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J Inorg Biochem ; 192: 107-118, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30640150

RESUMO

Four binuclear phosphanesilver(I) dithiocarbamates, {cyclohexyl3PAg(S2CNRR')}2 for R = R' = Et (1), CH2CH2 (2), CH2CH2OH (3) and R = Me, R' = CH2CH2OH (4) have been synthesised and characterised by spectroscopy and crystallography, and feature tri-connective, µ2-bridging dithiocarbamate ligands and distorted tetrahedral geometries based on PS3 donor sets. The compounds were evaluated for anti-bacterial activity against a total of 12 clinically important pathogens. Based on minimum inhibitory concentration (MIC) and cell viability tests (human embryonic kidney cells, HEK 293), 1-4 are specifically active against Gram-positive bacteria while demonstrating low toxicity; 3 and 4 are active against methicillin resistant S. aureus (MRSA). Across the series, 4 was most effective and was more active than the standard anti-biotic chloramphenicol. Time kill assays reveal 1-4 to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Compound 4 demonstrates rapid (within 2 h) bactericidal activity at 1 and 2 × MIC to reach a maximum decrease of 5.2 log10 CFU/mL against S. aureus (MRSA).


Assuntos
Antibacterianos , Complexos de Coordenação , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Prata , Tiocarbamatos , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Cloranfenicol/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Avaliação Pré-Clínica de Medicamentos , Prata/química , Prata/farmacologia , Tiocarbamatos/síntese química , Tiocarbamatos/química , Tiocarbamatos/farmacologia
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