{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:51:39Z","timestamp":1791928299312,"version":"4.3.4"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Eight quinoline-based hydroxyimidazolium hybrids 7a\u2013h were prepared and evaluated in vitro against a panel of clinically important fungal and bacterial pathogens, including mycobacteria. Hybrid compounds 7c\u2013d showed remarkable antifungal activity against Cryptococcus neoformans with a minimum inhibitory concentration (MIC) value of 15.6 \u00b5g\/mL. Against other opportunistic fungi such as Candida spp. and Aspergillus spp., these hybrids showed MIC values of 62.5 \u00b5g\/mL. Regarding their antibacterial activity, all the synthetic hybrids demonstrated little inhibition of Gram-negative bacteria (MIC \u226550 \u00b5g\/mL), however, hybrid 7b displayed &gt;50% inhibition against Klebsiella pneumoniae at 20 \u00b5g\/mL and full inhibition at 50 \u00b5g\/mL. Moreover, this hybrid was shown to be a potent anti-staphylococcal molecule, with a MIC value of 2 \u00b5g\/mL (5 \u00b5M). In addition, hybrid 7h also demonstrated inhibition of Staphylococcus aureus at 20 \u00b5g\/mL (47 \u00b5M). Hybrids 7a and 7b were the most potent against Mycobacterium tuberculosis H37Rv with MIC values of 20 and 10 \u00b5g\/mL (46 and 24 \u00b5M), respectively. The 7b hybrid demonstrated high selectivity in killing S. aureus and M. tuberculosis H37Rv in comparison with mammalian cells (SI &gt;20), and thus it can be considered a hit molecule for mechanism of action studies and the exploration of related chemical space.<\/jats:p>","DOI":"10.3390\/antibiotics8040239","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T08:14:04Z","timestamp":1574928844000},"page":"239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Antimicrobial Activity of Quinoline-Based Hydroxyimidazolium Hybrids"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9662-9505","authenticated-orcid":false,"given":"Daniel","family":"Insuasty","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica y Biolog\u00eda, Universidad del Norte, Km 5 v\u00eda Puerto Colombia, Barranquilla 081007, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Vidal","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Biolog\u00eda, Universidad del Norte, Km 5 v\u00eda Puerto Colombia, Barranquilla 081007, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Bernal","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Biolog\u00eda, Universidad del Norte, Km 5 v\u00eda Puerto Colombia, Barranquilla 081007, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7503-1528","authenticated-orcid":false,"given":"Edgar","family":"Marquez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Biolog\u00eda, Universidad del Norte, Km 5 v\u00eda Puerto Colombia, Barranquilla 081007, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4120-9065","authenticated-orcid":false,"given":"Juan","family":"Guzman","sequence":"additional","affiliation":[{"name":"Institute for Insect Biotechnology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8371-3310","authenticated-orcid":false,"given":"Braulio","family":"Insuasty","sequence":"additional","affiliation":[{"name":"Research Group of Heterocyclic Compounds, Department of Chemistry, Universidad del Valle, A. A. Cali 25360, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9451-3063","authenticated-orcid":false,"given":"Jairo","family":"Quiroga","sequence":"additional","affiliation":[{"name":"Research Group of Heterocyclic Compounds, Department of Chemistry, Universidad del Valle, A. A. Cali 25360, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Svetaz","sequence":"additional","affiliation":[{"name":"\u00c1rea Farmacognosia, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-5500","authenticated-orcid":false,"given":"Susana","family":"Zacchino","sequence":"additional","affiliation":[{"name":"\u00c1rea Farmacognosia, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Puerto","sequence":"additional","affiliation":[{"name":"Laboratorio de Micobacterias, Instituto Nacional de Salud, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Abonia","sequence":"additional","affiliation":[{"name":"Research Group of Heterocyclic Compounds, Department of Chemistry, Universidad del Valle, A. A. Cali 25360, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/nrmicro2319","article-title":"Antibiotic resistance and its cost: is it possible to reverse resistance?","volume":"8","author":"Andersson","year":"2010","journal-title":"Nat. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/nyas.13739","article-title":"New pathogens, new tricks: Emerging, drug-resistant fungal pathogens and future prospects for antifungal therapeutics","volume":"1435","author":"Shapiro","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8720","DOI":"10.1021\/acsomega.8b02481","article-title":"Design, synthesis, antimicrobial evaluation, and molecular modeling studies of novel indolinedione\u2013coumarin molecular hybrids","volume":"4","author":"Bhagat","year":"2019","journal-title":"ACS Omega"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.2174\/1389557516666160609075620","article-title":"Hybrid bioactive heterocycles as potential antimicrobial agents: a review","volume":"16","author":"Desai","year":"2016","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejmech.2019.04.033","article-title":"1,2,4-Triazole-quinoline\/quinolone hybrids as potential anti-bacterial agents","volume":"174","author":"Zhang","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4103\/ijmr.IJMR_2079_17","article-title":"Efflux pump inhibitors for bacterial pathogens: From bench to bedside","volume":"149","author":"Sharma","year":"2019","journal-title":"Indian J. Med. Res."},{"key":"ref_7","unstructured":"World Health Organization (2015). Guidelines for the Treatment of Malaria, World Health Organization."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4874","DOI":"10.1021\/jm501881c","article-title":"Origins of the quinolone class of antibacterials: An expanded \u201cdiscovery story\u201d","volume":"58","author":"Bisacchi","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1056\/NEJM199102073240606","article-title":"Fluoroquinolone antimicrobial agents","volume":"324","author":"Hooper","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms4369","article-title":"Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism","volume":"5","author":"Koul","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"087015","DOI":"10.1289\/EHP1404","article-title":"In vitro evaluation of mitochondrial function and estrogen signaling in cell lines exposed to the antiseptic cetylpyridinium chloride","volume":"125","author":"Datta","year":"2017","journal-title":"Environ. Health Perspect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"598","DOI":"10.3923\/pjbs.2007.598.601","article-title":"The antimicrobial effect of benzalkonium chloride on some pathogenic microbes observed on fibers of acrylic carpet","volume":"10","author":"Khajavi","year":"2007","journal-title":"Pakistan J. Biol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"424","DOI":"10.2165\/00003495-197509060-00003","article-title":"Clotrimazole: A review of its antifungal activity and therapeutic efficacy","volume":"9","author":"Sawyer","year":"1975","journal-title":"Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0002-9343(83)90508-9","article-title":"The antifungal activity of ketoconazole","volume":"74","author":"Cutsem","year":"1983","journal-title":"Am. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"406","DOI":"10.2165\/00003495-197509060-00002","article-title":"Miconazole: A review of its antifungal activity and therapeutic efficacy","volume":"9","author":"Sawyer","year":"1975","journal-title":"Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1021\/np030031i","article-title":"Imidazole alkaloids from lepidium meyenii","volume":"66","author":"Cui","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ejmech.2013.09.029","article-title":"Toward new classes of potent antibiotics: Synthesis and antimicrobial activity of novel metallosaldach\u2013imidazolium salts","volume":"75","author":"Elshaarawy","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9055","DOI":"10.1039\/c3cs60169b","article-title":"Imidazolium salts and their polymeric materials for biological applications","volume":"42","author":"Riduan","year":"2013","journal-title":"Chem. Soc. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.bbrc.2015.10.015","article-title":"Anti-tumor activity and cytotoxicity in vitro of novel 4, 5-dialkylimidazolium surfactants","volume":"467","author":"Wang","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4395","DOI":"10.1016\/j.tetlet.2014.05.094","article-title":"Novel quinoline\u2013imidazolium adducts via the reaction of 2-oxoquinoline-3-carbaldehyde and quinoline-3-carbaldehydes with 1-butyl-3-methylimidazolium chloride [BMIM][Cl]","volume":"55","author":"Laali","year":"2014","journal-title":"Tetrahedron Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"539","DOI":"10.3987\/REV-92-SR4","article-title":"The synthesis of pyridines, quinolines and other related systems by the Vilsmeier and the reverse Vilsmeier method","volume":"35","year":"1993","journal-title":"Heterocycles"},{"key":"ref_22","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2008). Document M27A3. Reference Method For Broth Dilution Antifungal Susceptibility Testing of Yeasts, CLSI."},{"key":"ref_23","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2008). Document M38A2. Reference Method For Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi, CLSI."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s12039-013-0371-4","article-title":"Synthesis, characterization and antimicrobial screening of hybrid molecules containing quinoline, pyrimidine and morpholine analogues","volume":"125","author":"Desai","year":"2013","journal-title":"J. Chem. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6871","DOI":"10.1016\/j.bmcl.2012.09.039","article-title":"Synthesis and characterization of some new quinoline based derivatives endowed with broad spectrum antimicrobial potency","volume":"22","author":"Desai","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1016\/j.bmcl.2014.02.044","article-title":"Synthesis and evaluation of new diaryl ether and quinoline hybrids as potential antiplasmodial and antimicrobial agents","volume":"24","author":"Mishra","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jfluchem.2016.01.011","article-title":"Synthesis and antitubercular and antibacterial activity of some active fluorine containing quinoline\u2013pyrazole hybrid derivatives","volume":"183","author":"Nayak","year":"2016","journal-title":"J. Fluor. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.biopha.2014.10.007","article-title":"Quinoline: A promising antitubercular target","volume":"68","author":"Keri","year":"2014","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/jm4014778","article-title":"Quinoline\u2013Pyrimidine Hybrids: Synthesis, Antiplasmodial Activity, SAR, and Mode of Action Studies","volume":"57","author":"Singh","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.1021\/jm200149e","article-title":"Enone\u2013 and Chalcone\u2013Chloroquinoline Hybrid Analogues: In Silico Guided Design, Synthesis, Antiplasmodial Activity, in Vitro Metabolism, and Mechanistic Studies","volume":"54","author":"Guantai","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.ejmech.2014.10.068","article-title":"Identification of quinoline-chalcone hybrids as potential antiulcer agents","volume":"89","author":"Sashidhara","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mantoani, S., Chierrito, T., Vilela, A., Cardoso, C., Mart\u00ednez, A., and Carvalho, I. (2016). Novel Triazole-Quinoline Derivatives as Selective Dual Binding Site Acetylcholinesterase Inhibitors. Molecules, 21.","DOI":"10.3390\/molecules21020193"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5365","DOI":"10.1021\/jm900859q","article-title":"Pyrano[3,2-c]quinoline\u22126-Chlorotacrine Hybrids as a Novel Family of Acetylcholinesterase- and \u03b2-Amyloid-Directed Anti-Alzheimer Compounds","volume":"52","author":"Camps","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1093\/jac\/dkq313","article-title":"Anti-tubercular screening of natural products from Colombian plants: 3-methoxynordomesticine, an inhibitor of MurE ligase of Mycobacterium tuberculosis","volume":"65","author":"Guzman","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gillespie, S.H., and McHugh, T.D. (2010). Rapid Methods for Testing Inhibitors of Mycobacterial Growth. Antibiotic Resistance Protocols, Humana Press. [2nd ed.]. Methods in Molecular Biology.","DOI":"10.1007\/978-1-60327-279-7"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cree, I.A. (2011). Cell Sensitivity Assays: The MTT Assay. Cancer Cell Culture: Methods and Protocols, Humana Press. Methods in Molecular Biology.","DOI":"10.1007\/978-1-61779-080-5"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/8\/4\/239\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:38:12Z","timestamp":1760189892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/8\/4\/239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,28]]},"references-count":36,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["antibiotics8040239"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics8040239","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,28]]}}}