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Supramolecular Modulation of Antibacterial Activity of Ambroxol by Cucurbit[7]uril
Author(s) -
Li Shengke,
Kuok Kit Ieng,
Ji Xia,
Xu Anni,
Yin Hang,
Zheng Jun,
Tan Huaping,
Wang Ruibing
Publication year - 2020
Publication title -
chempluschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.801
H-Index - 61
ISSN - 2192-6506
DOI - 10.1002/cplu.202000119
Subject(s) - chemistry , antibacterial activity , isothermal titration calorimetry , titration , abx test , nuclear chemistry , supramolecular chemistry , medicinal chemistry , stereochemistry , organic chemistry , crystal structure , bacteria , genetics , biology , statistics , mathematics
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 K a of (6.69±0.11)×10 5 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 (MIC 50 ) 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].