1. Supramolecular Modulation of Antibacterial Activity of Ambroxol by Cucurbit[7]uril.
- Author
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Li S, Kuok KI, Ji X, Xu A, Yin H, Zheng J, Tan H, and Wang R
- Subjects
- Ambroxol chemistry, Anti-Bacterial Agents chemistry, Bridged-Ring Compounds chemical synthesis, Dose-Response Relationship, Drug, Imidazoles chemical synthesis, Macromolecular Substances chemical synthesis, Macromolecular Substances chemistry, Microbial Sensitivity Tests, Molecular Conformation, Ambroxol pharmacology, Anti-Bacterial Agents pharmacology, Bridged-Ring Compounds chemistry, Escherichia coli drug effects, Imidazoles chemistry, Pseudomonas aeruginosa drug effects
- Abstract
Supramolecular encapsulation by cucurbit[7]uril (CB[7]) was recently demonstrated to provide a simple and efficient method for antibacterial activity regulation of antibiotics. In this work, CB[7] was shown to form binary host-guest complex with ambroxol hydrochloride (ABX), a clinical mucokinetic and expectorant drug, which was reported to exhibit certain antibacterial activity.
1 H NMR titration and isothermal titration calorimetry experiment results suggested that the 4-hydroxyl cyclohexylamine group of ABX was included inside the CB[7] cavity, with a binding constant Ka of (6.69±0.11)×105 M-1 in phosphate buffered saline (PBS) solution, thermodynamically driven by both enthalpy change (ΔH=-12.2 kJ/mol) and entropy change (TΔS=21.1 kJ/mol). More importantly, ABX's inhibitory activity (MIC50 ) against bacillary strains towards Pseudomonas aeruginosa and Escherichia coli strains was decreased from (5.11±0.31)×10-6 M-1 and (2.63±0.34)×10-5 M-1 to zero upon encapsulation by CB[7], and was subsequently recovered to almost its original activity when a competitive guest, amantadine hydrochloride, for disassembling CB[7]-ABX complex, was added, suggesting that the antibacterial activity of ABX could be readily "turned off/on" upon its complexation and decomplexation with CB[7]., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2020
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