ABSTRACT
Topaquinone (TPQ) is a cofactor present at the active site of copper amine oxidases, derived from a Tyr residue inserted in the polypeptide chain through a copper-dependent but otherwise largely unknown mechanism. A simple model system was developed that permits to obtain the overall transformation of 4-tert-butylphenol, chosen as a model for Tyr, into a TPQ-like, para-hydroxyquinonic structure in the presence of Cu(II)-imidazole mononuclear complexes.
Subject(s)
Amine Oxidase (Copper-Containing)/metabolism , Benzoquinones/chemical synthesis , Copper/chemistry , Dihydroxyphenylalanine/analogs & derivatives , Phenols/chemistry , Dihydroxyphenylalanine/chemistry , Hydrogen-Ion Concentration , Hydroxylation , Lysine/analogs & derivatives , Lysine/chemistry , Oxidation-Reduction , Quinones/chemistryABSTRACT
The [Au(N-MeIm)Cl3], [Au(2-MeBO)Cl3] and [Au(2,5-diMeBO)Cl3] complexes (where N-MeIm = N-methylimidazole, 2-MeBO = 2-methylbenzoxazole and 2,5-diMeBO = 2,5-dimethylbenzoxazole), had been previously prepared and characterized by the Author. These compounds, when tested in vitro against murine leukemia cell lines L1210, human ovarian carcinoma A2780 and their sublines L1210/CDDP and A2780/CDDP resistant to cisplatin, in comparison with cisplatin and carboplatin, showed an interesting cytotoxicity, extended to resistant sublines.
Subject(s)
Antineoplastic Agents/chemical synthesis , Gold/pharmacology , Organometallic Compounds/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Drug Screening Assays, Antitumor , Female , Humans , Mice , Organometallic Compounds/pharmacology , Tumor Cells, CulturedABSTRACT
The [Pt(pyr)(N-Etlm)Cl4] complex, where pyr = pyrimidine and N-Etlm = N-ethylimidazole, previously prepared and characterized, showed an interesting cytotoxicity in vitro on the human ovarian carcinoma (A2780) and on his subline resistant to cis-platinum (A2780/CDDP), in comparison with cis-platinum and carboplatinum.
Subject(s)
Organoplatinum Compounds/pharmacology , Animals , Carboplatin/pharmacology , Cisplatin/pharmacology , Drug Screening Assays, Antitumor , Female , Humans , Leukemia/drug therapy , Mice , Ovarian Neoplasms/drug therapy , Tumor Cells, CulturedABSTRACT
Platinum(IV) chloride complexes with heterocyclic ligands have been prepared and characterized by infrared and electronic spectra. The compounds are of general formula Pt(L)nCl4, where L = N-ethylimidazole, N-propylimidazole, isoxazole, 3,5-dimethylisoxazole, benzoxazole, 2-methylbenzoxazole, 2,5-dimethylbenzoxazole, ethylenediamine, n = 2, 4, and also Pt(enEt2)3Cl4 X 2H2O, where enEt2 = N,N-diethylethylenediamine. These complexes are hexacoordinate with cis or trans configuration. The antitumoral activity of some complexes in mice inoculated with leukemia L1210 is reported.
Subject(s)
Antineoplastic Agents/chemical synthesis , Ethylenediamines/chemical synthesis , Imidazoles/chemical synthesis , Isoxazoles/chemical synthesis , Organoplatinum Compounds/chemical synthesis , Oxazoles/chemical synthesis , Animals , Ethylenediamines/therapeutic use , Imidazoles/therapeutic use , Indicators and Reagents , Isoxazoles/therapeutic use , Leukemia L1210/drug therapy , Male , Mice , Organoplatinum Compounds/therapeutic use , Oxazoles/therapeutic use , Spectrophotometry , Structure-Activity RelationshipABSTRACT
Platinum(II) halide complexes with N-ethylimidazole (N-EtIm) and N-propylimidazole (N-PropIm) of the Pt(L)2X2 and Pt(L)4X2 types (X = Cl, Br, I) were prepared and characterized by far infrared spectra, electronic spectra, and conductivity measurements. The inhibitorial activity of some complexes on the Ca,Mg-dependent ATPase and the antitumor studies of the Pt(L)4Cl2 derivatives have been investigated. Pt complexes are not inhibitory active in comparison to the same Pd complexes (if c = 10(-4) M). The LD50 in physiological solution for [Pt(N-EtIm)4]Cl2 X 2H2O and [Pt(N-PropIm)4]Cl2 are higher enough with respect to the cis platinum.
