State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, 999078, China.
Key Laboratory of Mesoscopic Chemistry of MOE, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
Angew Chem Int Ed Engl. 2021 Jan 11;60(2):618-623. doi: 10.1002/anie.202013975. Epub 2020 Dec 8.
Due to the inherent resistance of bacterial biofilms to antibiotics and their serious threat to global public health, novel therapeutic agents and strategies to tackle biofilms are urgently needed. To this end, we designed and synthesized a novel guanidinium-functionalized pillar[5]arene (GP5) that exhibited high antibacterial potency against Gram-negative E. coli (BH101) and Gram-positive S. aureus (ATCC25904) strains. More importantly, GP5 effectively disrupted preformed E. coli biofilms by efficient penetration through biofilm barriers and subsequent destruction of biofilm-enclosed bacteria. Furthermore, host-guest complexation between GP5 and cefazolin sodium, a conventional antibiotic that otherwise shows negligible activity against biofilms, exhibited much enhanced, synergistic disruption activity against E. coli biofilms, thus providing a novel supramolecular platform to effectively disrupt biofilms.
由于细菌生物膜对抗生素的固有耐药性及其对全球公众健康的严重威胁，因此迫切需要新型治疗剂和策略来解决生物膜问题。为此，我们设计并合成了一种新型的胍基功能化的柱[5]芳烃（GP5），其对革兰氏阴性大肠杆菌（BH101）和革兰氏阳性金黄色葡萄球菌（ATCC25904）菌株具有很高的抗菌活性。更重要的是，GP5 能够有效地穿透生物膜屏障并随后破坏生物膜包裹的细菌，从而有效破坏已形成的大肠杆菌生物膜。此外，GP5 与头孢唑林钠（一种常规抗生素，对生物膜几乎没有活性）之间的主客体络合作用表现出对大肠杆菌生物膜更强的协同破坏活性，从而为有效破坏生物膜提供了一种新的超分子平台。
