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Volume 16
Issue 5
10.3390/metabo16050322
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Targeting Leishmania Fe-SOD and Glucose Metabolism with Tripodal and Pyridinacyclophane Polyamines as a Chemotherapeutic Strategy

by
Álvaro Martín-Montes
1,2,
Estefanía Delgado-Pinar
3,
Irene Bonastre
3,
M. Paz Clares
4,
Begoña Verdejo
3,
Álvaro Martínez-Camarena
5,
Rafael Ballesteros-Garrido
4,
Rubén Martín-Escolano
6,7,
Mª José Rosales-Lombardo
1,
Enrique García-España
3 and
Clotilde Marín
1,*
1
Departamento de Parasitología, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain
2
Facultad de Salud y Deporte, Universidad Alfonso X el Sabio-Mare Nostrum, Camino de la Térmica, 90, 29004 Málaga, Spain
3
Departamento de Química Inorgánica, Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático José Beltrán 2, 46980 Paterna (Valencia), Spain
4
Departament de Química Física, Universitat de València, Av. Vicent Andrés Estellés, 22, 46100 Burjassot (València), Spain
5
Departament de Química Orgànica, Universitat de València, Av. Vicent Andrés Estellés, 19, 46100 Burjassot (Valencia), Spain
6
Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain
7
Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Metabolites 2026, 16(5), 322; https://doi.org/10.3390/metabo16050322
Submission received: 20 March 2026 / Revised: 30 April 2026 / Accepted: 1 May 2026 / Published: 12 May 2026
(This article belongs to the Special Issue Metabolomics in Infectious Diseases)
Versions Notes

Abstract

Background/Objectives: Many parasitic diseases remain without an effective treatment and cause many deaths worldwide. Leishmaniasis is a complex disease that belongs to the category of Neglected Tropical Diseases, as its treatment relies on outdated drugs that also lead to resistance and negative side-effects. To address this problem, two new chemical families have been tested in vitro against three of the most common parasites from the genus Leishmania. Methods: One family is formed by the polyamine tris(2-aminoethyl)amine functionalised either in one or its three primary amines with different aryl group, and the other is a group of azamacrocyclic cyclophanes containing either one or two aromatic spacers. Results: From the first family, only one compound showed activity against Leishmania donovani, and from the second family, three compounds were selective, two of them for Leishmania braziliensis and a different one against L. donovani, another parasite of the studied genus. Conclusions: The anti-Leishmania activity seems to be related to the compounds’ ability to inhibit the iron superoxide dismutase activity and to alter the parasite metabolism by inhibiting glucose intake in L. braziliensis or by accelerating it in L. donovani and by attacking the parasite defences against ROS, both effects triggering a mitochondrial membrane depolarization that enhances damage, leading to cell death.
Keywords: Leishmania; glucose metabolism; polyamine; superoxide dismutase Leishmania; glucose metabolism; polyamine; superoxide dismutase

Share and Cite

MDPI and ACS Style

Martín-Montes, Á.; Delgado-Pinar, E.; Bonastre, I.; Clares, M.P.; Verdejo, B.; Martínez-Camarena, Á.; Ballesteros-Garrido, R.; Martín-Escolano, R.; Rosales-Lombardo, M.J.; García-España, E.; et al. Targeting Leishmania Fe-SOD and Glucose Metabolism with Tripodal and Pyridinacyclophane Polyamines as a Chemotherapeutic Strategy. Metabolites 2026, 16, 322. https://doi.org/10.3390/metabo16050322

AMA Style

Martín-Montes Á, Delgado-Pinar E, Bonastre I, Clares MP, Verdejo B, Martínez-Camarena Á, Ballesteros-Garrido R, Martín-Escolano R, Rosales-Lombardo MJ, García-España E, et al. Targeting Leishmania Fe-SOD and Glucose Metabolism with Tripodal and Pyridinacyclophane Polyamines as a Chemotherapeutic Strategy. Metabolites. 2026; 16(5):322. https://doi.org/10.3390/metabo16050322

Chicago/Turabian Style

Martín-Montes, Álvaro, Estefanía Delgado-Pinar, Irene Bonastre, M. Paz Clares, Begoña Verdejo, Álvaro Martínez-Camarena, Rafael Ballesteros-Garrido, Rubén Martín-Escolano, Mª José Rosales-Lombardo, Enrique García-España, and et al. 2026. "Targeting Leishmania Fe-SOD and Glucose Metabolism with Tripodal and Pyridinacyclophane Polyamines as a Chemotherapeutic Strategy" Metabolites 16, no. 5: 322. https://doi.org/10.3390/metabo16050322

APA Style

Martín-Montes, Á., Delgado-Pinar, E., Bonastre, I., Clares, M. P., Verdejo, B., Martínez-Camarena, Á., Ballesteros-Garrido, R., Martín-Escolano, R., Rosales-Lombardo, M. J., García-España, E., & Marín, C. (2026). Targeting Leishmania Fe-SOD and Glucose Metabolism with Tripodal and Pyridinacyclophane Polyamines as a Chemotherapeutic Strategy. Metabolites, 16(5), 322. https://doi.org/10.3390/metabo16050322

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