Identification of Aryl Polyamines Derivatives as Anti- Trypanosoma cruzi Agents Targeting Iron Superoxide Dismutase †

Martín-Escolano, Rubén, Molina-Carreño, Daniel, Martín-Escolano, Javier, Clares, Mª Paz, Galiana-Roselló, Cristina, González-García, Jorge, Cirauqui, Nuria, Llinares, José M., Rosales, María José, García-España, Enrique, and others. (2022) Identification of Aryl Polyamines Derivatives as Anti- Trypanosoma cruzi Agents Targeting Iron Superoxide Dismutase †. Pharmaceutics, 15 (1). Article Number 140. ISSN 1999-4923. (doi:10.3390/pharmaceutics15010140) (KAR id:99386)

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Official URL: https://doi.org/10.3390/pharmaceutics15010140

Abstract

Chagas disease (CD) is a tropical and potentially fatal infection caused by Trypanosoma cruzi. Although CD was limited to Latin America as a silent disease, CD has become widespread as a result of globalization. Currently, 6–8 million people are infected worldwide, and no effective treatment is available. Here, we identify new effective agents against T. cruzi. In short, 16 aryl polyamines were screened in vitro against different T. cruzi strains, and lead compounds were evaluated in vivo after oral administration in both the acute and chronic infections. The mode of action was also evaluated at the energetic level, and its high activity profile could be ascribed to a mitochondria-dependent bioenergetic collapse and redox stress by inhibition of the Fe-SOD enzyme. We present compound 15 as a potential compound that provides a step forward for the development of new agents to combat CD.

Item Type:	Article
DOI/Identification number:	10.3390/pharmaceutics15010140
Uncontrolled keywords:	chagas disease, chemotherapy, drug discovery, aryl polyamines, Trypanosoma cruzi
Subjects:	Q Science > QH Natural history > QH301 Biology
Divisions:	Divisions > Division of Natural Sciences > Biosciences
Funders:	Ministry of Economy, Industry and Competitiveness (https://ror.org/034900433) Federación Española de Enfermedades Raras (https://ror.org/0348bpk17)
SWORD Depositor:	JISC Publications Router
Depositing User:	JISC Publications Router
Date Deposited:	18 Jan 2023 14:22 UTC
Last Modified:	22 Feb 2023 15:49 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/99386 (The current URI for this page, for reference purposes)
Martín-Escolano, Rubén:	https://orcid.org/0000-0002-6262-9344
Galiana-Roselló, Cristina:	https://orcid.org/0000-0003-1365-1323
González-García, Jorge:	https://orcid.org/0000-0001-8994-1779
Marín, Clotilde:	https://orcid.org/0000-0002-4316-2742

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