Navigation Links
Modified bone drug kills malaria parasite in mice
Date:2/27/2012

CHAMPAIGN, Ill. A chemically altered osteoporosis drug may be useful in fighting malaria, researchers report in a new study. Unlike similar compounds tested against 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."


'/>"/>
Contact: Diana Yates, Life Sciences Editor
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

Related biology news :

1. Novel bioreactor enhances interleukin-12 production in genetically modified tobacco plants
2. Modified gene targets cancer cells a thousand times more often than healthy cells
3. Modified plants may yield more biofuel
4. Engineers develop method to disperse chemically modified graphene in organic solvents
5. Weed resistance to glyphosate in genetically modified soybean cultivation in Argentina
6. Genetically-modified mice reveal another mechanism contributing to heart failure
7. NIH stem cell guidelines should be modified, UCSF team reports
8. UT Southwestern researchers use novel sperm stem-cell technique to produce genetically modified rats
9. Genetically modified cell procedure may prove useful in treating kidney failure
10. Scientists find the first evidence of genetically modified plants in the wild
11. Scientists find new evidence of genetically modified plants in the wild
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Modified bone drug kills malaria parasite in mice
(Date:4/11/2017)... April 11, 2017 No two people ... at the New York University Tandon School of ... have found that partial similarities between prints are ... in mobile phones and other electronic devices can ... The vulnerability lies in the fact that fingerprint-based ...
(Date:4/5/2017)... April 5, 2017  The Allen Institute for Cell ... Explorer: a one-of-a-kind portal and dynamic digital window into ... data, the first application of deep learning to create ... cell lines and a growing suite of powerful tools. ... these and future publicly available resources created and shared ...
(Date:4/4/2017)... April 4, 2017   EyeLock LLC , a ... the United States Patent and Trademark Office (USPTO) has ... the linking of an iris image with a face ... represents the company,s 45 th issued patent. ... very timely given the multi-modal biometric capabilities that have ...
Breaking Biology News(10 mins):
(Date:6/20/2017)... , ... June 20, 2017 , ... ... Robbie, PhD, a well-versed leader with extensive assay development and biomarker expertise, as ... Biomedical is a Boston CRO specializing in bio-analytical assay development and sample testing ...
(Date:6/19/2017)... ... 2017 , ... As Vice President, Product Services, Mr. Guinter ... support, and client process and SOP development. , Mr. Guinter brings a wealth ... for service providers and top-tier pharmaceuticals, and as an independent consultant supported a ...
(Date:6/19/2017)... Iowa (PRWEB) , ... June 19, 2017 , ... A ... interplay among its cells and tissues by delivering pollen and nectar containing nutrients necessary ... the means to stay healthy. , Many recent indicators point to a decline in ...
(Date:6/16/2017)... (PRWEB) , ... June 16, 2017 , ... CTNext ... Entrepreneur Innovation Awards (EIA), held at The LOFT at Chelsea Piers in Stamford. , ... ideas to a panel of judges for an opportunity to secure $10,000 awards to ...
Breaking Biology Technology: