The Marine Microbial Alkaloid (R)-Salsolinol is Effective Against Trypanosoma cruzi

Author(s)

Abiuzi, Mariana B. ; de Andrade, Beatriz A. ; Ramos, Fernanda F. ; Totini, Carlos H. ; Christodoulides, Myron ; Kant, Ravi ; Lago, Joao Henrique G. ; Tempone, Andre G.

• Document type: Journal article
• Source: CHEMISTRY & BIODIVERSITY; v. N/A, p. 9-pg., 2025-03-15.

Abstract

Chagas disease is a parasitic disease with approximately 8 million people infected worldwide, presenting a limited and toxic treatment. Comprising a vast chemodiversity, microbial metabolites are among the most important sources of FDA-approved anti-infectives. In this work, the bioactivity-guided fractionation from an extract obtained from the bacterium Bacillus altitudinis, isolated from a red seaweed, afforded an antitrypanosomal alkaloid which was characterized as (R)-salsolinol by H-1 NMR and HR-ESIMS analysis. (R)-Salsolinol showed a trypanocidal effect against the trypomastigotes (EC50 = 14 mu g/mL) and a selective activity against the intracellular amastigotes (EC50 = 19 mu g/mL), with no mammalian cytotoxicity in human monocytic cells THP-1 (CC50 > 36 mu g/mL). In silico studies predicted a high permeability into cell membranes, as well as a high gastrointestinal absorption, with acceptable parameters in pharmaceutical filters, as well as cruzipain as a possible target protein, suggesting that (R)-salsolinol can be used as a prototype for drug design studies in Chagas disease. (AU)

• FAPESP's process: 23/12447-1 - Searching for specialized metabolites from Brazilian floristic biodiversity as drug candidates for neglected tropical diseases
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
• FAPESP's process: 24/19277-7 - Silver nanoparticles obtained from natural products for the treatment of infections caused by multiresistant bacteria
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: Regular Research Grants
• FAPESP's process: 23/07414-7 - Isolation and Antitrypanosomal Evaluation of Secondary Metabolites from the Marine Bacteria Bacillus altitudinis
• Grantee: Mariana Babberg Abiuzi
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 21/04464-8 - Microbial and plant prototypes as drug candidates for protozoan neglected diseases and multidrug-resistant bacteria
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants