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:4/26/2016)... Research and Markets has announced ... 2016-2020"  report to their offering.  , ,     (Logo: ... analysts forecast the global multimodal biometrics market to ... period 2016-2020.  Multimodal biometrics is being ... the healthcare, BFSI, transportation, automotive, and government for ...
(Date:4/15/2016)... -- Research and Markets has announced the ...  report to their offering.  ,      ... gait biometrics market is expected to grow at ... Gait analysis generates multiple variables such ... compute factors that are not or cannot be ...
(Date:3/31/2016)... , March 31, 2016 ... ) ("LegacyXChange" or the "Company") LegacyXChange is ... users of its soon to be launched online site ... https://www.youtube.com/channel/UCyTLBzmZogV1y2D6bDkBX5g ) will also provide potential shareholders ... of DNA technology to an industry that is notorious ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... GUELPH, ON , June 27, 2016 /PRNewswire/ - BIOREM ... it has been advised by its major shareholders, Clean ... LP, United States based venture ... common shares of Biorem (on a fully diluted, as ... for the disposition of their entire equity holdings in ...
(Date:6/27/2016)... ... June 27, 2016 , ... ... Amgen, will join the faculty of the University of North Carolina Kenan-Flagler ... of strategy and entrepreneurship at UNC Kenan-Flagler, with a focus on the school’s ...
(Date:6/24/2016)... ... , ... While the majority of commercial spectrophotometers and fluorometers use the z-dimension ... are higher end machines that use the more unconventional z-dimension of 20mm. Z-dimension ... bottom of the cuvette holder. , FireflySci has developed several Agilent flow cell ...
(Date:6/23/2016)... /PRNewswire/ - FACIT has announced the creation of ... company, Propellon Therapeutics Inc. ("Propellon" or "the Company"), ... portfolio of first-in-class WDR5 inhibitors for the treatment ... represent an exciting class of therapies, possessing the ... cancer patients. Substantial advances have been achieved with ...
Breaking Biology Technology: