Synthesis of new marinoquinoline derivatives with potential antimalarial activity and determination of their molecular target

• Grant number: 23/03295-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: July 01, 2023
• End date: June 30, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Carlos Roque Duarte Correia
• Grantee: Wellington da Silva
• Supervisor: Matthew Todd
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University College London (UCL), England
• Associated to the scholarship: 22/03731-5 - Synthesis of new marinoquinoline derivatives with potential antimalarial activity, BP.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 with Plasmodium. According to the World Health Organization (WHO), in 2020 alone, malaria caused the deaths of 627,000 people. Currently, there are several drugs available on the market for the treatment of malaria, however, the parasites are gaining resistance to them, thus making the treatment ineffective. Furthermore, the only currently available vaccine (RTS,S/AS01) is not effective against all parasite species. Therefore, the development of new drugs capable of efficiently combating this disease is extremely urgent. In this context of new drug discovery, a class of compounds called marinoquinolines (MQs) has been gaining prominence due to their inhibitory activities against Plasmodium. Therefore, this project proposes to synthesize and characterize several MQs, derived from the most potent MQ already discovered by the group of professor Correia. The proposed synthetic pathway involves 9 to 10 reaction steps, starting from pyrrole and 4-methoxy-2-nitroaniline. The new marinoquinolines will be then submitted to in vitro evaluation against P. falciparum. Another objective of the project is to understand the mode of action of marinoquinolines, identifying the target of these compounds. With the target in hand, a molecular modeling study will be carried out to identify new potential structures, which will then be synthesized and evaluated against P. falciparum. (AU)