RESUMO
Several regulatory systems contribute to bacterial resistance to heavy metals controlling the expression of factors required to eliminate the intoxicant and/or to repair the damage caused by it. In Salmonella, the response to Au ions is mediated by the specific metalloregulator GolS that, among other genes, controls the expression of the RND-efflux pump GesABC. In this work, we demonstrate that CpxR/CpxA, a main cell-envelope stress-responding system, promotes gesABC transcription in the presence of Au ions at neutral pH. Deletion of either cpxA or cpxR, or mutation of the CpxR-binding site identified upstream of the GolS-operator in the gesABC promoter region reduces but does not abrogate the GolS- and Au-dependent activation of gesABC. Au also triggers the activation of the CpxR/CpxA system and deletion of the cpxRA operon severely reduces survival in the presence of the toxic metal. Our results indicate that the coordinated action of GolS and CpxR/CpxA contribute to protecting the cell from severe Au damage.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Regulação Bacteriana da Expressão Gênica , Ouro/farmacologia , Salmonella enterica/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Óperon , Proteínas Quinases/metabolismo , Salmonella enterica/genéticaRESUMO
Levoglucosenone has been used as template for the synthesis of a wide variety of compounds with an impressive structural variability. However, scarce work has been done regarding the generation of new bioactive entities. Here we report the cytotoxic effect of levoglucosenone and some related derivatives against hepatocarcinoma cell lines. Compounds were obtained in only one synthetic step and one of them showed an activity within the range of IC50 values of cisplatin, a frequently administered chemotherapy drug.
Assuntos
Antineoplásicos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Glucose/análogos & derivados , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glucose/síntese química , Glucose/química , Glucose/toxicidade , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologiaRESUMO
The effect of an extra EWG in the reactivity and regioselectivity in Diels-Alder reactions of ß-cyanolevoglucosenone and 4 different dienes was studied by a joint computational and experimental study. Conceptual DFT analysis successfully predicted an important enhancement in the reactivity, and correctly anticipated the regioselectivity in the reactions with isoprene. However, this static treatment failed when dealing the regiochemical preference of the reactions involving a substituted anthracene as diene. MPW1K/6-31G* calculations correctly reproduced the experimental observations. Based on the collected data, we found that when dealing with dienes and dienophiles with no clear electronically activated position, the ease of pyramidalization of the interacting atoms dictates the regioselectivity of the DA reaction.