School of Life Sciences and Education, Staffordshire University, Stoke-on-Trent, Staffordshire, ST4 2DF, UK.
Department of Food Production, University of the West Indies, Frank Stockdale Building, St. Augustine, Trinidad and Tobago.
J Antibiot (Tokyo). 2020 May;73(5):299-308. doi: 10.1038/s41429-020-0280-y. Epub 2020 Jan 28.
The swift spread of infections caused by drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has quickly become a worldwide concern as infections spread from healthcare settings to the wider community. While ferrocenyl chalcones, which are chalcone derivatives with antimicrobial activity, have gained attention from researchers, further study is needed to assess their cytotoxicity. Ten newly developed chalcones, in which ring A was replaced with a ferrocenyl moiety and ring B contained increasing alkyl chain lengths from 1 to 10 carbons, were assessed. Using twofold broth microdilution, the minimum inhibitory concentration (MIC) of five of the ten compounds were lower against Gram-positive organisms (MICs from 0.008 mg ml to 0.063 mg ml) than Gram-negative organisms (MICs = 0.125 mg ml). These novel ferrocenyl chalcone compounds were effective against three types of clinically isolated drug-resistant S. aureus, including an MRSA, and against other non-resistant clinically isolated and laboratory-adapted Gram-positive bacteria. The same compounds inhibited growth in non-resistant bacteria by potentially obstructing cellular respiration in Gram-positive bacteria. Images obtained through scanning electron microscopy revealed fully lysed bacterial cells once exposed to a selected compound that showed activity. The results indicate that these newly developed compounds could be important antimicrobial agents in the treatment of infections from clinically resistant bacteria.
耐药菌感染的迅速传播,如耐甲氧西林金黄色葡萄球菌(MRSA),已经迅速成为全球关注的问题,因为感染从医疗机构传播到更广泛的社区。虽然具有抗菌活性的二茂铁查耳酮类化合物已经引起了研究人员的关注,但仍需要进一步研究来评估它们的细胞毒性。评估了十种新开发的查耳酮,其中 A 环被二茂铁取代,B 环含有从 1 到 10 个碳原子的烷基链长度增加。使用两倍肉汤微量稀释法,其中五种化合物对革兰氏阳性菌(MIC 为 0.008 mg/ml 至 0.063 mg/ml)的最低抑菌浓度(MIC)低于革兰氏阴性菌(MIC = 0.125 mg/ml)。这些新型二茂铁查耳酮化合物对三种临床分离的耐药金黄色葡萄球菌(包括耐甲氧西林金黄色葡萄球菌)和其他非耐药临床分离和实验室适应的革兰氏阳性菌有效。相同的化合物通过潜在地阻碍革兰氏阳性菌的细胞呼吸来抑制非耐药细菌的生长。通过扫描电子显微镜获得的图像显示,一旦暴露于具有活性的选定化合物,细菌细胞完全裂解。结果表明,这些新开发的化合物可能是治疗临床耐药菌感染的重要抗菌剂。