tail that helps them pass through the lipid-rich membrane of red blood cells, and also enhances the drug’s ability to bind to the target enzyme, geranylgeranyl diphosphate synthase (GGPPS), he said.

“We found that compounds that were really active had a very long hydrocarbon chain,” Oldfield said. “These compounds can cross the cell membrane and work at very low concentrations.”

The World Health Organization estimates that malaria killed 708,000 to 1.003 million people in 2008, most of them in Sub-Saharan Africa and Asia. The malaria parasite has evolved resistance to nearly every drug used so far to combat it, and while some of these drugs still work – especially when used in combination – drug-resistant malaria strains are always emerging.

“It’s important to find new drug targets because malaria drugs last only a few years, maybe 10 years, before you start to get resistance,” Oldfield said. “The parasites mutate and then you lose your malaria drug.”

“We are the first to show that the enzyme GGPPS is a valid target for malaria,” said study co-author Yonghui Zhang, a research scientist in Oldfield’s lab and inventor of the lead compound, BPH-703. “Our work gives a new direction to find new antimalarial drugs.”

Editor’s notes: To reach Eric Oldfield, call: 217-333-3374;
email eoldfiel@illinois.edu.
The paper, “Lipophilic analogs of zoledronate and risedronate inhibit Plasmodium GGPPS and exhibit potent anti-malarial activity,” is available from the U. of I. News Bureau.

Diana Yates | University of Illinois
Further information:
http://www.illinois.edu

More articles from Life Sciences:

nachricht Nanocages in the lab and in the computer: how DNA-based dendrimers transport nanoparticles
19.10.2018 | University of Vienna

nachricht Less animal experiments on the horizon: Multi-organ chip awarded
19.10.2018 | Fraunhofer-Institut für Werkstoff- und Strahltechnik IWS

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Goodbye, silicon? On the way to new electronic materials with metal-organic networks

Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz (Germany) together with scientists from Dresden, Leipzig, Sofia (Bulgaria) and Madrid (Spain) have now developed and characterized a novel, metal-organic material which displays electrical properties mimicking those of highly crystalline silicon. The material which can easily be fabricated at room temperature could serve as a replacement for expensive conventional inorganic materials used in optoelectronics.

Silicon, a so called semiconductor, is currently widely employed for the development of components such as solar cells, LEDs or computer chips. High purity...

Im Focus: Storage & Transport of highly volatile Gases made safer & cheaper by the use of “Kinetic Trapping"

Augsburg chemists present a new technology for compressing, storing and transporting highly volatile gases in porous frameworks/New prospects for gas-powered vehicles

Storage of highly volatile gases has always been a major technological challenge, not least for use in the automotive sector, for, for example, methane or...

Im Focus: Disrupting crystalline order to restore superfluidity

When we put water in a freezer, water molecules crystallize and form ice. This change from one phase of matter to another is called a phase transition. While this transition, and countless others that occur in nature, typically takes place at the same fixed conditions, such as the freezing point, one can ask how it can be influenced in a controlled way.

We are all familiar with such control of the freezing transition, as it is an essential ingredient in the art of making a sorbet or a slushy. To make a cold...

Im Focus: Micro energy harvesters for the Internet of Things

Fraunhofer IWS Dresden scientists print electronic layers with polymer ink

Thin organic layers provide machines and equipment with new functions. They enable, for example, tiny energy recuperators. In future, these will be installed...

Im Focus: Dynamik einzelner Proteine

Neue Messmethode erlaubt es Forschenden, die Bewegung von Molekülen lange und genau zu verfolgen

Das Zusammenspiel aus Struktur und Dynamik bestimmt die Funktion von Proteinen, den molekularen Werkzeugen der Zelle. Durch Fortschritte in der...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Conference to pave the way for new therapies

17.10.2018 | Event News

Berlin5GWeek: Private industrial networks and temporary 5G connectivity islands

16.10.2018 | Event News

5th International Conference on Cellular Materials (CellMAT), Scientific Programme online

02.10.2018 | Event News

 
Latest News

Nanocages in the lab and in the computer: how DNA-based dendrimers transport nanoparticles

19.10.2018 | Life Sciences

Thin films from Braunschweig on the way to Mercury

19.10.2018 | Physics and Astronomy

App-App-Hooray! - Innovative Kits for AR Applications

19.10.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>