Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland.
Laboratory of Biologically Active Compounds, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland.
Molecules. 2021 Jun 14;26(12):3628. doi: 10.3390/molecules26123628.
Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibiotic antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines, and xanthine-antibiotic mixtures, towards important human pathogens , , , , , and were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8-45.6 M and enthalpy change values up to -4 kJ·M. Caffeine, used in mixtures with tested antibiotics, enhanced their antibacterial activity in most pathogens tested. However, antagonistic effects of caffeine were also observed, but only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions might be relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance.
抗菌药物耐药性是全球范围内主要的医疗保健威胁。鉴于黄嘌呤（包括咖啡因和己酮可可碱）具有良好的安全性和药理学特性，它们是药物再利用的有吸引力的候选药物。本研究旨在分析黄嘌呤与芳香族抗生素（即四环素和环丙沙星）之间的潜在相互作用及其对抗生素抗菌活性的影响。采用紫外-可见光谱法、统计热力学模型和等温滴定量热法定量评估黄嘌呤-抗生素相互作用。研究了黄嘌呤、黄嘌呤-抗生素混合物对重要人类病原体 、 、 、 、 和 的抗菌谱。咖啡因和己酮可可碱与环丙沙星和四环素直接相互作用，邻域关联常数值为 15.8-45.6 M，焓变值高达-4 kJ·M。在与测试抗生素混合使用时，咖啡因增强了大多数测试病原体的抗菌活性。然而，也观察到了咖啡因的拮抗作用，但仅在革兰阳性病原体与环丙沙星之间观察到。黄嘌呤与芳香族抗生素在分子和体外抗菌活性水平上相互作用。鉴于对咖啡因和己酮可可碱的大量暴露，这些相互作用可能与抗菌药物治疗的有效性相关，并可能有助于在多药耐药时代确定最佳治疗方案。
