Phenotypical Analysis of a compound derived from the marine bacteria Rapidithrix thailandica as an antimalaric candidate

• Grant number: 23/09653-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2023
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Anna Caroline Campos Aguiar
• Grantee: Caio Silva Moura
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated research grant: 19/19708-0 - Identification of new antimalarial compounds: a multidisciplinary strategy aimed to search for potent chemical classes against new molecular targets and different stages of life of Plasmodium spp, AP.JP

Abstract

Malaria is a disease caused by protozoa of the genus Plasmodium spp. and is one of the world's leading public health problems.one of the main public health problems in the world. This disease is endemic in tropical and subtropicaltropical and subtropical regions of the globe, and about half of the world's population is exposed to malaria transmission in risk areas.malaria transmission in areas at risk. The emergence of cases of resistance to available drugsavailable drugs makes the development of new chemotherapeuticagents against the disease.The proposed research project aims to elucidate the possible effects on the parasite'sphenotype associated with the use of a compound of the quinoline class called MQ22.This class of compounds was synthesized from the molecular structure ofmarinoquinolines derived from the marine bacterium Rapidithrix thailandica. To this end, MQ22,will be evaluated in standardized assays using in vitro, ex vivo and in vivo models. Amolecule will be tested on a panel of P. falciparum strains resistant and sensitive to antimalarials using theantimalarials using the SYBr Green assay. In addition, the time ofaction and the stage of action against parasite morphologies such as ring/trophozoite and schizont will be determined.The ability of the compound to generate resistant strains in vitro will be determined by the assay ofMinimum inoculum resistance (MIR) assay. The ability of the compound to act in the digestive vacuole,will be evaluated with fluorescence assays using the marker Acridine Orange (AO) withalteration of the ionic homeostasis of the organelle with the parasite intact. We will assess whether thisactive against field isolates of P. vivax and P. falciparum circulating in the Brazilian Amazon.Brazilian Amazon. The antimalarial activity of the compound will be confirmed in an in vivo experimental model usingvivo experimental model using P. berghei infected mice. The validation of this compound asantimalarial potential, may represent a promising alternative for the treatment of antimalarial-resistantof parasites resistant to currently used antimalarials.