Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
Department of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900, Monza, Italy.
Eur J Med Chem. 2017 Nov 10;140:604-614. doi: 10.1016/j.ejmech.2017.09.048. Epub 2017 Sep 23.
Antimicrobial resistance is one of the major and growing concerns in hospital- and community acquired infections, and new antimicrobial agents are therefore urgently required. It was reported that oxidative stress could contribute to the selection of resistant bacterial strains, since reactive oxygen species (ROS) revealed to be an essential driving force. In the present work 4-alkylidene-azetidinones, a new class of antibacterial agents, were functionalized with phytochemical polyphenolic acids such as protocatechuic, piperonyl, caffeic, ferulic, or sinapic acids and investigated as dual target antibacterial-antioxidant compounds. The best candidates showed good activities against multidrug resistant clinical isolates of MRSA (MICs 2-8 μg/mL). Among the new compounds, two revealed the best antioxidant capacity with TEAC-DPPH and TEAC-ABTS being significantly more active than Trolox.
抗菌耐药性是医院和社区获得性感染的主要且日益严重的问题之一,因此迫切需要新的抗菌药物。有报道称,氧化应激可能有助于耐药菌株的选择,因为活性氧(ROS)被证明是一种重要的驱动力。在本工作中,将 4-亚烷基-氮杂环丁酮这一类新型抗菌药物用植物化学多酚酸(如原儿茶酸、胡椒基、咖啡酸、阿魏酸或芥子酸)进行功能化,并将其作为双重靶标抗菌-抗氧化化合物进行研究。最佳候选化合物对多药耐药性的 MRSA 临床分离株显示出良好的活性(MICs 为 2-8μg/mL)。在新化合物中,有两种化合物表现出最好的抗氧化能力,其 TEAC-DPPH 和 TEAC-ABTS 活性明显高于 Trolox。