Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, China.
The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Bioorg Med Chem Lett. 2018 Jun 1;28(10):1825-1831. doi: 10.1016/j.bmcl.2018.04.015. Epub 2018 Apr 7.
A novel series of 5-methyl-2-phenylphenanthridium derivatives were displayed outstanding activity against a panel of antibiotic-sensitive and -resistant bacteria strains compared with their precursor sanguinarine, ciprofloxacin and oxacillin sodium. Compounds 7 l, 7m and 7n were found to display the most effective activity against five sensitive strains (0.06-2 μg/mL) and three resistant strains (0.25-4 μg/mL). The kinetic profiles indicated that compound 7l possessed the strongest bactericidal effect on S. aureus ATCC25923, with the MBC value of 16 μg/mL. The cell morphology and the FtsZ polymerization assays indicated that these compounds inhibited the bacterial proliferation by interfering the function of bacterial FtsZ. The SARs showed that all the 4-methyl-substituted 5-methyl-2-phenylphenanthridium subseries could be further investigated as the FtsZ-targeting antibacterial agents.
一系列新型 5-甲基-2-苯基菲啶衍生物与它们的前体血根碱、环丙沙星和苯唑西林钠相比，对一系列抗生素敏感和耐药的细菌株表现出优异的活性。化合物 7l、7m 和 7n 被发现对五种敏感菌株（0.06-2μg/mL）和三种耐药菌株（0.25-4μg/mL）显示出最有效的活性。动力学分析表明，化合物 7l 对金黄色葡萄球菌 ATCC25923 具有最强的杀菌作用，MBC 值为 16μg/mL。细胞形态和 FtsZ 聚合试验表明，这些化合物通过干扰细菌 FtsZ 的功能来抑制细菌的增殖。SAR 表明，所有的 4-甲基取代的 5-甲基-2-苯基菲啶亚系列都可以进一步作为针对 FtsZ 的抗菌药物进行研究。
