Discovery of 4-quinolinones derivatives as lead compound candidates for the development of new antimalarials

• Grant number: 17/04070-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2017
• End date: December 31, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Rafael Victorio Carvalho Guido
• Grantee: Juliana Oliveira de Souza
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

Malaria, caused by protozoa parasite of the genus Plasmodium, is one of the world's leading public health problems. The disease occurs in 91 countries, being endemic in the tropical and subtropical regions of Africa, Southeast Asia and Latin America. Nearly half the world's population (3 billion people) is exposed to malaria transmission in high-risk areas. In 2015, 212 million cases and 429 thousand deaths were registered, most of them in Africa (WHO, 2016). The emergence of cases of resistance to available drugs makes the development of new chemotherapeutic agents against the disease extremely important. The aim of this research project is the discovery and development of 4-quinolinone derivatives as lead compound candidates for the development of new antimalarial drugs. To that end, studies of cellular biology and parasitology will be employed. The compounds will be evaluated in standardized biological assays against susceptible and drug resistant strains available. In addition, cytotoxicity assays will be performed for the determination of the toxicological profile of the compounds. Preliminary results indicated that 4-quinolinone derivatives are promising inhibitors of Plasmodium falciparum in vitro. The work to be carried out in this Scientific Initiation project will be of extreme value for the scientific training of the candidate regarding the use of experimental methods for the discovery of new antimalarial drug candidates. The Institute of Physics of São Carlos - USP has world-renowned experience in medicinal chemistry, which was reinforced by the creation of the Center for Research and Innovation in Biodiversity and Pharmaceuticals (CIBFar-CEPID), providing modern facilities for the discovery of new drug candidates. In addition, the group is part of the network of partner laboratories of the non-profit organization Medicine for Malaria Venture (MMV) as a Center of Screening and Evaluation for Antimalarial Drug Candidates. Therefore, the laboratories of CIBFar-CEPID have complete infrastructure to carry out all the steps proposed in this research project. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GONRING-SALARINI, KARLA L.; CONTI, RAPHAEL; DE ANDRADE, JEAN PAULO; BORGES, BARBARA JULIANA P.; AGUIAR, ANNA CAROLINE C.; DE SOUZA, JULIANA O.; ZANINI, CAMILA L.; OLIVA, GLAUCIUS; TENORIO, JUAN CARLOS; ELLENA, JAVIER; et al. In vitro Antiplasmodial Activities of Alkaloids Isolated from Roots of Worsleya procera (Lem.) Traub (Amaryllidaceae). Journal of the Brazilian Chemical Society, v. 30, n. 8, p. 1624-1633, AUG 2019. (15/18192-9, 13/07600-3, 17/04070-4)