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1.
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
2.
Eur J Med Chem ; 42(2): 205-13, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17189664

RESUMO

2,6-Bis(benzimidazol-2-yl)pyridine (L) ligand and complexes [M(L)Cl(2)] and [Fe(L)(2)](ClO(4))(2) (M=Zn, Cd, Hg) have been synthesized. The geometries of the [M(L)Cl(2)] complexes were derived from theoretical calculation in DGauss/DFT level (DZVP basis set) on CACHE. The central M(II) ion is penta-coordinated and surrounded by N(3)Cl(2) environment, adopting a distorted trigonal bipyramidal geometry. The ligand is tridentate, via three nitrogen atoms to metal centre and two chloride ions lie on each side of the distorted benzimidazole ring. In the [Fe(L)(2)](ClO(4))(2) complex, the central Fe(II) ion is surrounded by two (3N) units, adopting a octahedral geometry. The elemental analysis, molecular conductivity, FT-Raman, FT-IR (mid-, far-IR), (1)H, and (13)C NMR were reported. The antimicrobial activities of the free ligand, its hydrochloride salt, and the complexes were evaluated using the disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against 10 bacteria and the results compared with that for gentamycin. Antifungal activities were reported for Candida albicans, Kluyveromyces fragilis, Rhodotorula rubra, Debaryomyces hansenii, Hanseniaspora guilliermondii, and the results were referenced against nystatin, ketaconazole, and clotrimazole antifungal agents. In most cases, the compounds tested showed broad-spectrum (Gram positive and Gram negative bacteria) activities that were either more effective than or as potent as the references. The binding of two most biologically effective compounds of zinc and mercury to calf thymus DNA has also been investigated by absorption spectra.


Assuntos
Antibacterianos/síntese química , Antifúngicos/síntese química , Quelantes/síntese química , Metais Pesados , Compostos Organometálicos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Cádmio , Quelantes/química , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Compostos Ferrosos/síntese química , Compostos Ferrosos/química , Compostos Ferrosos/farmacologia , Ligantes , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Compostos Organomercúricos/síntese química , Compostos Organomercúricos/química , Compostos Organomercúricos/farmacologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Relação Estrutura-Atividade , Zinco
3.
Eur J Ophthalmol ; 17(3): 368-71, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17534818

RESUMO

PURPOSE: To determine the intraocular penetration of topical drops of betaxolol HCl 0.25% suspension and betaxolol HCl 0.50% solution into the aqueous humor. METHODS: Fifteen patients were randomly assigned to receive topical betaxolol HCl 0.25% suspension (n=7) or topical betaxolol HCl 0.50% solution (n=8) the day before cataract surgery. Aqueous samples were collected 2 hours after the administration of the morning dose during cataract surgery. Drug concentrations were determined by high-performance liquid chromatography with fluorescence detection. RESULTS: The mean aqueous humor concentration of topical betaxolol HCl 0.25% suspension was 275.1+/-168.8 micro g/mL (range 570-70 micro g/mL) and the mean aqueous humor concentration of topical betaxolol HCl 0.50% solution was 195.4+/-102.4 micro g/mL (range 334-50 micro g/mL) (p=0.281). CONCLUSIONS: The mean aqueous humor concentration of betaxolol 0.25% suspension was higher than betaxolol 0.50% solution; however, the difference was not statistically significant. With twofold reduced concentration and similar anterior chamber penetration, betaxolol 0.25% suspension could be first choice for Beta 1 selective blocker therapy when considered for patients with glaucoma.


Assuntos
Antagonistas Adrenérgicos beta/farmacocinética , Humor Aquoso/metabolismo , Betaxolol/farmacocinética , Adolescente , Adulto , Idoso , Extração de Catarata , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/farmacocinética , Estudos Prospectivos , Suspensões/farmacocinética
5.
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
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