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

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Mendes, Giovana Rossi ; Noronha, Anderson L. ; Moura, Igor M. R. ; Moreira, Natalia Menezes ; Bonatto, Vinicius ; Barbosa, Camila S. ; Maluf, Sarah El Chamy ; de Souza, Guilherme Eduardo ; de Amorim, Marcelo Rodrigues ; Aguiar, Anna Caroline Campos ; Cruz, Fabio C. ; Ferreira, Amalia dos Santos ; Teles, Carolina B. G. ; Pereira, Dhelio B. ; Hajdu, Eduardo ; Ferreira, Antonio G. ; Berlinck, Roberto G. S. ; Guido, Rafael Victorio Carvalho

• Document type: Journal article
• Source: ACS INFECTIOUS DISEASES; v. N/A, p. 14-pg., 2025-04-15.

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. (AU)

• FAPESP's process: 23/09209-1 - Desing and development of Plasmodium falciparum PI4K and PKG dual inhibitors as lead candidates for Malaria
• Grantee: Vinícius Bonatto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 21/03977-1 - Discovery of inhibitors from Brazilian Savana plants as lead compound candidates for Malaria
• Grantee: Igor Mota Rodrigues de Moura
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 22/01063-5 - Characterization of the antiplasmodial activity of natural products isolated from fungal metabolites as lead candidates for Malaria
• Grantee: Giovana Rossi Mendes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 22/15947-2 - Lead Identification and Optimization of Plasmodium falciparum Inhibitors as Drug Candidates for Malaria
• Grantee: Sarah El Chamy Maluf
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/17721-9 - The role of Chemistry in holobiont adaptation
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 24/04805-8 - Integrated investigation of inhibitors active on infectious diseases: insights into molecular and cellular mechanisms of function
• Grantee: Rafael Victorio Carvalho Guido
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/01229-5 - Bioactive metabolites of bacterial flora microorganisms from non-filtering marine animals
• Grantee: Marcelo Rodrigues de Amorim
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/01017-0 - Multi-use instrument approved and awarded in the project 2013/50228-8, name of instrument: ultra-performance liquid chromatograph coupled with a high resolution mass spectrometer
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 22/01066-4 - Discovery of natural products isolated from fungal lineages as lead candidates for Malaria
• Grantee: Natália Menezes Moreira Borges
• Support Opportunities: Scholarships in Brazil - Post-Doctoral