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Synthesis of Cationic Biphen[4, 5]arenes as Biofilm Disruptors |
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| Authors: | Xinbei Du Mengke Ma Yahan Zhang Xiang Yu Longming Chen Han Zhang Zhao Meng Xueshun Jia Junyi Chen Qingbin Meng Chunju Li |
| Institution: | 1. 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 These authors contributed equally to this work.;2. State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850 P. R. China These authors contributed equally to this work.;3. State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850 P. R. China;4. 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;5. Department of Chemistry, Center for Supramolecular Chemistry and Catalysis, Shanghai University, Shanghai, 200444 P. R. China;6. Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, Ministry of Education, Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin, 300387 P. R. China |
| 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 biphenn]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. |
| Keywords: | Biofilm Disruptors Cationic Biphen[n]Arenes Cefazolin Sodium Host-Guest Complexation Synergetic Effect |