Investigation of antimalarial activity and molecular targets of natural compounds identified by chemoinformatics against Plasmodium vivax

Abstract

Malaria remains a public health issue, with about 219 million cases registered globally in 2017. Alongside with Venezuela, Brazil still accounts for most of the disease cases in the Americas. Among the species able to infect humans, P. Vivax is responsible for almost all cases in Brazil and presents more and more severe cases, breaking the paradigm of Vivax Malaria as a benign infection. Parasite strains resistant to chloroquine already circulate in endemic areas and therefore there is a need to search for new antimalarial drugs, especially against Vivax Malaria. Regions such as the Amazon - endemic to Malaria- are rich in biodiversity and therefore harbor potential bioactive compounds. Natural products are part of the development process of one third of the drugs introduced in the market in the last thirty years. Hence, as an abundant and diverse source of chemical structures with biological activity, natural products share the pharmacophoric characteristics and are a rich source of scaffolds for medicinal chemistry. Facing drug discovery, the computer-aided drug design optimizes the identification of drug candidate bioactive molecules, including potential antimalarials, reducing the burden of phenotypic screening trials and increasing the chances of success. Thus, combining chemoinformatics and experimental strategies, this project aims to perform ligand-based in silico screenings for the identification and later experimental validation of natural and synthetic compounds with potential antimalarial activity, seeking to identify the molecular targets for the more promising compounds. Thus, we sought to cooperate with knowledge availability and new treatments for the control of Vivax Malaria. (AU)