Marine Guanidine Alkaloids Inhibit Malaria Parasites Development in <i>In Vitro</i>, <i>In Vivo</i> and <i>Ex Vivo</i> Assays
Malaria is a disease caused by pathogenic protozoa <i>Plasmodium</i> spp., with a significant global impact on human health. Increasing resistance of <i>P. falciparum</i> strains to drugs treating malaria highlights the urgent need for the discovery of new antimalarial candidates. Batzelladines are marine guanidine alkaloids that exhibit potent antiparasitic activity. Herein, results of the parasitological profiling assessment of batzelladines F and L are reported. Both compounds exhibited potent antiplasmodial activity, moderate cytotoxicity, and suitable selectivity indexes. Batzelladines F and L are fast-acting <i>P. falciparum</i> inhibitors, with a pronounced inhibitory activity against resistant strains and laboratory-adapted clinical isolates of <i>P. falciparum</i>. Batzelladines F and L also demonstrated <i>ex vivo</i> activity against clinical isolates of <i>P. falciparum</i> and <i>P. vivax</i>, and batzelladine F showed <i>in vivo</i> antimalarial activity in a <i>P. berghei</i> malaria model. The results reported constitute a robust rationale for the development of guanidine alkaloid derivatives as lead candidates for malaria treatment.
Authors
- Igor M. R. Moura (ORCID: https://orcid.org/0000-0003-3279-6894)
- Antônio G. Ferreira (ORCID: https://orcid.org/0000-0003-2314-216X)
- Guilherme de Souza (ORCID: https://orcid.org/0000-0003-3278-6688)
- Vinícius Bonatto (ORCID: https://orcid.org/0000-0002-3119-0447)
- Dhélio B. Pereira (ORCID: https://orcid.org/0000-0002-7761-5498)
- Carolina Bioni Garcia Teles (ORCID: https://orcid.org/0000-0002-4529-2137)
- Roberto G. S. Berlinck (ORCID: https://orcid.org/0000-0003-0118-2523)
- Eduardo Hajdu (ORCID: https://orcid.org/0000-0002-8760-9403)
- Sarah El Chamy Maluf (ORCID: https://orcid.org/0000-0002-3050-7473)
- Anna Caroline Campos Aguiar (ORCID: https://orcid.org/0000-0003-0139-8279)
- Marcelo R. de Amorim (ORCID: https://orcid.org/0000-0002-7113-911X)
- Amália dos Santos Ferreira
- Rafael V. C. Guido (ORCID: https://orcid.org/0000-0002-7187-0818)
- Camila de Souza Barbosa (ORCID: https://orcid.org/0000-0001-9631-3172)
- Natália M. Moreira (ORCID: https://orcid.org/0000-0001-7996-2859)
- Giovana Rossi Mendes
- Fabio Cardoso Cruz (ORCID: https://orcid.org/0000-0003-3765-7148)
- Almério Noronha
Institutions
- Universidade Federal do Rio de Janeiro (BR)
- Universidade Federal de São Carlos (BR)
- Universidade de São Paulo (BR)
- Faculdades Oswaldo Cruz (BR)
- National Archaeology Museum (PT)
- FZU ‒ Institute of Physics of the Academy of Sciences of the Czech Republic (CZ)
- Instituto de Psicologia Comportamental de São Carlos (BR)
- Fundação Oswaldo Cruz (BR)
- Universidade Federal de São Paulo (BR)
Publication Details
- Journal
- ACS Infectious Diseases
- Published
- 2025-04-15
- DOI
- https://doi.org/10.1021/acsinfecdis.4c00714
- Citations
- 7
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 13.15
Funders
- 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