Marine Guanidine Alkaloids Inhibit Malaria Parasites Development in In Vitro, In Vivo and Ex Vivo Assays

  • ACS Infect Dis. 2025 Apr 15. doi: 10.1021/acsinfecdis.4c00714.
Giovana Rossi Mendes  1 ,  Anderson L Noronha  2 ,  Igor M R Moura  1 ,  Natália Menezes Moreira  1 ,  Vinícius Bonatto  1 ,  Camila S Barbosa  1 ,  Sarah El Chamy Maluf  1 ,  Guilherme Eduardo de Souza  1 ,  Marcelo Rodrigues de Amorim  2 ,  Anna Caroline Campos Aguiar  1  3 ,  Fabio C Cruz  4 ,  Amália Dos Santos Ferreira  5 ,  Carolina B G Teles  5 ,  Dhelio B Pereira  6 ,  Eduardo Hajdu  7 ,  Antonio G Ferreira  8 ,  Roberto G S Berlinck  2 ,  Rafael Victorio Carvalho Guido  1
Affiliations
  • 1. São Carlos Institute of Physics, University of Sao Paulo, CEP 13563-120 São Carlos, SP, Brazil.
  • 2. Instituto de Química de São Carlos, Universidade de São Paulo, CEP 13560-970 São Carlos, SP, Brazil.
  • 3. Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, CEP 04023-062 São Paulo, SP, Brazil.
  • 4. Department of Pharmacology, Federal University of São Paulo, CEP 04023-062 São Paulo, SP, Brazil.
  • 5. Oswaldo Cruz Foundation, Leishmaniasis and Malaria Bioassay Platform, CEP 76812-245 Porto Velho, Rondônia, Brazil.
  • 6. Research Center in Tropical Medicine of Rondônia, CEP 76812-329 Porto Velho, RO, Brazil.
  • 7. Museu Nacional, Universidade Federal do Rio de Janeiro, CEP 20940-040 Rio de Janeiro, RJ, Brazil.
  • 8. Departamento de Química, Universidade Federal de São Carlos, CEP 13565-905 São Carlos, SP, Brazil.
PMID: 40233359 DOI: 10.1021/acsinfecdis.4c00714
Abstract

Malaria is a disease caused by pathogenic protozoa Plasmodium spp., with a significant global impact on human health. Increasing resistance of P. falciparum 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 P. falciparum inhibitors, with a pronounced inhibitory activity against resistant strains and laboratory-adapted clinical isolates of P. falciparum. Batzelladines F and L also demonstrated ex vivo activity against clinical isolates of P. falciparum and P. vivax, and batzelladine F showed in vivo antimalarial activity in a P. berghei malaria model. The results reported constitute a robust rationale for the development of guanidine alkaloid derivatives as lead candidates for malaria treatment.

Keywords
Plasmodium falciparum; guanidine alkaloids; malaria; marine natural products.
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