The invention provides a compound of formula I:or a salt thereof, wherein R
3
-R
8
and X and Y have any of the values described in the specification, as well as compositions comprising a compound of formula I. The compounds are useful as antibacterial agents.
Substituted 1,6-diphenylnaphthalenes as FtsZ-targeting antibacterial agents
作者:Yongzheng Zhang、Daniel Giurleo、Ajit Parhi、Malvika Kaul、Daniel S. Pilch、Edmond J. LaVoie
DOI:10.1016/j.bmcl.2013.02.016
日期:2013.4
mammalian β-tubulin was also assessed. The presence of a basic functional group or a quaternary ammonium substituent on the 6-phenylnaphthalene was required for significant antibacterial activity. Diphenylnaphthalene derivatives that were active as antibiotics, did exert a pronounced effect on bacterial FtsZ polymerization and do not appear to cross-react with mammalian tubulin to any significant degree.
细菌细胞分裂与由 FtsZ 亚基组成的细胞因子 Z 环结构的形成一起发生。通过这种独特的机制,破坏 Z 环形成的药剂有可能对几种新出现的多重耐药感染性细菌菌株有效。几种 1-苯基苯并 [c] 菲啶表现出显着的抗菌活性。基于它们与这些化合物的结构相似性,合成了一系列不同的取代 1,6-二苯基萘,并评估其对金黄色葡萄球菌和粪肠球菌的抗菌活性。此外,还评估了选择的 1,6-二苯基萘对金黄色葡萄球菌 FtsZ 和哺乳动物 β-微管蛋白聚合动力学的影响。6-苯基萘上存在碱性官能团或季铵取代基是显着抗菌活性所必需的。具有抗生素活性的二苯基萘衍生物确实对细菌 FtsZ 聚合产生显着影响,并且似乎不会与哺乳动物微管蛋白发生任何显着程度的交叉反应。