In vitro activity and biochemical effectiveness of new organometallic complexes of osmium(III) against Leishmania donovani and Trypanosoma cruzi.
In the present paper, the in vitro activities of 10 osmium(III) complexes with [OSIII(L)] degrees structure against promastigote forms of Leishmania donovani and epimastigote forms of Trypanosoma cruzi haven been assayed. The complexes OSIII-2,4dinitroimidazole dithiocarbamate, OSIII-4-nitroimidazole dithiocarbamate, OSIII-benznidazole dithiocarbamate and OSIII-2-amino-6-Br-benzothiazole dithiocarbamate induced high percentages of growth inhibition in the parasites. The four compounds showed moderate cell toxicity. The inhibitory effects of these complexes on macromolecule synthesis have been evaluated using [3H]-thymidine, [3H]-uridine and [3H]-leucine incorporation. These metal-drug complexes clearly inhibit the DNA, RNA and protein synthesis, as well as the enzymatic activities of succinate dehydrogenase, malate dehydrogenase and pyruvate kinase.
Castilla
J J
JJ
Grupo de Investigación en Bioquímica y Parasitologia Molecular, Facultad de Ciencias, Universidad de Granada, Spain.
Mesa-Valle
C M
CM
Sanchez-Moreno
M
M
Arnedo
T
T
Rosales
M J
MJ
Mascaro
C
C
Craciunescu
D
D
Osuna
A
A
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D016054:DNA, Protozoan / Q000096:biosynthesis; D005260:Female; D007893:Leishmania donovani / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D009682:Magnetic Resonance Spectroscopy; D008291:Malate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000494:pharmacology*; D017892:Osmium Compounds / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000096:biosynthesis; D011770:Pyruvate Kinase / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism; D014709:Vero Cells
D000981:Antiprotozoal Agents; D016054:DNA, Protozoan; D009942:Organometallic Compounds; D017892:Osmium Compounds; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D012313:RNA; D008291:Malate Dehydrogenase; D013385:Succinate Dehydrogenase; D011770:Pyruvate Kinase