{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:00:04Z","timestamp":1792803604929,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Research and Innovation (DRI)"},{"name":"University of Fort Hare","id":[{"id":"https:\/\/ror.org\/0184vwv17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"South Africa Medical Research Council (SAMRC)","id":[{"id":"https:\/\/ror.org\/05q60vz69","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: The need for innovative therapeutic strategies to enhance patient outcomes has increased due to the rise in bacterial co-infections associated with COVID-19. Methods: In this study, ten hybrid compounds were synthesized by combining two known pharmaceutical scaffolds to enhance antibacterial activity and overcome resistance mechanisms. The synthesized compounds were evaluated for their antibacterial activity against five Gram-negative and seven Gram-positive bacterial strains. In silico pharmacokinetic and drug-likeness properties of selected active compounds (12\u201316, 19, 21, and 23) were predicted using the SwissADME web tool. Results: Compounds 12\u201316, 19, 21, and 23 demonstrated significant antibacterial activity, with compound 16 (a ciprofloxacin-containing hybrid) exhibiting the most potent effect, showing a minimum inhibitory concentration (MIC) of 7.8125 \u00b5g\/mL against all tested bacterial strains. The in silico analysis revealed favorable pharmacokinetic profiles, drug-likeness, lipophilicity, and water solubility of most hybrid compounds. Discussion: The synthesized hybrid compounds exhibited enhanced antibacterial activity and desirable pharmacokinetic properties, particularly compound 16. These findings suggest the potential of these molecules in combating bacterial pathogens, especially those implicated in co-infections in COVID-19 infections. Conclusions: The study presents promising hybrid antibacterial agents with potential application as adjunct therapies for treating COVID-19-associated bacterial co-infections. Further investigation is needed, which may lead to effective treatments for managing secondary bacterial infections in viral disease contexts.<\/jats:p>","DOI":"10.3390\/antibiotics14060582","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T06:11:08Z","timestamp":1749190268000},"page":"582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Design and Synthesis of Hybrid Compounds for Potential Treatment of Bacterial Co-Infections: In Vitro Antibacterial and In Silico Studies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4875-1535","authenticated-orcid":false,"given":"Vuyolwethu","family":"Khwaza","sequence":"first","affiliation":[{"name":"Department of Chemistry, Alice Campus, University of Fort Hare, Alice 5700, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1240-3718","authenticated-orcid":false,"given":"Opeoluwa O.","family":"Oyedeji","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Alice Campus, University of Fort Hare, Alice 5700, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Morifi","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Division, School of Chemistry, University of Witwatersrand, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutshinyalo","family":"Nwamadi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Auckland Park Campus, University of Johannesburg, Johannesburg 2092, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry Youmbi","family":"Fonkui","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Doornfontein Campus, University of Johannesburg, Johannesburg 2028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek Tantoh","family":"Ndinteh","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, Doornfontein Campus, University of Johannesburg, Johannesburg 2028, 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 Chemistry, Alice Campus, University of Fort Hare, Alice 5700, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s15010-023-02063-2","article-title":"Community-acquired and hospital-acquired bacterial co-infections in patients hospitalized with COVID-19 or influenza: A retrospective cohort study","volume":"52","author":"Jorda","year":"2024","journal-title":"Infection"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e18041","DOI":"10.7717\/peerj.18041","article-title":"Bacterial co-infection in COVID-19: A call to stay vigilant","volume":"12","author":"Liu","year":"2024","journal-title":"PeerJ"},{"key":"ref_3","first-page":"e23687","article-title":"Opportunistic Infections in COVID-19: A Systematic Review and Meta-Analysis","volume":"14","author":"Kurra","year":"2022","journal-title":"Cureus"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.jiac.2022.05.006","article-title":"A case of Bacillus subtilis var. natto bacteremia caused by ingestion of natto during COVID-19 treatment in a maintenance hemodialysis patient with multiple myeloma","volume":"28","author":"Kato","year":"2022","journal-title":"J. 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