Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Activation against Malaria

10.08.2010
Facile Oxidation of Leucomethylene Blue and Dihydroflavins by Artemisinins

In combination therapies against malaria, artemisinins are currently the most effective drugs used. Although the subject of intense research for many years, artemisinin's molecular mechanism of action remains a topic of debate.

A much clearer picture of how this compound class works would provide crucial information in the effort to create more effective antimalarial drugs that are less susceptible to resistance. A conventional model suggests that artemisinin elicits its effects through the formation of heme-derived FeII and C-centered radicals. However, a research project led by Richard K. Haynes and Diego Monti has provided strong evidence to counter this model, and their results are reported in the journal ChemMedChem.

"Our research reveals completely new chemistry that includes the formation of unexpected products and which is coherent with relevant enzyme assays," says Haynes. "It directs the science away from the FeII activation theory that is universally held to underpin the antimalarial action of artemisinins. The lead into this work was the use of methylene blue (MB) as an antimalarial drug and the synergistic effect it displays with artemisinins. This is compatible with the idea that artemisinins, like MB, are redox-active molecules that interfere with redox enzymes important for the malaria parasite. MB is converted by reduced flavin cofactors into leucomethylene blue, which initiates a redox cycle involving molecular oxygen. We therefore examined the behavior of such reduced cofactors and model compounds with artemisinins. Importantly, we were able to generate the reduced cofactors catalytically in neutral aqueous (biologically relevant) buffer in the presence of artemisinin and biological reductants, the latter of which alone do not affect the artemisinins. In this sense, our work differs from virtually every other chemical/mechanistic study that has been carried out to date. We report that artemisinins are able to undergo both one-electron transfer and two-electron reduction, and both sets of reactions must have biological consequences."

As for the next step in this project, Haynes and Monti indicate that "Whilst we have not yet tried to pinpoint the flavin cofactor of any particular intra-parasitic enzyme that may be targeted, it is apparent that several flavoenzymes are susceptible to artemisinins. Detailed biochemical and kinetic investigations are being conducted in follow-up studies."

Author: Richard K. Haynes, The Hong Kong University of Science and Technology (China), http://www-chem.ust.hk/Faculty%20staff/Haynes/content.htm

Title: Facile Oxidation of Leucomethylene Blue and Dihydroflavins by Artemisinins: Relationship with Flavoenzyme Function and Antimalarial Mechanism of Action

ChemMedChem 2010, 5, No. 8, 1282–1299, Permalink to the article: http://dx.doi.org/10.1002/cmdc.201000225

Richard K. Haynes | Wiley-VCH
Further information:
http://www.chemmedchem.org
http://www-chem.ust.hk/Faculty%20staff/Haynes/content.htm

More articles from Life Sciences:

nachricht Zap! Graphene is bad news for bacteria
23.05.2017 | Rice University

nachricht Discovery of an alga's 'dictionary of genes' could lead to advances in biofuels, medicine
23.05.2017 | University of California - Los Angeles

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

 
Latest News

Scientists propose synestia, a new type of planetary object

23.05.2017 | Physics and Astronomy

Zap! Graphene is bad news for bacteria

23.05.2017 | Life Sciences

Medical gamma-ray camera is now palm-sized

23.05.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>