Abstract：
Since bacteria in biofilms are inherently resistant to antibiotics and biofilm-associated infections pose a serious threat to global public health, new therapeutic agents and schemes are urgently needed to meet clinical requirements. Here two quaternary ammonium-functionalized biphen[n]arenes (WBPn, n=4, 5) were designed and synthesized with excellent anti-biofilm potency. Not only could they inhibit the assembly of biofilms, but also eradicate intractable mature biofilms formed by Gram-positive S. aureus and Gram-negative E. coli bacterial strains. Moreover, they could strongly complex a conventional antibiotic, cefazolin sodium (CFZ) with complex stability constants of (7.41±0.29)×104 M-1 for CFZ/WBP4 and (4.98±0.49)×103 M-1 for CFZ/WBP5. Combination of CFZ by WBP4 and WBP5 synergistically enhanced biofilm eradication performance in vitro and statistically improved healing efficacy on E. coli-infected mice models, providing a novel supramolecular strategy for combating biofilm-associated infections.
摘要：
由于生物膜中的细菌对抗生素具有固有的抗性，并且生物膜相关感染对全球公共卫生构成严重威胁，迫切需要新的治疗药物和方案来满足临床要求。这里有两个季铵官能化的双[n]芳烃(WBPn，n=4，5）设计并合成了具有优异的抗生物膜效力。它们不仅能抑制生物膜的组装，而且还根除由革兰氏阳性金黄色葡萄球菌和革兰氏阴性大肠杆菌菌株形成的难治性成熟生物膜。此外，他们可以强烈地复合常规抗生素，头孢唑林钠（CFZ），CFZ/WBP4的复稳定常数为（7.41±0.29）×104M-1，CFZ/WBP5的复稳定常数为（4.98±0.49）×103M-1。CFZ通过WBP4和WBP5的组合在体外协同增强生物膜根除性能，并在大肠杆菌感染的小鼠模型上统计学上改善愈合功效，提供新的超分子策略来对抗生物膜相关的感染。
