Dendrimeric prodrugs potentially active in malaria: Synthesis and evaluation of biological activity

Malaria is a potentially fatal disease caused by parasites of the genus Plasmodium. Despite advances, there are barriers to its total eradication, highlighting the growing resistance to antimalarials, as well as repellents against mosquitoes of the genus Anopheles, vectors of the disease. The infection caused by P. falciparum is the most serious form, with the highest number of deaths, known then as “severe” or “malignant” malaria. Among the clinical manifestations is the Acute Respiratory Distress Syndrome (ARDS), which is a reflection of the extensive inflammatory response caused by the parasite. Artesunate has recently been shown to have anti-inflammatory activity in several organs, including the lungs. Therefore, the potential of this compound in ARDS stands out. The mechanism of action is related to the ability to decrease vascular permeability in animals, also reducing the effects of ARDS through the inactivation of pro-inflammatory proteins. Dendrimeric prodrugs, on the other hand, can be useful to decrease toxicity, improve the therapeutic index, as well as solubility, in addition to creating a slow release profile of the prototype. The compound will be formed by the coupling of artesunate with the PAMAM-G1 derivative. The contribution of Prof. doctor Jørn B. Christensen from the University of Copenhagen, who specializes in dendrimer synthesis and will send us PAMAM-G1. The biological assays will be done in collaboration with Profa. Dr. Sabrina Epiphanio, from the Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, USP. Therefore, it is considered that the present proposal contributes, in an innovative way, with the advance in the discovery of potential compounds for the treatment of the Acute Respiratory Syndrome observed in patients with severe malaria.

Project details

Basic Science
Drug-based Strategies

Feb 2020

Brazil