Modulatory Effects of Caffeine and Pentoxifylline on Aromatic Antibiotics: A Role for Hetero-Complex Formation

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Jul 2

PMID 34198510

Citations 2

Authors

Anna Woziwodzka

Marta Krychowiak-Masnicka

Grzegorz Golunski

Anna Felberg

Agnieszka Borowik

Dariusz Wyrzykowski

Jacek Piosik

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

New Life of an Old Drug: Caffeine as a Modulator of Antibacterial Activity of Commonly Used Antibiotics.

Woziwodzka A, Krychowiak-Masnicka M, Golunski G, Losiewska A, Borowik A, Wyrzykowski D Pharmaceuticals (Basel). 2022; 15(7).

PMID: 35890171 PMC: 9315996. DOI: 10.3390/ph15070872.

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Salo V, Buchelnikov A, Evstigneev M Eur Biophys J. 2022; 51(3):297-307.

PMID: 35307756 DOI: 10.1007/s00249-022-01597-x.

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