Effective Tetradentate Compound Complexes against Leishmania spp. that Act on Critical Enzymatic Pathways of These Parasites 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, Clotilde Amastigote Antileishmania Antiproliferative Leishmania spp. Promastigote SOD Tetradentate polyaminic compounds Ultrastructure 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. 2019-04-08T12:36:19Z 2019-04-08T12:36:19Z 2018-12-31 info:eu-repo/semantics/article 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. 1420-3049 http://hdl.handle.net/10481/55392 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI