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Article

Effective Tetradentate Compound Complexes against Leishmania spp. that Act on Critical Enzymatic Pathways of These Parasites

1
Department of Parasitology, Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada/University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain
2
QBIS-CAT Research Group, Institut de Química Computacional i Catàlisi (IQCC), and Departament de Química, Universitat de Girona. Campus de Montilivi, E-17071 Girona, Spain
*
Authors to whom correspondence should be addressed.
Molecules 2019, 24(1), 134; https://doi.org/10.3390/molecules24010134
Received: 23 November 2018 / Revised: 18 December 2018 / Accepted: 21 December 2018 / Published: 31 December 2018
(This article belongs to the Section Medicinal Chemistry)
The spectrum and efficacy of available antileishmanial drugs is limited. In the present work we evaluated in vitro the antiproliferative activity of 11 compounds based on tetradentate polyamines compounds against three Leishmania species (L. braziliensis, L. donovani and L. infantum) and the possible mechanism of action. We identified six compounds (3, 5, 6, 7, 8 and 10) effective against all three Leishmania spp both on extracellular and intracellular forms. These six most active leishmanicidal compounds also prevent the infection of host cells. Nevertheless, only compound 7 is targeted against the Leishmania SOD. Meanwhile, on the glucose metabolism the tested compounds have a species-specific effect on Leishmania spp.: L. braziliensis was affected mainly by 10 and 8, L. donovani by 7, and L. infantum by 5 and 3. Finally, the cellular ultrastructure was mainly damaged by 11 in the three Leishmania spp. studied. These identified antileishmania candidates constitute a good alternative treatment and will be further studied. View Full-Text
Keywords: amastigote; antileishmania; antiproliferative; Leishmania spp.; promastigote; SOD; tetradentate polyaminic compounds; ultrastructure amastigote; antileishmania; antiproliferative; Leishmania spp.; promastigote; SOD; tetradentate polyaminic compounds; ultrastructure
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MDPI and ACS Style

Urbanová, K.; Ramírez-Macías, I.; Martín-Escolano, R.; Rosales, M.J.; Cussó, O.; Serrano, J.; Company, A.; Sánchez-Moreno, M.; Costas, M.; Ribas, X.; Marín, C. Effective Tetradentate Compound Complexes against Leishmania spp. that Act on Critical Enzymatic Pathways of These Parasites. Molecules 2019, 24, 134. https://doi.org/10.3390/molecules24010134

AMA Style

Urbanová K, Ramírez-Macías I, Martín-Escolano R, Rosales MJ, Cussó O, Serrano J, Company A, Sánchez-Moreno M, Costas M, Ribas X, Marín C. Effective Tetradentate Compound Complexes against Leishmania spp. that Act on Critical Enzymatic Pathways of These Parasites. Molecules. 2019; 24(1):134. https://doi.org/10.3390/molecules24010134

Chicago/Turabian Style

Urbanová, Kristína, Inmaculada Ramírez-Macías, Rubén Martín-Escolano, María J. Rosales, Olaf Cussó, Joan Serrano, Anna Company, Manuel Sánchez-Moreno, Miquel Costas, Xavi Ribas, and Clotilde Marín. 2019. "Effective Tetradentate Compound Complexes against Leishmania spp. that Act on Critical Enzymatic Pathways of These Parasites" Molecules 24, no. 1: 134. https://doi.org/10.3390/molecules24010134

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