title: Synthesis, antiprotozoal and cytotoxic activities of new N-(3,4-dimethyl-5-isoxazolyl)-1,2-naphthoquinone-4-amino derivatives.
abstract: Three derivatives of N-(3,4-dimethyl-5-isoxazolyl)-1,2-naphthoquinone-4-amino (1), a compound which exhibits significant activity against Trypanosoma cruzi and Plasmodium falciparum but with cytotoxicity toward murine L-6 cells, were synthesized with the aim of ameliorating its cytotoxicity. The in vitro antiprotozoal and cytotoxic activities of the synthesized compounds were evaluated against T. cruzi, Trypanosoma brucei rhodesiense, P. falciparum and murine L-6 cells. The hydroxymethyl (2) and the oxime (3) derivatives were active against T. cruzi, with IC50 values in a range comparable to those of 1 (IC50: 0.65 microg/ml) and benznidazole (IC50: 0.56 microg/ml) while the carboxymethyloxime (4) was inactive. Compounds 2 and 3 were cytotoxic toward L-6 cells, with IC50 values identical to that of 1 (IC50: 0.50 microg/ml). The results did not support the suggestion that 2 and 3 may be used as prodrugs of 1.
authors.affiliation: Dpto. de Farmacia, Faculdad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina. nrscor@dqo.fcq.unc.edu.ar
authors.forename: N R
authors.initials: NR
authors.lastname: Sperandeo
authors.forename: M C
authors.initials: MC
authors.lastname: Briñón
authors.forename: R
authors.initials: R
authors.lastname: Brun
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000639:trends; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats; D013557:Switzerland; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents; D007555:Isoxazoles; D009285:Naphthoquinones; C066271:N-(3,4-dimethyl-5-isoxazolyl)-4-amino-1,2-naphthoquinone