{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:23:11Z","timestamp":1790112191297,"version":"4.0.1"},"reference-count":99,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Copper (Cu) is an essential trace metal and its concentration in body plasma is tightly regulated. An increase in Cu concentration in body fluids is observed in numerous pathological conditions, including infections caused by microorganisms. Evidence shows that Cu ions can impact the activity of antibiotics by increasing efficiency or diminishing\/neutralizing antibiotic activity, forming complexes which may lead to antibiotic structure degradation. Herein, we represent the evidence available on Cu\u2013antibiotic interactions and their possible impact on antimicrobial therapy efficiency. So far, in vitro studies described interactions between Cu ions and the majority of antibiotics in clinical use: penicillins, cephalosporins, carbapenems, macrolides, aminoglycosides, tetracyclines, fluoroquinolones, isoniazid, metronidazole. In vitro-described degradation or lower antimicrobial activity of amoxicillin, ampicillin, cefaclor, ceftriaxone, and meropenem in the presence of Cu ions suggest caution when using prescribed antibiotics in patients with altered Cu levels. On the other hand, several Cu-dependent compounds with antibacterial activity including the drug-resistant bacteria were discovered, such as thiosemicarbazones, disulfiram, dithiocarbamates, 8-hydroxiquinoline, phenanthrolines, pyrithione. Having in mind that the development of new antibiotics is already marked as inadequate and does not meet global needs, the potential of Cu\u2013antibiotic interactions to change the efficiency of antimicrobial therapy requires further investigation.<\/jats:p>","DOI":"10.3390\/molecules28135133","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:53:16Z","timestamp":1688345596000},"page":"5133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["The Impact of Copper Ions on the Activity of Antibiotic Drugs"],"prefix":"10.3390","volume":"28","author":[{"given":"Bojana","family":"Bo\u017ei\u0107 Cvijan","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Kora\u0107 Ja\u010di\u0107","sequence":"additional","affiliation":[{"name":"Life Sciences Department, Institute for Multidisciplinary Research, University of Belgrade, Kneza Vi\u0161eslava 1, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Baj\u010deti\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinical Pharmacology Unit, University Children\u2019s Hospital, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/bs.ampbs.2017.01.007","article-title":"Copper and Antibiotics: Discovery, Modes of Action, and Opportunities for Medicinal Applications","volume":"70","author":"Dalecki","year":"2017","journal-title":"Adv. Microb. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrd3975","article-title":"Platforms for antibiotic discovery","volume":"12","author":"Lewis","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","unstructured":"Antimicrobial Resistance Collaborators (2022). Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet, 399, 629\u2013655."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8955","DOI":"10.1038\/s41598-020-65978-y","article-title":"A copper-dependent compound restores ampicillin sensitivity in multidrug-resistant Staphylococcus aureus","volume":"10","author":"Crawford","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.freeradbiomed.2018.09.038","article-title":"Coordination and redox interactions of \u03b2-lactam antibiotics with Cu2+ in physiological settings and the impact on antibacterial activity","volume":"129","author":"Pristov","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1007\/s10620-007-0043-7","article-title":"Serum copper, ceruloplasmin and 24-h urine copper evaluations in celiac patients","volume":"53","author":"Ince","year":"2008","journal-title":"Dig. Dis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"594529","DOI":"10.4061\/2011\/594529","article-title":"Copper and Its Complexes in Medicine: A Biochemical Approach","volume":"2011","author":"Iakovidis","year":"2011","journal-title":"Mol. Biol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1742-1241.2007.01643.x","article-title":"The relationship between serum copper and ceruloplasmin in routine clinical practice","volume":"62","author":"Twomey","year":"2008","journal-title":"Int. J. Clin. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1373\/clinchem.2004.031773","article-title":"Serum copper is decreased in premature newborns and increased in newborns with hemolytic jaundice","volume":"50","author":"Schulpis","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/978-1-4614-3573-0_9","article-title":"Reaction mechanism of mammalian mitochondrial cytochrome c oxidase","volume":"748","author":"Yoshikawa","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0945-053X(98)90012-9","article-title":"Lysyl oxidase: Properties, regulation and multiple functions in biology","volume":"16","author":"Kagan","year":"1998","journal-title":"Matrix Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev.biochem.72.121801.161647","article-title":"Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis","volume":"74","author":"Valentine","year":"2005","journal-title":"Annu. Rev. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1021\/ar500460z","article-title":"Inhibition and oxygen activation in copper amine oxidases","volume":"48","author":"Shepard","year":"2015","journal-title":"Acc. Chem. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.bioelechem.2009.09.007","article-title":"Do copper ions activate tyrosinase enzyme? A biosensor model for the solution","volume":"78","author":"Akyilmaz","year":"2010","journal-title":"Bioelectrochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/iub.1614","article-title":"Dissecting copper homeostasis in diabetes mellitus","volume":"69","author":"Lowe","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1007\/s12011-014-0046-0","article-title":"Association of serum levels of iron, copper, and zink, and inflammatory markers with bacteriological sputum conversion during tuberculosis treatment","volume":"160","author":"Moraes","year":"2014","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jtemb.2016.02.006","article-title":"Dietary copper and human health: Current evidence and unresolved issues","volume":"35","author":"Bost","year":"2016","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"614S","DOI":"10.1093\/ajcn\/85.2.614S","article-title":"Nutrition and the developing brain: Nutrient priorities and measurement","volume":"85","author":"Georgieff","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0300-483X(99)00178-X","article-title":"A comparison of hepatocyte cytotoxic mechanisms for Cu2+ and Cd2+","volume":"143","author":"Pourahmad","year":"2000","journal-title":"Toxicology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2174\/187152712799960709","article-title":"Nanoparticle Delivery of Transition-Metal Chelators to the Brain: Oxidative Stress will Never See it Coming! CNS Neurol Disord Drug Targets","volume":"11","author":"Bonda","year":"2012","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.lfs.2017.10.013","article-title":"Current insights on the role of iron and copper dyshomeostasis in the pathogenesis of bilirubin neurotoxicity","volume":"191","author":"Viktorinova","year":"2017","journal-title":"Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1128\/AEM.02766-10","article-title":"Metallic copper as an antimicrobial surface","volume":"77","author":"Grass","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrmicro3028","article-title":"Antimicrobial activity of metals: Mechanisms, molecular targets and applications","volume":"11","author":"Lemire","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/18756786MTA4iMTAi3","article-title":"Antimicrobial Applications of Nanoliposome Encapsulated Silver Nanoparticles: A Potential Strategy to Overcome Bacterial Resistance","volume":"17","author":"Mozafari","year":"2021","journal-title":"Curr. Nanosci."},{"key":"ref_25","first-page":"4467","article-title":"Synthesis, characterization, and antimicrobial properties of copper nanoparticles","volume":"8","author":"Usman","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0300-483X(03)00159-8","article-title":"Copper toxicity, oxidative stress, and antioxidant nutrients","volume":"189","author":"Gaetke","year":"2003","journal-title":"Toxicology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7242","DOI":"10.1128\/JB.00837-06","article-title":"Survival and growth in the presence of elevated copper: Transcriptional profiling of copper-stressed Pseudomonas aeruginosa","volume":"188","author":"Teitzel","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1006\/abbi.1993.1074","article-title":"The pecking order of free radicals and antioxidants: Lipid peroxidation, alpha-tocopherol, and ascorbate","volume":"300","author":"Buettner","year":"1993","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1111\/j.1462-2920.2009.01973.x","article-title":"Chromosomal antioxidant genes have metal ion-specific roles as determinants of bacterial metal tolerance","volume":"11","author":"Harrison","year":"2009","journal-title":"Environ. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8344","DOI":"10.1073\/pnas.0812808106","article-title":"The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity","volume":"106","author":"Macomber","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1111\/jam.13681","article-title":"Contact killing and antimicrobial properties of copper","volume":"124","author":"Vincent","year":"2018","journal-title":"J. Appl. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6444","DOI":"10.1128\/AAC.01289-15","article-title":"Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics","volume":"59","author":"Djoko","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1128\/AAC.02316-13","article-title":"Copper complexation screen reveals compounds with potent antibiotic properties against methicillin-resistant Staphylococcus aureus","volume":"58","author":"Haeili","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4835","DOI":"10.1128\/AAC.00692-15","article-title":"Disulfiram and Copper Ions Kill Mycobacterium tuberculosis in a Synergistic Manner","volume":"59","author":"Dalecki","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5765","DOI":"10.1128\/AAC.00325-16","article-title":"8-Hydroxyquinolines Are Boosting Agents of Copper-Related Toxicity in Mycobacterium tuberculosis","volume":"60","author":"Shah","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1007\/s42770-020-00351-9","article-title":"Antimicrobial action of 1,10-phenanthroline-based compounds on carbapenemase-producing Acinetobacter baumannii clinical strains: Efficacy against planktonic- and biofilm-growing cells","volume":"51","author":"Ventura","year":"2020","journal-title":"Braz. J. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1039\/c8mt00316e","article-title":"Pyrazolopyrimidinones, a novel class of copper-dependent bacterial antibiotics against multi-drug resistant S. aureus","volume":"11","author":"Crawford","year":"2019","journal-title":"Metallomics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5851","DOI":"10.1128\/AAC.01106-15","article-title":"Inhibition of aminoglycoside 6\u2032-N-acetyltransferase type Ib-mediated amikacin resistance in Klebsiella pneumoniae by zinc and copper pyrithione","volume":"59","author":"Chiem","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1039\/C3MT00348E","article-title":"Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action","volume":"6","author":"Djoko","year":"2014","journal-title":"Metallomics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5753","DOI":"10.1128\/AAC.00724-11","article-title":"Zinc pyrithione inhibits yeast growth through copper influx and inactivation of iron-sulfur proteins","volume":"55","author":"Reeder","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1039\/C2DT32392C","article-title":"The antimicrobial properties of some copper(II) and platinum(II) 1,10-phenanthroline complexes","volume":"42","author":"Ng","year":"2013","journal-title":"Dalton Trans."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s00775-021-01922-3","article-title":"Copper(II) and silver(I)-1,10-phenanthroline-5,6-dione complexes interact with double-stranded DNA: Further evidence of their apparent multi-modal activity towards Pseudomonas aeruginosa","volume":"27","author":"Galdino","year":"2022","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.cbi.2006.08.025","article-title":"In vitro anti-tumour effect of 1,10-phenanthroline-5,6-dione (phendione), [Cu(phendione)3](ClO4)2.4H2O and [Ag(phendione)2]ClO4 using human epithelial cell lines","volume":"164","author":"Deegan","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"aad3292","DOI":"10.1126\/science.aad3292","article-title":"Multidrug evolutionary strategies to reverse antibiotic resistance","volume":"351","author":"Baym","year":"2016","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"112829","DOI":"10.1016\/j.ejmech.2020.112829","article-title":"\u03b2-lactam antibiotics: An overview from a medicinal chemistry perspective","volume":"208","author":"Lima","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"De Rosa, M., Verdino, A., Soriente, A., and Marabotti, A. (2021). The Odd Couple(s): An Overview of Beta-Lactam Antibiotics Bearing More Than One Pharmacophoric Group. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020617"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/S1526-9523(02)00330-6","article-title":"The penicillins: A review and update","volume":"47","author":"Miller","year":"2002","journal-title":"J. Midwifery Womens Health."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0463.2009.02563.x","article-title":"Beta-lactam antibiotics: From antibiosis to resistance and bacteriology","volume":"118","author":"Kong","year":"2010","journal-title":"APMIS"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1042\/bj0790377","article-title":"The structure of cephalosporin C","volume":"79","author":"Abraham","year":"1961","journal-title":"Biochem. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jinorgbio.2016.11.028","article-title":"Enhancement of antibiotic-activity through complexation with metal ions\u2014Combined ITC, NMR, enzymatic and biological studies","volume":"167","author":"Kolmar","year":"2017","journal-title":"J. Inorg. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1111\/j.2042-7158.1966.tb07813.x","article-title":"Complexation of penicillins and penicilloic acids by cupric ion","volume":"18","author":"Cressman","year":"1966","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/j.2042-7158.1966.tb07794.x","article-title":"Metal binding tendencies of various antibiotics","volume":"18","author":"Niebergall","year":"1966","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1134\/S0036023609070122","article-title":"Copper(II) complexation with ampicillin, amoxicillin, and cephalexin","volume":"54","author":"Lapshin","year":"2009","journal-title":"Russ. J. Inorg. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4279","DOI":"10.1007\/s11356-017-0524-y","article-title":"Cu(II)-catalyzed degradation of ampicillin: Effect of pH and dissolved oxygen","volume":"25","author":"Guo","year":"2018","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1080\/14756360310001624939","article-title":"Metalloantibiotics: Synthesis and antibacterial activity of cobalt(II), copper(II), nickel(II) and zinc(II) complexes of kefzol","volume":"19","author":"Chohan","year":"2004","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1080\/00958970903494157","article-title":"Metal chelates of ampicillin versus amoxicillin: Synthesis, structural investigation, and biological studies","volume":"63","year":"2010","journal-title":"J. Coord. Chem."},{"key":"ref_57","first-page":"555","article-title":"Characterization and activity of cephalosporin metal complexes","volume":"63","author":"Auda","year":"2008","journal-title":"Pharmazie"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1080\/00958970410001721411","article-title":"Synthesis and antibacterial activity of cephalexin metal complexes","volume":"57","author":"Anacona","year":"2004","journal-title":"J. Coord. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1080\/00958970500393208","article-title":"Synthesis and antibacterial activity of cephradine metal complexes","volume":"59","author":"Anacona","year":"2005","journal-title":"J. Coord. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s11243-008-9074-y","article-title":"Synthesis and antibacterial activity of copper(II) complexes with sulphathiazole and cephalosporin ligands","volume":"33","author":"Anacona","year":"2008","journal-title":"Transit. Met. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.saa.2010.09.025","article-title":"Synthesis, spectral, thermal and antimicrobial studies of some new tri metallic biologically active ceftriaxone complexes","volume":"78","author":"Ali","year":"2011","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3390\/ph2030184","article-title":"Effect of Different Metal Ions on the Biological Properties of Cefadroxil","volume":"2","author":"Auda","year":"2009","journal-title":"Pharmaceuticals"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.saa.2007.09.008","article-title":"Copper(II) complexes with bioactive carboxyamide: Synthesis, characterization and biological activity","volume":"70","author":"Singh","year":"2008","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/14756360310001623318","article-title":"Binding of Transition Metal Ions [Cobalt, Copper, Nickel and Zinc] with Furanyl-, Thiophenyl-, Pyrrolyl-, Salicylyland Pyridyl-Derived Cephalexins as Potent Antibacterial Agents","volume":"19","author":"Chohan","year":"2004","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Djoko, K.Y., Achard, M.E.S., Phan, M.D., Lo, A.W., Miraula, M., Prombhul, S., Hancock, S.J., Peters, K.M., Sidjabat, H.E., and Harris, P.N. (2018). Copper Ions and Coordination Complexes as Novel Carbapenem Adjuvants. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.02280-17"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Aurilio, C., Sansone, P., Barbarisi, M., Pota, V., Giaccari, L.G., Coppolino, F., Barbarisi, A., Passavanti, M.B., and Pace, M.C. (2022). Mechanisms of Action of Carbapenem Resistance. Antibiotics, 11.","DOI":"10.3390\/antibiotics11030421"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.envpol.2013.05.043","article-title":"Interactions of tetracycline with Cd (II), Cu (II) and Pb (II) and their cosorption behavior in soils","volume":"180","author":"Zhao","year":"2013","journal-title":"Environ. Pollut."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1128\/MMBR.65.2.232-260.2001","article-title":"Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance","volume":"65","author":"Chopra","year":"2001","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.tim.2017.04.010","article-title":"At the Nexus of Antibiotics and Metals: The Impact of Cu and Zn on Antibiotic Activity and Resistance","volume":"25","author":"Poole","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1007\/s10646-014-1383-7","article-title":"Joint toxicity of tetracycline with copper(II) and cadmium(II) to Vibrio fischeri: Effect of complexation reaction","volume":"24","author":"Tong","year":"2015","journal-title":"Ecotoxicology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jinorgbio.2014.05.007","article-title":"Fluoroquinolone-metal complexes: A route to counteract bacterial resistance?","volume":"138","author":"Feio","year":"2014","journal-title":"J. Inorg. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jinorgbio.2012.02.003","article-title":"Synthesis, characterization and antibacterial studies of a copper(II) levofloxacin ternary complex","volume":"110","author":"Sousa","year":"2012","journal-title":"J. Inorg. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.jinorgbio.2010.03.017","article-title":"Solution and biological behaviour of enrofloxacin metalloantibiotics: A route to counteract bacterial resistance?","volume":"104","author":"Saraiva","year":"2010","journal-title":"J. Inorg. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jinorgbio.2013.10.013","article-title":"Synthesis, characterization and antibacterial studies of a copper(II) lomefloxacin ternary complex","volume":"131","author":"Fernandes","year":"2014","journal-title":"J. Inorg. Biochem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.jinorgbio.2007.12.011","article-title":"Copper(II) complexes with sparfloxacin and nitrogen-donor heterocyclic ligands: Structure-activity relationship","volume":"102","author":"Efthimiadou","year":"2008","journal-title":"J. Inorg. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.bmc.2009.12.037","article-title":"Square pyramidal copper(II) complexes with forth generation fluoroquinolone and neutral bidentate ligand: Structure, antibacterial, SOD mimic and DNA-interaction studies","volume":"18","author":"Patel","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1128\/AAC.44.12.3249-3256.2000","article-title":"Aminoglycosides: Perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicrob","volume":"44","author":"Kotra","year":"2000","journal-title":"Agents Chemother."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1021\/ic025965t","article-title":"Solution chemistry of copper(II)-gentamicin complexes: Relevance to metal-related aminoglycoside toxicity","volume":"42","author":"Lesniak","year":"2003","journal-title":"Inorg. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1002\/pro.437","article-title":"Crystal structure and kinetic mechanism of aminoglycoside phosphotransferase-2\u2033-IVa","volume":"19","author":"Toth","year":"2010","journal-title":"Protein Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1155\/S1565363304000056","article-title":"Oxidative activity of copper(II) complexes with aminoglycoside antibiotics as implication to the toxicity of these drugs","volume":"2","author":"Szczepanik","year":"2004","journal-title":"Bioinorg. Chem. Appl."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0891-5849(98)00037-9","article-title":"Iron chelators protect from aminoglycoside-induced cochleo- and vestibulo-toxicity","volume":"25","author":"Song","year":"1998","journal-title":"Free Radic. Biol. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0162-0134(03)00029-1","article-title":"In vitro oxidative activity of cupric complexes of kanamycin A in comparison to in vivo bactericidal efficacy","volume":"94","author":"Szczepanik","year":"2003","journal-title":"J. Inorg. Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1080\/00032718908052388","article-title":"Coordination chemical studies of some polymeric transition metal complexes with neomycin and their biological activity uses. Indirect determination of neomycin by atomic absorption spectroscopy (AAS)","volume":"22","author":"Issa","year":"1989","journal-title":"Anal. Lett."},{"key":"ref_84","first-page":"571","article-title":"Interactions of metronidazole with other medicines: A brief review","volume":"69","author":"Miljkovic","year":"2014","journal-title":"Pharmazie"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.molstruc.2015.02.057","article-title":"Coordination of metronidazole to Cu(II): Structural characterization of a mononuclear square-planar compound","volume":"1091","author":"Palmer","year":"2015","journal-title":"J. Mol. Struct."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0162-0134(02)00468-3","article-title":"Supramolecular structures of metronidazole and its copper(II), cobalt(II) and zinc(II) coordination compounds","volume":"91","author":"Vicente","year":"2002","journal-title":"J. Inorg. Biochem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5446","DOI":"10.1080\/07391102.2020.1871072","article-title":"Novel copper complexes of metronidazole and metronidazole benzoate: Synthesis, characterization, biological and computational studies","volume":"40","author":"Rafique","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Wijesekara, P.N.K., Kumbukgolla, W.W., Jayaweera, J.A.A.S., and Rawat, D. (2017). Review on Usage of Vancomycin in Livestock and Humans: Maintaining Its Efficacy, Prevention of Resistance and Alternative Therapy. Vet. Sci., 4.","DOI":"10.3390\/vetsci4010006"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3808","DOI":"10.1039\/b508662k","article-title":"Unusual binding ability of vancomycin towards Cu2+ ions","volume":"23","author":"Swiatek","year":"2005","journal-title":"Dalton Trans."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1021\/jm00143a021","article-title":"Structure of a copper-isoniazid complex","volume":"24","author":"Hanson","year":"1981","journal-title":"J. Med. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"458","DOI":"10.7164\/antibiotics.33.458","article-title":"Green and purple copper (II)-chloramphenicol complexes in methanol: Evidence for the coordination of deprotonated amide nitrogen","volume":"33","author":"Sakurai","year":"1980","journal-title":"J. Antibiot."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0162-0134(01)00167-2","article-title":"Copper(II)-lincomycin: Complexation pattern and oxidative activity","volume":"84","author":"Lesniak","year":"2001","journal-title":"J. Inorg. Biochem."},{"key":"ref_93","first-page":"223","article-title":"Comparative in vitro investigations of the interaction between some macrolides and Cu(II), Zn(II) and Fe(II)","volume":"58","author":"Hamdan","year":"2003","journal-title":"Pharmazie"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"121035","DOI":"10.1016\/j.envpol.2023.121035","article-title":"Evaluating the impact of heavy metals on antimicrobial resistance in the primary food production environment: A scoping review","volume":"320","author":"Anedda","year":"2023","journal-title":"Environ. Pollut."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1271\/bbb.60024","article-title":"Characterization of copper-inducible promoters regulated by CpxA\/CpxR in Escherichia coli","volume":"70","author":"Yamamoto","year":"2006","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"616792","DOI":"10.3389\/fmicb.2020.616792","article-title":"Copper Ions Facilitate the Conjugative Transfer of SXT\/R391 Integrative and Conjugative Element Across Bacterial Genera","volume":"11","author":"Song","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"39721","DOI":"10.1074\/jbc.M112.383604","article-title":"A copper-responsive global repressor regulates expression of diverse membrane-associated transporters and bacterial drug resistance in Mycobacteria","volume":"287","author":"Rao","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1039\/C4MT00327F","article-title":"Copper tolerance and virulence in bacteria","volume":"7","author":"Ladomersky","year":"2015","journal-title":"Metallomics"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1039\/d0mt00140f","article-title":"Diversity, structure and regulation of microbial metallothionein: Metal resistance and possible applications in sequestration of toxic metals","volume":"12","author":"Chatterjee","year":"2020","journal-title":"Metallomics"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/5133\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:03:40Z","timestamp":1760126620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/5133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,30]]},"references-count":99,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["molecules28135133"],"URL":"https:\/\/doi.org\/10.3390\/molecules28135133","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,30]]}}}