Induction of heme-based adducts in natural complex matrixes: development of new analytical methodologies in search of antimalarial drugs

Abstract

Malaria is one of the most important infecto-parasitary diseases in the world. More than 90% of this infection occurs in Africa causing more that two million deaths per year. Although Africa in the most castigated tropical country, other such as India and Brazil are also highly endemic. The resistance of Plasmodium falciparum to known drugs, especially chloroquine and the low research funding for research of new alternatives to attack this vector, drastically increases this scenario. The quest for natural products that may block biological processes vital to P. falciparum biological cycle is a rational strategy that is being used in the finding of new chemical prototypes that may destroy the parasite. One particularly interesting target is heme polymerization. In the acid digestive vacuole, hemoglobin is degraded producing toxic heme or hemin, the Plasmodium thus polymerizes this molecule into a crystalline polymeric substance called hemozoin or malaric pigment. The research strategy for this proposal deals with the implementation of an in vitro assay aiming to detect inhibition on heme polymerization. This will be developed and performed in the “Núcleo de Bioensaios, Biossíntese e Ecofisiología de Produtos Naturais – NuBBE” and will be adapted to known sophisticated hyphenated techniques with the solely objective to identify promising antimalarial plant species from the Cerrado and Atlantic Forest and thus contribute with the project “Conservation and sustainable use of the plant diversity from Cerrado and Atlantic Forest: Chemical diversity and prospection for potential drugs, Phase II (FAPESP ID number: 03/02176-7, BIOTA-FAPESP Program), which main goal is the bioprospection of São Paulo State’s plant species. (AU)