Department of Medicinal Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
Eur J Med Chem. 2013 Feb;60:395-409. doi: 10.1016/j.ejmech.2012.12.027. Epub 2012 Dec 20.
Bacterial cell division occurs in conjunction with the formation of a cytokinetic Z-ring structure comprised of FtsZ subunits. Agents that can disrupt Z-ring formation have the potential, through this unique mechanism, to be effective against several of the newly emerging multi-drug resistant strains of infectious bacteria. 1- and 12-Aryl substituted benzo[c]phenanthridines have been identified as antibacterial agents that could exert their activity by disruption of Z-ring formation. Substituted 4- and 5-amino-1-phenylnaphthalenes represent substructures within the pharmacophore of these benzo[c]phenanthridines. Several 4- and 5-substituted 1-phenylnaphthalenes were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and Enterococcus faecalis. The impact of select compounds on the polymerization dynamics of S. aureus FtsZ was also assessed.
细菌细胞分裂伴随着细胞分裂的形成Z 环结构由 FtsZ 亚基组成。能够破坏 Z 环形成的药物有可能通过这种独特的机制对抗几种新出现的多药耐药性感染菌。1-和 12-芳基取代的苯并[c]菲啶已被确定为具有抗菌活性的药物,通过破坏 Z 环的形成来发挥作用。取代的 4-和 5-氨基-1-苯基萘代表这些苯并[c]菲啶的药效团中的亚结构。合成了几种 4-和 5-取代的 1-苯基萘,并评估了它们对金黄色葡萄球菌和粪肠球菌的抗菌活性。还评估了选定化合物对金黄色葡萄球菌 FtsZ 聚合动力学的影响。