4-quinolinone derivatives as candidates for antimalarial drugs: characterization of Antiplasmodial activity in vitro, in vivo and mode of action

Malaria, a tropical disease caused by protozoa of the genus Plasmodium, continues to be a major cause of mortality, especially in children under five years of age, generating socioeconomic problems in world populations in endemic regions. The transmission of the disease occurs in 91 countries, and is endemic in tropical and subtropical regions of Africa, Southeast Asia and Latin America. Almost half of the world’s population (3.2 billion people) is exposed to malaria transmission in risk areas. In 2016, 216 million cases and 445,000 deaths were recorded, most of them in the sub-Saharan region of the African continent. In recent decades worldwide efforts to eradicate malaria have caused a marked reduction in the number of cases, however the emergence and dissemination of parasites resistant to available drugs makes the search for new chemotherapeutic agents against the disease extremely important. In this sense, cell biology and parasitology studies will be carried out, as well as medicinal chemistry. The derivatives studied will be evaluated in in vitro and in vivo growth inhibition assays against strains sensitive and resistant to conventional antimalarials. Complementarily, cytotoxicity and hemolytic activity tests will be applied to determine the toxicological profile of the series. A study of the structure-activity relationship of the series will also be done. Preliminary results indicated promising antiplasmodial activity of 4-quinolinone and acridone derivatives against Plasmodium falciparum in vitro. The works to be developed in this Master’s project will complement the experience obtained in the development of the candidate’s scientific initiation project, and will add knowledge of new techniques, in the context of the application of experimental methods for the discovery of new candidates for antimalarial drugs. Physics of São Carlos – USP houses laboratories with vast experience in medicinal chemistry, consecrated by the creation of the Center for Research and Innovation in Biodiversity and Pharmaceuticals (CIBFar-CEPID), and provides adequate facilities and equipment for the process of searching for new drug candidates , aggregating all the fundamental factors for the realization of the proposed project. In addition, the group is part of the group of associated laboratories of the non-profit organization Medicines for Malaria Venture (MMV), acting as a Center for Screening and Evaluation of Antimalarial Drug Candidates. In view of this, the CIBFar-CEPID laboratories have the infrastructure to carry out this research project in its entirety. 

Project details

Basic Science
Drug-based Strategies
Enabling Technologies & Assays

Apr 2018 — Nov 2019

Brazil