Evaluation of the Activity of 4-Quinolones against Multi-Life Stages of <i>Plasmodium</i> spp.
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 <i>Plasmodium falciparum</i>, 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 <b>2</b>-<b>6</b>, displayed significant activity against <i>Plasmodium</i> sexual stages in both <i>ex vivo</i> and <i>in vivo</i> assays and effectively prevented hepatic cell infections, with compound <b>1</b> 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.
Authors
- Miguel Prudêncio (ORCID: https://orcid.org/0000-0003-1746-6029)
- Ana Alves (ORCID: https://orcid.org/0000-0001-7919-4896)
- Pedro Cravo (ORCID: https://orcid.org/0000-0003-1675-4504)
- Najara Akira Costa dos Santos
- Arlene G. Corrêa (ORCID: https://orcid.org/0000-0003-4247-2228)
- Jansen Fernandes Medeiros (ORCID: https://orcid.org/0000-0003-4196-8985)
- Everton M. da Silva (ORCID: https://orcid.org/0000-0003-4346-1803)
- Alice Oliveira Andrade
- Luis Carlos Salazar Alvarez (ORCID: https://orcid.org/0000-0001-5340-1412)
- Dhélio B. Pereira (ORCID: https://orcid.org/0000-0002-7761-5498)
- Carolina Bioni Garcia Teles (ORCID: https://orcid.org/0000-0002-4529-2137)
- Jéssica E. Araújo (ORCID: https://orcid.org/0000-0001-6683-3003)
- Wallyson de J. da Costa
- Fábio Trindade Maranhão Costa (ORCID: https://orcid.org/0000-0001-9969-7300)
- Anna Caroline Campos Aguiar (ORCID: https://orcid.org/0000-0003-0139-8279)
- Yasmin Annunciato (ORCID: https://orcid.org/0000-0003-1855-5170)
- Marcos L. Gazarini (ORCID: https://orcid.org/0000-0002-3882-6831)
- Alessandra da Silva Bastos
- Gustavo Capatti Cassiano (ORCID: https://orcid.org/0000-0002-6971-5974)
- João Pinto (ORCID: https://orcid.org/0000-0001-8572-7708)
- Rafael V. C. Guido (ORCID: https://orcid.org/0000-0002-7187-0818)
- Leandro do Nascimento Martinez (ORCID: https://orcid.org/0000-0003-0887-4784)
- Camila de Souza Barbosa (ORCID: https://orcid.org/0000-0001-9631-3172)
- Sofia Santana (ORCID: https://orcid.org/0000-0002-7459-9971)
- Roberto R. Moraes Barros (ORCID: https://orcid.org/0000-0002-0155-8431)
- Marcela Lucas Magalhães (ORCID: https://orcid.org/0000-0002-9546-4208)
- Maísa da Silva Araújo (ORCID: https://orcid.org/0000-0003-3607-0433)
- Caio S. Moura
- Eyob A. Workneh (ORCID: https://orcid.org/0009-0007-1562-9644)
- Matheus Santana
- Erica P. M. L. Peres
- Guilherme Campolina
Institutions
- Universidade Federal de Rondônia (BR)
- University of Lisbon (PT)
- Universidade Federal de São Carlos (BR)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Institute of Physics (PL)
- Instituto de Medicina Tropical (PY)
- Hospital de Egas Moniz (PT)
- Centro Universitário da Cidade (BR)
- Faculdades Integradas Aparício Carvalho (BR)
- Universidade Federal do ABC (BR)
- Universidade Nova de Lisboa (PT)
- Universidade Federal de São Paulo (BR)
Publication Details
- Journal
- ACS Omega
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1021/acsomega.5c08663
- Citations
- 1
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 1.88