RESUMO
Chemical control of mitochondrial dynamics and bioenergetics can unravel fundamental biological mechanisms and therapeutics for several diseases including, diabetes and cancer. We synthesized stable, water-soluble gold(III) complexes (Auraformin) supported by biguanide metformin or phenylmetformin for efficacious inhibition of mitochondrial respiration. The new compounds were characterized following the reaction of [C N]-cyclometalated gold(III) compounds with respective biguanides. Auraformin is solution stable in a physiologically relevant environment. We show that auraformin decreases mitochondrial respiration efficiently in comparison to the clinically used metformin by 100-fold. The compound displays significant mitochondrial uptake and induces antiproliferative activity in the micromolar range. Our results shed light on the development of new scaffolds as improved inhibitors of mitochondrial respiration.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ouro/farmacologia , Metformina/farmacologia , Mitocôndrias/efeitos dos fármacos , Compostos Organoáuricos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ouro/química , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Metformina/química , Mitocôndrias/metabolismo , Estrutura Molecular , Compostos Organoáuricos/síntese química , Compostos Organoáuricos/química , Solubilidade , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Água/químicaRESUMO
PURPOSE: To compare the outcomes of conventional surgery with the outcomes of surgeries using augmented amounts of symmetric lateral rectus recessions in the treatment of patients with basic intermittent exotropia. METHODS: One hundred seven patients were enrolled in this study; the patients were followed for more than 6 months. The study group was composed of 41 patients who had undergone conventional surgery, and 66 who had augmented surgery. The amount of recession in conventional surgery was determined according to Parks' formula; the augmented amount ranged from 1.5 to 2.5 mm more per eye in augmented surgery. RESULTS: The success rate was 68.2% in subjects who had undergone augmented surgery, compared with the 43.9% observed in those who had undergone the conventional procedure (p = 0.01). The under correction rate was 53.7% in those who had undergone conventional surgery and 30.3% in those who had undergone augmented surgery (p = 0.02). The overcorrection rate was similar in the two groups (conventional, 2.4%; augmented, 1.5%). CONCLUSIONS: The augmented formula may be preferable to the standard formula for patients undergoing symmetric surgery to correct basic intermittent exotropia.