A New, Highly Effective and Selective Molecule is Developed to Fight Malaria

Publicado em 10 agosto 2018

SAO PAULO, Brazil - A novel laboratory-synthesized molecule based in natural compounds found in marine gliding bacteria - known as marinoquinolines - is a strong candidate for the development of a new antimalarial drug.

In tests, the molecule proved capable of killing even the strain that resists conventional antimalarials. The molecule displays low toxicity and high selectivity, acting only on the parasite and not on other cells of the host organism.

The molecule was developed in Brazil at the Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar), one of the Research, Innovation and Dissemination Centers (RIDCs) funded by the Sao Paulo Research Foundation - FAPESP. The researchers tested the molecule in strains cultured in vitro as well as in mice using Plasmodium berghei, since mice is immune to infection by Plasmodium falciparum, which causes the most aggressive type of malaria.

"In mice, the number of parasites in the bloodstream (parasitemia) had fallen 62% by the fifth day of the test. After 30 days, all the mice given doses of the molecule were still alive," said Rafael Guido, a professor at the University of Sao Paulo's Sao Carlos Physics Institute (IFSC-USP).

Guido co-authors an article published in the Journal of Medicinal Chemistry, on which the researchers describe the molecule's inhibitory action in the blood and liver stages of the parasite's asexual cycle, which is responsible for the signs and symptoms of the disease.

Potentializing the molecule's pharmacological activity
Marinoquinolines were first isolated from marine gliding bacteria and, when discovered, were evaluated for activity against malariaChagas disease and tuberculosis. However, the natural products exhibited only weak to moderate activity against these pathogens.

"The core of these molecules, known as pyrroloquinoline [which contains 3H-pyrrolo[2,3-c]quinoline], drew our attention. This is a rare structure among natural products and is rarely discussed in the scientific literature," said Carlos Roque Duarte Correia, a professor at the University of Campinas's Chemistry Institute (IQ-UNICAMP) and principal investigator at the FAPESP center.