Effective Tetradentate Compound Complexes against Leishmania spp. that Act on Critical Enzymatic Pathways of These Parasites
Metadatos
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Urbanová, Kristína; Ramírez Macías, Inmaculada; Martín-Escolano, Rubén; Rosales Lombardo, María José; Cussó, Olaf; Serrano, Joan; Llamas Company, Inmaculada; Sánchez Moreno, Manuel; Costas, Miquel; Ribas, Xavi; Marín Sánchez, ClotildeEditorial
MDPI
Materia
Amastigote Antileishmania Antiproliferative Leishmania spp. Promastigote SOD Tetradentate polyaminic compounds Ultrastructure
Fecha
2018-12-31Referencia bibliográfica
Urbanová, K. [et al.]. Effective Tetradentate Compound Complexes against Leishmania spp. that Act on Critical Enzymatic Pathways of These Parasites. Molecules 2019, 24, 134; doi:10.3390/molecules24010134.
Patrocinador
This research was funded by THE SPANISH MINISTRY OF ECONOMY AND COMPETITIVENESS (MINECO), CONSOLIDER-INGENIO 2010, grant number CDS2010-00065; THE EUROPEAN RESEARCH FOUNDATION, grant number ERC-2009-StG-239910; THE MICINN, grant number CTQ2009-08464; and INNPLANTA, grant number INP-2011-0059-PCT-420000-ACT1.Resumen
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.