Synthesis of new marinoquinoline derivatives with potential antimalarial activity

• Grant number: 22/03731-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2022
• End date: June 30, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Carlos Roque Duarte Correia
• Grantee: Wellington da Silva
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/25770-6 - New frontiers in cross-coupling reactions promoted by palladium: combining enantioselective catalysis, C-H activations, new materials and in flux reactions aiming at high efficiency and sustainability in synthetic processes, AP.TEM
• Associated scholarship(s): 23/03295-3 - Synthesis of new marinoquinoline derivatives with potential antimalarial activity and determination of their molecular target, BE.EP.DR

Abstract

Malaria is a disease caused by species of the parasite Plasmodium spp, which is transmitted to humans through the bite of the female Anopheles mosquito, when infected by Plasmodium. According to the World Health Organization (WHO), in 2020 alone, malaria caused the death of 627,000 people. There are currently several drugs available on the market for the treatment of malaria, however, the parasites are gaining resistance to them, thus making the treatment ineffective. In addition, the only vaccine currently available (RTS,S/AS01) is not effective against all species of the parasite. Therefore, it is extremely urgent to develop new drugs capable of efficiently combating this disease. In this context of new drug discovery, a class of compounds called marinoquinolines (MQs) have been gaining prominence due to their inhibitory activities against Plasmodium. With that, it is proposed in this project to synthesize and characterize several MQs, which will be obtained from 9 to 10 reaction steps, starting from pyrrole and 4-methoxy-2-nitroaniline. Then, these substances will be submitted to in vitro evaluation against P. falciparum, in collaboration with Prof. Dr. Rafael Victorio Carvalho Guido, from the São Carlos Institute of Physics, University of São Paulo, and with these results, a structure-activity relationship (SAR) study of this class of substances will be carried out, which will allow the identification of prototype substances for future evaluations of mechanism of action and other more advanced tests.