School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei, China.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5428-31. doi: 10.1016/j.bmcl.2011.06.125. Epub 2011 Jul 2.
The emergence and spread of multidrug-resistant strains of Staphylococcus aureus and Mycobacterium tuberculosis are generating a threat to public health worldwide. In the current study, a series of N(1)-benzyl and N(1)-benzyloxy-1,6-dihydro-1,3,5-triazine-2,4-diamine derivatives were synthesized and investigated for their antimicrobial activity against S. aureus, and Mycobacterium smegmatis which is taxonomically related to M. tuberculosis. Most of the compounds exhibited good activity against M. smegmatis as determined by comparison of diameters of the zone of inhibition of test compounds and standard antibiotics. Compound 7o showed potent antimycobacterial activity against M. smegmatis without mammalian DHFR inhibition liability. The results from this study indicate that 1-benzyl derivatives of 1,6-dihydro-1,3,5-triazine-2,4-diamines may be used as lead compounds for the discovery of antimycobacterial agents.
耐多药金黄色葡萄球菌和结核分枝杆菌菌株的出现和传播正在对全球公共卫生构成威胁。在本研究中，合成了一系列 N(1)-苄基和 N(1)-苯甲氧基-1,6-二氢-1,3,5-三嗪-2,4-二胺衍生物，并研究了它们对金黄色葡萄球菌和分枝杆菌的抗菌活性，分枝杆菌与结核分枝杆菌在分类上有关。通过比较测试化合物和标准抗生素的抑菌圈直径，大多数化合物对分枝杆菌表现出良好的活性。化合物 7o 对分枝杆菌具有很强的抗分枝杆菌活性，而没有哺乳动物二氢叶酸还原酶抑制作用。本研究结果表明，1,6-二氢-1,3,5-三嗪-2,4-二胺的 1-苄基衍生物可用作发现抗分枝杆菌药物的先导化合物。
