Phenotypic analysis of a compound derived from the bacterium Rapidithrix thailandica as an antimalarial candidate

Malaria is a disease caused by protozoa of the genus Plasmodium spp., being one of the main public health problems in the world. This disease is endemic in tropical and subtropical regions of the world, and approximately half of the world’s population is exposed to malaria transmission in risk areas. The emergence of cases of resistance to available drugs makes the development of new chemotherapy agents against the disease extremely important.

This class of compounds was synthesized from the molecular structure of marinoquinolines derived from the marine bacterium Rapidithrix thailandica. To this end, MQ22 will be evaluated in standardized tests using in vitro, ex vivo and in vivo models. The molecule will be tested on a panel of P. falciparum strains resistant and sensitive to antimalarials using the SYBr Green assay. Furthermore, the time of action and stage of action will be determined in relation to the morphologies of the parasite, such as ring/trophozoite and schizont. The compound’s ability to generate resistant strains in vitro will be determined by the Minimum Inoculum Resistance (MIR) assay. The possibility of the compound acting on the digestive vacuole will be evaluated with fluorescence assays using the marker Acridine Orange (AO) with changes in the ionic homeostasis of the organelle with the parasite intact. The project will also evaluate whether this compound is active against field isolates of P. vivax and P. falciparum circulating in the Brazilian Amazon. The antimalarial activity of the compound will be confirmed in an in vivo experimental model, using mice infected by P. berghei. The validation of this compound as an antimalarial potential could represent a promising alternative for the treatment of parasites resistant to currently used antimalarials.

Project details

Drug Resistance
Drug-based Strategies
Product Development

Nov 2023 — Oct 2025

Brazil