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 Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>