Liu Fang, Venter Henrietta, Bi Fangchao, Semple Susan J, Liu Jingru, Jin Chaobin, Ma Shutao
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China.
School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide 5001, Australia.
Bioorg Med Chem Lett. 2017 Aug 1;27(15):3399-3402. doi: 10.1016/j.bmcl.2017.06.005. Epub 2017 Jun 3.
5-Methylphenanthridium derivatives were designed, synthesized and evaluated for their in vitro antibacterial activity and cell division inhibitory activity against various Gram-positive and -negative bacteria. Among them, compounds 5A2, 5B1, 5B2, 5B3, 5C1 and 5C2 displayed the best on-target antibacterial activity with an MIC value of 4µg/mL against B. subtilis ATCC9372 and S. pyogenes PS, showing over 2-fold better activity than sanguinarine. The SARs showed that the 5-methylphenanthridium derivatives with the alkyl side chains at the 2-postion, especially the straight alkyl side chains exerted better on-target antibacterial activity.
设计、合成了5-甲基菲啶衍生物，并评估了它们对各种革兰氏阳性菌和阴性菌的体外抗菌活性及细胞分裂抑制活性。其中，化合物5A2、5B1、5B2、5B3、5C1和5C2表现出最佳的靶向抗菌活性，对枯草芽孢杆菌ATCC9372和化脓性链球菌PS的最低抑菌浓度（MIC）值为4μg/mL，活性比血根碱高2倍以上。构效关系表明，2-位带有烷基侧链，尤其是直链烷基侧链的5-甲基菲啶衍生物具有更好的靶向抗菌活性。
