Academic Journal
In vitro effects of pH variation and immune-induced copper accumulation on the antibacterial and cytotoxic activity of levofloxacin during Streptococcus pneumoniae infection.
| Τίτλος: | In vitro effects of pH variation and immune-induced copper accumulation on the antibacterial and cytotoxic activity of levofloxacin during Streptococcus pneumoniae infection. |
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| Συγγραφείς: | Labović M; Department of General Practice, Centre for Military Medical Institutions 'Slavija', Belgrade, Serbia; Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia., Milenković MR; University of Belgrade, Faculty of Chemistry, Belgrade, Serbia., Bajuk-Bogdanović D; University of Belgrade, Faculty of Physical Chemistry, Belgrade, Serbia., Milenković MT; Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia., Gligorijević N; Institute for Oncology and Radiology of Serbia, Belgrade, Serbia., Popović Bijelić A; University of Belgrade, Faculty of Physical Chemistry, Belgrade, Serbia., Božić Cvijan B; Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: bojana.bozic@med.bg.ac.rs., Korać Jačić J; Department of Life Sciences, Institute for Multidisciplinary Research, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia. Electronic address: jskorac@imsi.bg.ac.rs. |
| Πηγή: | Bioorganic chemistry [Bioorg Chem] 2026 Aug 15; Vol. 178, pp. 109947. Date of Electronic Publication: 2026 May 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| Ιατρικοί όροι (MeSH): | Copper*/metabolism , Copper*/chemistry , Copper*/pharmacology , Levofloxacin*/pharmacology , Levofloxacin*/chemistry , Anti-Bacterial Agents*/pharmacology , Anti-Bacterial Agents*/chemistry , Anti-Bacterial Agents*/chemical synthesis , Streptococcus pneumoniae*/drug effects , Pneumococcal Infections*/drug therapy , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry, Coordination Complexes/pharmacology ; Coordination Complexes/chemistry ; Cell Survival/drug effects ; Hydrogen-Ion Concentration ; Humans ; Microbial Sensitivity Tests ; Dose-Response Relationship, Drug ; Structure-Activity Relationship ; Molecular Structure |
| Περίληψη: | Copper is an essential trace redox active metal and its concentration in human body is increased during infections. Given the potential for copper ions to modulate antibiotic activity, this study investigates the interactions between Cu2+ and levofloxacin (LVX) in vitro, under pH conditions representative of S. pneumoniae-induced pneumonia, with subsequent assessment of the resulting antibacterial and cytotoxic effects. Complex formation between Cu2+ and LVX is observed at both, physiological (pH 7.4), as well as in acidic conditions (pH 4) associated with the metabolic activity of S. pneumoniae. At both investigated pHs monoligand and bisligand Cu2+ complexes of LVX were detected by UV-Vis, EPR and cyclic voltammetry. Their abundance depends on pH and molar ratio of LVX and Cu2+. The physiological pH 7.4 and higher LVX/Cu2+ molar ratios shift equilibrium toward formation of bisligand complex. In both complexes Cu2+ coordinates with LVX through the carboxylic and β-keto oxygen atoms. The effect of Cu2+ coordination with LVX on its antibacterial and cytotoxic activity were investigated. Formation of Cu2+-LVX complexes enhance antibacterial activity of LVX against S. pneumoniae, E. coli, and K. pneumoniae at both pH values, but reduce activity against S. aureus compared to LVX alone. Additionally, Cu2+-LVX complexes exhibit higher cytotoxicity toward normal lung fibroblasts than A549 carcinoma cells with a more pronounced effect under acidic conditions. In vitro evaluation of antibacterial and cytotoxic activity of LVX in the presence of Cu2+ ions highlights the Janus-faced behavior of the Cu2+-LVX complexes, characterized by simultaneous beneficial improvement of antimicrobial activity and harmful cytotoxicity to lung fibroblasts. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Antibacterial activity; Complex; Copper; Cytotoxicity; Levofloxacin |
| Substance Nomenclature: | 789U1901C5 (Copper) 6GNT3Y5LMF (Levofloxacin) 0 (Anti-Bacterial Agents) 0 (Coordination Complexes) 0 (Antineoplastic Agents) |
| Entry Date(s): | Date Created: 20260513 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260717 |
| DOI: | 10.1016/j.bioorg.2026.109947 |
| PMID: | 42127742 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2026.109947 |