Adducts of nitroimidazole derivatives with rhodium(II) carboxylates: syntheses, characterization, and evaluation of antichagasic activities.
Adducts of several rhodium(II) carboxylates with two antiparasitic nitroimidazole ligands were prepared and characterized by elemental microanalysis, thermogravimetry, spectrophotometry (IR, UV, and visible), and proton magnetic resonance. Results of elemental and thermogravimetric analyses were consistent with the general formula Rh2(RCOO)4. 2L (R = aliphatic or aromatic carboxylic groups; L = metronidazole or benznidazole). The reddish-brown color of the adducts as well as their visible spectra suggest axial coordination of the nitroimidazole ligands through nitrogen atoms. NMR spectra indicate N3 as the coordinating atoms. Screening tests performed on cultures of T. cruzi indicate that aliphatic complexes--particularly propionate and acetate adducts--were more active than their aromatic counterparts, the same being observed with benznidazole adducts in relation to their metronidazole analogues. Evaluated for their usefulness as transfusion prophylactic agents against Chagas' disease, propionate derivatives failed to sterilize T. cruzi infected blood. An oral toxicity assay in mice showed mild toxic effects with daily doses of 5 mg/kg for 20 days.
Nothenberg
M S
MS
Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil.
Takeda
G K
GK
Najjar
R
R
D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D009593:Nitroimidazoles / Q000737:chemistry* / Q000494:pharmacology; D012238:Rhodium / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D002264:Carboxylic Acids; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D012238:Rhodium