Original antimicrobial compounds as new therapeutic alternatives to control chemoresistant Plasmodium spp: validation of multistage antimalarial activity and investigation of mode of action

• Grant number: 23/12812-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2024
• End date: March 31, 2028
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Fabio Trindade Maranhão Costa
• Grantee: Emily Thays da Silva Rodrigues
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/18611-7 - Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax, AP.TEM

Abstract

Among parasitic diseases with endemic behavior, malaria is the one that poses major challenges for its control and treatment, presenting around 247 million cases around the globe in 2021 and being prevalent in countries facing socio-economic complexities. This disease is caused by a protozoan of the genus Plasmodium spp, with P. vivax as the one responsible for most cases in Brazil. Even though chloroquine has been the treatment adopted in most regions, the dissemination of parasite strains resistant to this drug as well as most antimalarial drugs available has highlighted the need for new therapeutic tools. Throughout history, several antimicrobial drugs have been used as malaria treatment, also used in combination with traditional antimalarial therapy. The investigation of antimicrobial agents as an alternative approach represents a source of scaffolds for medical chemistry and the discovery of new potential antiparasitic molecules. Using a combination of in-house experiments and computational analysis of chemical space and structural compatibility, this project aims to trial compounds initially developed for the treatment of bacterial diseases such as tuberculosis and bacteria of the ESKAPE spectra as potential candidates for malaria treatment. While also interrogating their respective modes of action, we aim to identify novel molecular targets for the most promising compounds in a bid to evade cross-resistance phenotypes established in clinical settings.