{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:02:57Z","timestamp":1793743377227,"version":"4.6.1"},"reference-count":63,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"South African Medical Research Council (SAMRC)","id":[{"id":"https:\/\/ror.org\/05q60vz69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research Foundation (NRF)"},{"name":"Govan Mbeki Research and Development Council (GMRDC) at the University of Fort Hare, South Africa","id":[{"id":"https:\/\/ror.org\/0184vwv17","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The alarming increase in antimicrobial resistance has intensified the search for novel therapeutic agents capable of combating resistant microbial strains. Copper complexes have emerged as promising antimicrobial agents due to their intrinsic redox activity, ability to disrupt microbial membranes, and interactions with vital biomolecules such as DNA and proteins. This review critically evaluates the antimicrobial potential of copper complexes reported between 2018 and 2025, emphasizing their structural diversity, mechanisms of action, and biological performance against a wide range of bacterial and fungal pathogens. Key findings reveal that Schiff base copper complexes, amino acid derivatives, heterocyclic ligands, and mixed-ligand systems exhibit potent antimicrobial activities, often surpassing standard antibiotics. Mechanistically, copper complexes induce reactive oxygen species (ROS) generation, inhibit enzyme function, cause DNA cleavage, and compromise cell membrane integrity. Furthermore, structure\u2013activity relationship (SAR) analyses indicate that ligand type, coordination geometry, and lipophilicity significantly influence antimicrobial efficacy. Overall, the reviewed studies support the development of copper-based compounds as viable candidates for antimicrobial drug development. This review also identifies current challenges and gaps in knowledge, such as limited in vivo studies and toxicity assessments, which must be addressed to advance these compounds toward clinical application.<\/jats:p>","DOI":"10.3390\/antibiotics14050516","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T05:11:57Z","timestamp":1747372317000},"page":"516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["The Antimicrobial Efficacy of Copper Complexes: A Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3955-1083","authenticated-orcid":false,"given":"Kwanele","family":"Ngece","sequence":"first","affiliation":[{"name":"Department of Chemical and Earth Sciences, University of Fort Hare, Alice 5700, Eastern Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4875-1535","authenticated-orcid":false,"given":"Vuyolwethu","family":"Khwaza","sequence":"additional","affiliation":[{"name":"Department of Chemical and Earth Sciences, University of Fort Hare, Alice 5700, Eastern Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athandwa M.","family":"Paca","sequence":"additional","affiliation":[{"name":"Department of Chemical and Earth Sciences, University of Fort Hare, Alice 5700, Eastern Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1157-7481","authenticated-orcid":false,"given":"Blessing A.","family":"Aderibigbe","sequence":"additional","affiliation":[{"name":"Department of Chemical and Earth Sciences, University of Fort Hare, Alice 5700, Eastern Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Aissaoui, Y. 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