Liu X L, Xu Y J, Go M L
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Eur J Med Chem. 2008 Aug;43(8):1681-7. doi: 10.1016/j.ejmech.2007.10.007. Epub 2007 Oct 11.
A library of chalcones with basic functionalities were evaluated for antibacterial activity against drug sensitive strains of Staphylococcus aureus and Escherichia coli. The most active compounds were 2-52 and 2-57 (MIC 6.3 microM S. aureus). These compounds had no activity against E. coli (MIC>100 microM). Both compounds were characterized by a ring A that was substituted with 2-hydroxy-4,6-dimethoxy-3-(1-methylpiperidin-4-yl) groups. The phenolic OH and 1-methylpiperidinyl groups were required for activity but the phenolic OH may play a more critical role. While the compounds were comparable to licochalcone A in terms of antibacterial activity, they caused less hemolysis of sheep erythrocytes at high concentrations (100 microM). It was noted that the structural requirements for limiting hemolytic activity were less stringent than those required for antibacterial activity. The present findings suggest that the chalcone framework is an attractive template for optimization to achieve better potency, lower toxicity and a wider spectrum of antibacterial activity.
对一系列具有基本官能团的查尔酮进行了评估，以检测其对金黄色葡萄球菌和大肠杆菌药物敏感菌株的抗菌活性。活性最高的化合物是2-52和2-57（对金黄色葡萄球菌的最低抑菌浓度为6.3微摩尔）。这些化合物对大肠杆菌无活性（最低抑菌浓度>100微摩尔）。这两种化合物的特征是A环被2-羟基-4,6-二甲氧基-3-(1-甲基哌啶-4-基)基团取代。酚羟基和1-甲基哌啶基对活性是必需的，但酚羟基可能起更关键的作用。虽然这些化合物在抗菌活性方面与甘草查尔酮A相当，但在高浓度（100微摩尔）时它们对绵羊红细胞的溶血作用较小。值得注意的是，限制溶血活性的结构要求不如抗菌活性要求严格。目前的研究结果表明，查尔酮骨架是一个有吸引力的模板，可用于优化以实现更好的效力、更低的毒性和更广泛的抗菌活性谱。
