RESUMO
Redox-modulating anticancer drugs allow the exploitation of altered redox biology observed in many cancer cells. We discovered dinuclear RhIII(Cp*) and IrIII(Cp*) complexes that have in vitro anticancer activity superior to cisplatin and the investigational drug IT-139, while being less toxic in haemolysis and in vivo zebrafish models. The mode of action appears to be related to DNA damage and ROS-mediated stress pathways.
Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Dano ao DNA/efeitos dos fármacos , Irídio/química , Espécies Reativas de Oxigênio/metabolismo , Ródio/química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Hemólise , Humanos , Ligantes , Camundongos , Oxirredução , Rutênio/química , Relação Estrutura-Atividade , Peixe-ZebraRESUMO
BACKGROUND: Povidone-iodine is used as a cost-effective broad-spectrum antiseptic in the prophylaxis and treatment of certain ocular infections. In this study, the stability, ophthalmic irritation potential and antibacterial efficacy of an extemporaneous povidone-iodine preparation was determined using established ex vivo and in vitro assays. METHODS: Extemporaneous iodine was prepared by simple dilution in normal saline. Preparation stability was evaluated by monitoring concentration and pH. Ocular safety was determined using the bovine cornea opacity and permeability assay. Efficacy was assessed by determining the minimum inhibitory and minimum bactericidal concentration of the preparation on Staphylococcus aureus and Pseudomonas aeruginosa. RESULTS: Diluted povidone-iodine maintained its stability over the 28-day evaluation. The formulation caused mild ocular irritation at the lowest prepared concentration (0.5 per cent w/v), with irritation noticeably increased at higher concentrations. The preparation showed minimum bactericidal and inhibitory concentrations of 0.078 and 0.3 per cent w/v on S. aureus and P. aeruginosa, respectively. CONCLUSIONS: This study confirms the stability and broad-spectrum antibacterial efficacy of povidone-iodine, while addressing the ocular irritation potential of this chemical.
Assuntos
Antibacterianos/farmacologia , Córnea/efeitos dos fármacos , Córnea/microbiologia , Soluções Oftálmicas/farmacologia , Povidona-Iodo/farmacologia , Animais , Bovinos , Estabilidade de Medicamentos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
Eight linear analogues of the lipopeptide battacin were evaluated for their antibacterial activity against the Gram-positive Staphylococcus aureus. Of this library, the enantiomeric lipopeptide analogue 9.4 exhibited nanomolar inhibitory activity (MIC=200nmol) against S. aureus. Furthermore, this lipopeptide was resilient toward degradation conditions when exposed to rat serum proteases for up to 8h.
