RESUMO
The reaction of 2,2-dimethoxy-N-methylethyllamine or 2-methyl-1,3-dioxolane with CS(2) in alkaline media produced two novel dithiocarbamate salts. Subsequent reactions with organotin halides yielded six new complexes: [SnMe(2){S(2)CNR(R(1))(2)}(2)] (1), [Sn(n-Bu)(2){S(2)CNR(R(1))(2)}(2)] (2), [SnPh(2){S(2)CNR(R(1))(2)}(2)] (3), [SnMe(2){S(2)CNR(R(2))(2)}(2)] (4), [Sn(n-Bu)(2){S(2)CNR(R(2))(2)}(2)] (5), [SnPh(2){S(2)CNR(R(2))(2)}(2)] (6), where R = methyl, R(1) = CH(2)CH(OMe)(2), and R(2) = 2-methyl-1,3-dioxolane. All compounds were identified in terms of infrared, (1)H and (13)C NMR, and the complexes were also characterized using (119)Sn NMR, (119)Sn Mössbauer and X-ray crystallography. The biological activity of all derivatives has been screened in terms of IC(90) and IC(50) against Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, Penicillium citrinum, Curvularia senegalensis, Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Streptococcus sanguinis, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, and Pseudomonas aeruginosa and the results correlated well with a performed study of structure-activity relationship (SAR). Complexes (3), (5) and (6) displayed the best IC(90) and IC(50) in the presence of the fungi, greater than that of miconazole, used as control drug.
Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Desenho de Fármacos , Fungos/efeitos dos fármacos , Compostos Orgânicos de Estanho/farmacologia , Tiocarbamatos/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Bactérias/crescimento & desenvolvimento , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Fungos/crescimento & desenvolvimento , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/química , Relação Estrutura-Atividade , Tiocarbamatos/síntese química , Tiocarbamatos/químicaRESUMO
The reaction of 1,3-cyclohexadione with 2-aminobenzoic acid has produced the 2-(3-oxocyclohex-1-enyl)benzoic acid (HOBz). Subsequent reactions of the ligand with organotin chlorides led to [Me(2)Sn(OBz)O](2) (1), [Bu(2)Sn(OBz)O](2) (2), [Ph(2)Sn(OBz)O](2) (3), [Me(3)Sn(OBz)] (4), [Bu(3)Sn(OBz)] (5) and [Ph(3)Sn(OBz)] (6). All complexes have been fully characterized. In addition the structure of complexes (2) and (4) have been authenticated by X-ray crystallography. The biological activity of all derivatives has been screened against Cryptococcus neoformans and Candida albicans. In addition we have performed toxicological testes employing human kidney cell. The complexes (3), (5) and (6) displayed the best values of inhibition of the fungus growing, superior to ketoconazole. Compound (5) presented promising results in view of the antifungal and cytotoxicity assays.
Assuntos
Ácido Benzoico/química , Candida albicans/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Ácidos Cicloexanocarboxílicos/química , Desinfetantes/síntese química , Desinfetantes/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Linhagem Celular , Cristalografia por Raios X , Desinfetantes/química , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Estrutura Molecular , Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologiaRESUMO
Structural studies and an investigation of the cytotoxic activity of Sn(IV) complexes with N(4)-phenyl-2-benzoylpyridine thiosemicarbazone (H2Bz4Ph) were carried out. The crystal and molecular structures of [Sn(2Bz4Ph)Cl3].CH3CH2OH (1) and [Sn(2Bz4Ph)BuCl2].H2O (Bu = butyl group) (2) were determined. Both compounds present octahedral coordination geometry with the 2Bz4Ph anionic ligand behaving as tridentate on the metal ion. A comparative study of the structures of these compounds along with that of [Sn(2Bz4Ph)Bu2Cl] (3) determined before is presented. The cytotoxicity of H2Bz4Ph and its Sn(IV) complexes was investigated against the MCF-7, TK-10 and UACC-62 human tumor cell lines. Among the three complexes, 3 proved to be better as cytotoxic agent than the clinically used drug etoposide. H2Bz4Ph and all complexes were able to induce apoptosis in UACC-62 cells.