Department of Chemistry, Center for Supramolecular Chemistry and Catalysis, Shanghai University, Shanghai, 200444, P. R. China.
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, P. R. China.
Angew Chem Int Ed Engl. 2023 May 15;62(21):e202301857. doi: 10.1002/anie.202301857. Epub 2023 Apr 14.
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)×10 M for CFZ/WBP4 and (4.98±0.49)×10 M 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.
由于生物膜中的细菌天生具有抗药性，生物膜相关感染对全球公共健康构成严重威胁，因此迫切需要新的治疗剂和方案来满足临床需求。这里设计并合成了两种季铵功能化联苯[n]芳烃（WBPn，n=4，5），它们具有出色的抗生物膜性能。它们不仅可以抑制生物膜的组装，还可以消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以治愈的成熟生物膜。此外，它们可以与传统抗生素头孢唑林钠（CFZ）强烈络合，其络合稳定常数分别为 7.41±0.29)×10 M 对于 CFZ/WBP4 和 (4.98±0.49)×10 M 对于 CFZ/WBP5。WBP4 和 WBP5 与 CFZ 的组合协同增强了体外生物膜清除性能，并在大肠杆菌感染小鼠模型中统计上提高了愈合效果，为对抗生物膜相关感染提供了一种新的超分子策略。
