New compounds for treating tuberculosis and malaria

Jan 23 2008

University of Navarra PhD in chemistry researcher, Esther Vicente, has discovered new compounds active for treating tuberculosis and malaria.

Her thesis, defended at the Faculty of Sciences in her home city of Pamplona, the capital of Navarre, describes the synthesis and characterisation of 65 derivatives of quinoxaline, the structure of which is similar to a number of antimalalarial and antituberculosis pharmaceutical drugs currently on the market. Of the molecules prepared, four stand out for their antimalalarial activity and 15 for their antituberculosis activity.

Ms Vicente's work is within the framework of the line of research of the Medicines R+D Unit at this university, which studies new pharmaceutical drugs to combat forgotten diseases. It involves infectious pathologies that mainly affect developing countries and cause 35,000 deaths daily. Amongst these ailments are tuberculosis and malaria, being the infectious diseases in the world that kill most people – 3 million every year.

The synthesis and characterisation of the new compounds was undertaken at the Centro de Investigación de Farmacobiología Aplicada (CIFA) of the University of Navarra. Esther Vicente did research for five months at the London School of Hygiene and Tropical Medicine in the UK, where she drew up the evaluation of the antimalarial activity of her products. The antituberculosis work was carried out at the Southern Research Institute of Birmingham, within the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) that is subsidised by the National Institute of Allergy and Infectious Diseases in Bethesda (USA).

Studies continuing in London and the USA

Amongst the conclusions of this European PhD, the author emphasises the discovery of new molecules that are more active in vitro than chloroquine, the reference pharmaceutical drug for the treatment of malaria the causing parasite of which has developed resistances. Amongst these molecules four stand out – the most selective – and these continue to be studied in vivo at the London School of Hygiene and Tropical Medicine.

Also, the important in vitro antituberculosis work, under cytotoxicity and good selectivity of fifteen of these molecules, make them new leader compounds in the TAACF programme; thus, in-depth studies are being carried out on them at the University of Illinois and at the Colorado State University, both in the USA.

In her thesis Esther Vicente also describes a Computational Chemistry study which she drew up at the Instituto de Investigación en Fisicoquímica Teórica y Aplicada (INIFTA) in La Plata, Argentina. Here, using various computer programmes, she designed a theoretical model to estimate if a compound could be potentially active, a tool that could prove to be highly useful in the design of new structures active against forgotten diseases.