Synthesis and preparation of a controlled release system of synthetic alkaloids against malaria

“In recent years, the research group Nucleus for Research in Biological Chemistry at UFSJ (NQBio), has been working with the synthesis and evaluation of the antimalarial activity of new compounds derived from alkaloids, in particular from the class of 3-alkylpyridine marine alkaloids( 3-APA)6. Among the various 3-APA analogues that were synthesized over the years, it was found that those with the best in vitro antiplasmodial activity were those in which a halogen atom (fluorine or chlorine) was introduced at the end of its alkyl chain. The IC50 values recorded against P. falciparum ranged from 2.5 to 7.2 µM and the selectivity index value ranged from 11 to 35 times. These compounds also showed promise in terms of safety with regard to their mutagenic and genotoxic activity7,8. However, the preparation of these 3-APA analogues involves 6 synthetic steps and the yield of the final products ranges from 11-16% yield, which makes it difficult to scale up the synthesis to carry out in vivo assays. Based on the previous experience that has been already acquired working with these alkaloids, it was chosen to perform the synthesis of β-carboline and tetraido-β-carboline derivatives, evaluate the antimalarial activity, study the mechanism of action of these compounds and prepare them in a liposomal formulation. The study of the antiplasmodial potential of β-carboline alkaloids in relation to 3-APA analogues presents some advantages such as reduced number of synthesis steps and better yields. 

Project details

Basic Science
Drug-based Strategies

Mar 2022

Brazil