Nineteen Authors, Six Laboratories, Three Continents and the Development of a Synthetic Antimalarial Candidate. (August 19, 2004)

    Led by the University of Nebraska's Jonathan Vennerstrom a team of 19 including four from Australia's Victorian College of Pharmacy at Monash University have developed a cheap, rapidly effective synthetic candidate drug using the Chinese herbal medicine artemisinin as a template.

 The team that performed the tour de force consisted of chemists, parasitologists, pharmacokineticists and toxicologists. Their starting point for performing their syntheses were a group of potentially active but highly unstable compounds. Through a series of sophisticated syntheses the chemical grouping that possessed antimalarial activity was first protected from degradation. The next step was to increase the compounds' water solubility so that they could be more easily absorbed from the gastrointestinal tract. After testing a number of compounds with potential, candidate OZ277 was singled out because as Nature reports, it was "well absorbed when administered orally to animals, and had outstanding antimalarial properties both in vitro and in vivo. Unlike the available artemisinin derivatives, OZ277 is structurally simple and its synthesis can be scaled up in a way that is economically feasible. What's more, its toxicological profiles are satisfactory. Following the development of a large-scale synthesis for OZ277, it has just entered 'first into man' studies."

The precise mechanism behind its activity is unknown but it is suggested that it reacts with part of the red blood cell's haemoglobin to form toxic, carbon-centred free radicals which may fatally alter key proteins of the malarial parasite.

The development of OZ277 is a flagship project for the Medicines for Malaria Venture, a non-profit organization established as a Foundation in Geneva, Switzerland, and launched in November 1999. It was created to "discover, develop and deliver new affordable antimalarial drugs through effective public-private partnerships."

This transcontinental multidisciplinary effort to develop OZ277 included participants from:

The College of Pharmacy, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska, USA;
Fulcrum Pharma Developments Ltd, Hemel Hempstead, Hertfordshire, UK;
The Swiss Tropical Institute, Basel, Switzerland;
The Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia;
F. Hoffmann-La Roche Ltd, Basel, Switzerland, and
Basilea Pharmaceutica Ltd, Basel, Switzerland.

For those with subscriptions to Nature see Identification of an antimalarial synthetic trioxolane drug development candidate.