Discovery of new antimalarial drugs with unique properties using an innovative technology
8 September 2016
Currently, only a limited number of drug have known activity against malaria and in addition drug resistance is emerging. Scientists have developed an innovative method to identify new compounds that target malaria.
The malaria parasite has many manifestations. The currently available drugs are mainly directed against the parasitic stage that is present in the blood and thereby causes disease. However, these drugs are not suitable for the prevention of infection and do not inhibit parasite transmission.
In the search for a compound that does have activity against all life cycle stages of the parasite an innovative technology was developed. Inspired by the complexe structures and diversity found in natural compounds, compounds with similar characteristics were synthesized in the lab.
This led to the discovery of compounds with a new mode of action. The activity of these agents against a wide variety of malaria species and developmental stages of the parasite the compounds was tested in different malaria models systems in a large number of labs. The BPRC has developed an in vitro assay in which the activity of drugs against developing liver parasites, but also against dormant forms, so-called hypnozoites, can be tested (http://www.bprc.nl/en/article/a-new-method-for-testing-the-activity-of-drugs-against-dormant-malaria-parasites). The compounds proved to be active in this system.
Activity against many other developmental forms of the malaria parasite was also shown. In mice, one dosage of this class of compounds was already sufficient to cure malaria. This innovative way of designing compounds can therefore lead to the identification of new classes of drugs with unique properties. This study which is the result of a large collaboration between different labs, including the BPRC, has been published in the leading scientific journal Nature (http://www.nature.com/nature/journal/vaap/ncurrent/full/nature19804.html).