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1.
Eur J Med Chem ; 44(11): 4681-9, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19700225

RESUMO

Series of new mixed aza-oxo-thia macrocyclic ligands 1,9(2,6)-ditriazina-2,8,10,16-tetraaza-3,7,11,15-tetraoxo-5,13-dithia-cyclohexadecaphan-1(4),9(4)-diphenyl (L(1)); 1,10(2,6)-ditri azina-2,9,11,18-tetraaza-3,8,12,17-tetraoxo-5,6,14,15-tetrathia-cyclooctadecaphan-1(4),10(4)-diphenyl (L(2)); 1,11(2,6)-ditriazina-2,10,12,20-tetraaza-3,9,13,19-tetraoxo-6,16-dithia-cyclocosa-phan-1(4),11(4)-diphenyl (L(3)); 1,12(2,6)-ditriazina-2,11,13,22-tetraaza-3,10,14,21-tetraoxo-6,7,17,18-tetrathia-cyclodocosaphan-1(4),12(4)-diphenyl (L(4)) were synthesised. The structural features of the compounds have been studied by elemental analyses, Mass, FT-Raman, FT-IR, (1)H and (13)C NMR spectroscopy. The antimicrobial activities of the ligands were evaluated using disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against several bacteria and yeast cultures. The obtained results from both methods were assessed in side-by-side comparison with commercial antibacterial and antifungal agents. In most cases, the compounds show strong antifungal activity in the comparison tests. Cytotoxic activities of the ligands against two different human cancer cell lines, stomach (23132/87) and lung (A549) were determined by MTT assay. DNA fragmentation assay tested cell lines were used to analyze the DNA ladder formation which is a characteristic of apoptotic cell death. The binding of the ligands with calf thymus DNA (CT-DNA) has also been investigated by absorption spectroscopy.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Apoptose/efeitos dos fármacos , DNA/metabolismo , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Bovinos , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Leveduras/efeitos dos fármacos
2.
Eur J Med Chem ; 42(8): 1069-75, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17350734

RESUMO

The 1,6-bis(benzimidazol-2-yl)-3,4-dithiahexane (1) ligand and its palladium(II) chloride complex [(micro(2)-SCH(2)CH(2)NHNCC(6)H(4))PdCl](2)xC(2)H(5)OH (2) have been synthesised and characterised by spectroscopical methods. The crystal structure of the triclinic title compound (P-1 (no. 2), a=879.6(1) pm, b=984.4(1) pm, c=1471.8(2) pm; alpha=94.330(6) degrees , beta=98.546(6) degrees , gamma=99.258(7) degrees , Z=2) was solved from X-ray single crystal diffraction data. In the binuclear complex, each palladium atom is coordinated in a slightly distorted square-planar arrangement by one nitrogen, two bridging sulphurs and one terminal chlorine atom. Molar conductivity, FT-Raman, FT-IR (mid-i.r., far-i.r.), (1)H and (13)C NMR spectra of the complex (2) have been recorded and show a good accordance with the square-planar geometry. The antimicrobial and antifungal activities of palladium(II) chloride, free ligand, its hydrochloride salt and the complex were evaluated using the disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) the dilution method, against 10 bacteria and five yeast cultures. The results for the antibacterial from the disk diffusion method were assessed in side-by-side comparison with those for penicillin-g, ampicillin, cefotaxime, vancomycin, ofloxacin and tetracycline. Antifungal activities were referenced with nystatin, ketaconazole, and clotrimazole, commercial antifungal agents. The data from the dilution procedure were compared with gentamycin as antibacterial and nystatin as antifungal agent, respectively. In most cases, the compounds tested showed broad-spectrum (Gram positive and Gram negative) activities that were comparatively more active, or as potent as referenced pharmaceutical agents. The palladium complex has the potential to generate new kind of metabolites by displaying high affinities for most of the receptors compared with palladium chloride, free ligand and its hydrochloride salt.


Assuntos
Anti-Infecciosos/química , Compostos Organometálicos/farmacologia , Paládio/farmacologia , Análise Espectral , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Organometálicos/uso terapêutico , Paládio/uso terapêutico , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Leveduras/efeitos dos fármacos
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