Effective Tetradentate Compound Complexes against Leishmania spp. that Act on Critical Enzymatic Pathways of These Parasites
Kristína Urbanová,
Inmaculada Ramírez-Macías,
Rubén Martín-Escolano,
María José Rosales,
Olaf Cussó,
Joan Serrano,
Anna Company,
Manuel Sánchez-Moreno,
Miquel Costas,
Xavi Ribas,
Clotilde Marín
Affiliations
Kristína Urbanová
Department of Parasitology, Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada/University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain
Inmaculada Ramírez-Macías
Department of Parasitology, Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada/University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain
Rubén Martín-Escolano
Department of Parasitology, Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada/University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain
María José Rosales
Department of Parasitology, Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada/University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain
Olaf Cussó
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
Joan Serrano
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
Anna Company
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
Manuel Sánchez-Moreno
Department of Parasitology, Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada/University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain
Miquel Costas
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
Xavi Ribas
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
Clotilde Marín
Department of Parasitology, Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada/University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain
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.
