Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Malaria is a critical global health problem, with high mortality and morbidity rates, which ultimately hinder socioeconomic development in endemic areas. The evolution of drug resistance in malaria parasites, particularly in the case of Plasmodium falciparum, and the scarcity of effective drugs both for case management and for blocking transmission contribute to the aggravating malaria's burden. The present study sought to evaluate the potential of novel 4-quinolone derivatives as multistage antimalarials with predicted activity against asexual intraerythrocytic, liver, and transmission-blocking stages. We show that compound 1, a natural 2-substituted-4-quinolone, previously isolated from plants and microorganisms, and its derivatives 2 – 6, displayed significant activity against Plasmodium sexual stages in both ex vivo and in vivo assays and effectively prevented hepatic cell infections, with compound 1 displaying the highest activity against both sexual and asexual stages. Collectively, we conclude that these compounds warrant further studies toward the development of new antimalarial drugs.
Source: ACS Omega
Authors: Yasmin Annunciato, Everton M. da Silva, Jéssica E. Araújo, Leandro do N. Martinez, Sofia Santana, Eyob A. Workneh, Luís C. S. Alvarez, Marcela L. Magalhães, Alice Oliveira Andrade, Wallyson de J. da Costa, Guilherme Campolina, Matheus Nascimento Santana, Camila S. Barbosa, Erica P. M. L. Peres, Caio S. Moura, Najara A. C. dos Santos, Alessandra da S. Bastos, Roberto Rudge de M. Barros, Marcos L. Gazarini, Jansen Fernandes Medeiros, Carolina B. G. Teles, Fabio T. M. Costa, Ana C. Alves, Dhelio B. Pereira, João Pinto, Pedro V. L. Cravo, Rafael Victorio Carvalho Guido, Miguel Prudêncio, Maisa da S. Araujo, Arlene G. Corrêa, Gustavo C. Cassiano, Anna C. C. Aguiar
Institutions: Universidade Federal de São Paulo, Universidade Federal de São Carlos, Fundação Oswaldo Cruz, Gulbenkian Institute for Molecular Medicine, Universidade Estadual de Campinas (UNICAMP), Universidade Nova de Lisboa, Universidade de São Paulo, Instituto de Física de São Carlos, University of Lisbon
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,935
Funders: Bill and Melinda Gates Foundation, “la Caixa” Foundation, Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Universidade de Lisboa, Universidade Nova de Lisboa, Universidade Estadual de Campinas, Ministério da Saúde, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa
Awards: Integrated investigation of inhibitors active on infectious diseases: insights into molecular and cellular mechanisms of function, G1793764451, FIOCRUZ - to develop innovative tools that will help diagnose malaria cases, control malaria transmission and improve effectiveness of malaria treatment in t..., Sustainable synthetic methods employing catalysis, benign solvents, safer reagents, and bio-renewable feedstock, G192812035, CIBFar - Center for Innovation in Biodiversity and Drug Discovery, G22113365, G2510811000, G2549540120, G2634235941, G266594711, G295657101, Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax, G3327196688, G3690646728, G3995495987, G407438531, G4110902315, Identification of new antimalarial compounds: a multidisciplinary strategy aimed to search for potent chemical classes against new molecular targets and different stages of life of Plasmodium spp, G4648375610, G4679785004, G5754763454, G5960408532, G6438247056, G6779583974, G6822879463, G6879302011, G7328220624, G7673248907, G801404012, G8120035943, G8573059934, G8670990856
OpenAlex ID: W4415935596