Discovery of bicyclic inhibitors against menaquinone biosynthesis
Discovery of bicyclic inhibitors against menaquinone biosynthesis
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DOI：
10.4155/fmc.15.168
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发表时间：
2016-01-01
影响因子：
4.2
通讯作者：
Narayanasamy, Prabagaran
中科院分区：
文献类型：
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作者：
Choi, Seoung-Ryoung;Larson, Marilynn A.;Narayanasamy, Prabagaran
简介：甲萘醌用于传输电子，对于所有病原体和原核生物的有氧和无氧呼吸系统至关重要。许多革兰氏阳性细菌在电子传递系统中仅使用甲萘醌。因此，甲萘醌生物合成是开发针对细菌（包括耐药病原体）的抑制剂的潜在靶标。结果如下：在建模、合成和体外测试之后，我们确定基于7-甲氧基-2-萘酚的抑制剂靶向甲基萘醌生物合成途径的MenA酶。开发化合物1和2对结核分枝杆菌和耐甲氧西林金黄色葡萄球菌具有活性，最小抑制浓度为3-5 μ g/ml。结论：非传统的双环抑制剂，化合物1和2可以作为开发抗微生物剂的先导化合物，具有抗M.结核和耐甲氧西林的S.金黄色。
Introduction: Menaquinone is used for transporting electrons and is essential for the aerobic and anaerobic respiratory systems of all pathogens and prokaryotes. Many Gram-positive bacteria use only menaquinone in the electron transport system. Thus, menaquinone biosynthesis is a potential target for the development of inhibitors against bacteria including drug-resistant pathogens. Results: After modeling, synthesis and in vitro testing, we determined that 7-methoxy-2-naphthol-based inhibitors targeted the MenA enzyme of the menaquinone biosynthesis pathway. The developmental compounds 1 and 2 were active against Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus with a minimal inhibitory concentration of 3-5 mu g/ml. Conclusion: Nontraditional bicyclic inhibitors, compounds 1 and 2 could serve as lead compounds for the development of an antimicrobial agent, with activities against M. tuberculosis and methicillin-resistant S. aureus.