{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:16:45Z","timestamp":1791483405844,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009543","name":"Pontificia Universidad Javeriana","doi-asserted-by":"publisher","award":["20274"],"award-info":[{"award-number":["20274"]}],"id":[{"id":"10.13039\/501100009543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009543","name":"Pontificia Universidad Javeriana","doi-asserted-by":"publisher","award":["12150370101103"],"award-info":[{"award-number":["12150370101103"]}],"id":[{"id":"10.13039\/501100009543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009543","name":"Pontificia Universidad Javeriana","doi-asserted-by":"publisher","award":["2023215"],"award-info":[{"award-number":["2023215"]}],"id":[{"id":"10.13039\/501100009543","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MINCIENCIAS Colombia","award":["20274"],"award-info":[{"award-number":["20274"]}]},{"name":"MINCIENCIAS Colombia","award":["12150370101103"],"award-info":[{"award-number":["12150370101103"]}]},{"name":"MINCIENCIAS Colombia","award":["2023215"],"award-info":[{"award-number":["2023215"]}]},{"name":"785 National Ph.D. Program","award":["20274"],"award-info":[{"award-number":["20274"]}]},{"name":"785 National Ph.D. Program","award":["12150370101103"],"award-info":[{"award-number":["12150370101103"]}]},{"name":"785 National Ph.D. Program","award":["2023215"],"award-info":[{"award-number":["2023215"]}]},{"name":"Universidad Antonio Nari\u00f1o","award":["20274"],"award-info":[{"award-number":["20274"]}]},{"name":"Universidad Antonio Nari\u00f1o","award":["12150370101103"],"award-info":[{"award-number":["12150370101103"]}]},{"name":"Universidad Antonio Nari\u00f1o","award":["2023215"],"award-info":[{"award-number":["2023215"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study reports the synthesis, characterization, and antifungal evaluation of a series of pyridoxal and salicylaldehyde derivatives, using synthetic methodologies such as radical cyclizations and click chemistry. Compounds 6a and 6b, featuring a fused dihydrobenzoxepine-pyridine scaffold, demonstrated effective fungicidal activity with MIC values of 19 \u00b5g\/mL against Cryptococcus neoformans 2807. Similarly, compound 6b exhibited notable activity with a MIC of 75 \u00b5g\/mL against Candida auris PUJ-HUSI 537. Both compounds outperformed fluconazole (FLC) in these strains. In silico ADMET profiling revealed favorable pharmacokinetic properties, including blood\u2013brain barrier penetration and drug-likeness parameters consistent with Lipinski\u2019s rule of five. Cytotoxicity assays on human fibroblasts confirmed the low toxicity of compound 6a at the tested concentrations. These results highlight the potential of the fused dihydrobenzoxepine-pyridine scaffold as a promising antifungal candidate for further investigations.<\/jats:p>","DOI":"10.3390\/molecules30051165","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T03:18:22Z","timestamp":1741144702000},"page":"1165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pyridoxal and Salicylaldehyde Derivatives: Synthesis, Characterization, and Antifungal Potential Against Opportunistic Yeast Pathogens"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8960-2718","authenticated-orcid":false,"given":"Jairo","family":"Camacho","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 No. 40-62, Bogot\u00e1 110231, Colombia"},{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad Antonio Nari\u00f1o, Cra. 3 Este No. 47 A-15, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3447-8833","authenticated-orcid":false,"given":"Carlos A.","family":"Bejarano","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad Antonio Nari\u00f1o, Cra. 3 Este No. 47 A-15, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8447-307X","authenticated-orcid":false,"given":"John E.","family":"Diaz","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad Antonio Nari\u00f1o, Cra. 3 Este No. 47 A-15, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4788-8150","authenticated-orcid":false,"given":"Yerly","family":"Vargas-Casanova","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 No. 40-62, Bogot\u00e1 110231, Colombia"},{"name":"Facultad de Ingenier\u00eda y Ciencias B\u00e1sicas, Instituto Tecnol\u00f3gico del Putumayo, Mocoa 860001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8772-9261","authenticated-orcid":false,"given":"Silvia Katherine","family":"Carvajal","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 No. 40-62, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9804-2254","authenticated-orcid":false,"given":"Valentina","family":"Diaz Santoyo","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 No. 40-62, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1302-5429","authenticated-orcid":false,"given":"Claudia M.","family":"Parra-Giraldo","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 No. 40-62, Bogot\u00e1 110231, Colombia"},{"name":"Departamento de Biomedicina, Facultad de Ciencias de la Salud y Biociencias, Universidad Europea de Madrid, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9413-9502","authenticated-orcid":false,"given":"Alix E.","family":"Loaiza","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 No. 40-62, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.15698\/mic2020.06.718","article-title":"Fungal infections in humans: The silent crisis","volume":"7","author":"Kainz","year":"2020","journal-title":"Microb. Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e200430","DOI":"10.1590\/0074-02760200430","article-title":"Invasive fungal disease in humans: Are we aware of the real impact?","volume":"115","author":"Firacative","year":"2020","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nrmicro2711","article-title":"Candida albicans morphogenesis and host defence: Discriminating invasion from colonization","volume":"10","author":"Gow","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ijid.2018.01.034","article-title":"First report of sporadic cases of Candida auris in Colombia","volume":"69","author":"Valderrama","year":"2018","journal-title":"Int. J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s12281-019-00340-y","article-title":"Cryptococcal Pathogenicity and Morphogenesis","volume":"13","year":"2019","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1093\/jac\/dkad139","article-title":"Invasive candidiasis: Current clinical challenges and unmet needs in adult populations","volume":"78","author":"Soriano","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1080\/14756366.2022.2050224","article-title":"Echinocandins\u2013structure, mechanism of action and use in antifungal therapy","volume":"37","author":"Chmielewska","year":"2022","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Shafiei, M., Peyton, L., Hashemzadeh, M., and Foroumadi, A. (2020). History of the development of antifungal azoles: A review on structures, SAR, and mechanism of action. Bioorg. Chem., 104.","DOI":"10.1016\/j.bioorg.2020.104240"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Costa-de-oliveira, S., and Rodrigues, A.G. (2020). Candida albicans antifungal resistance and tolerance in bloodstream infections: The triad yeast-host-antifungal. Microorganisms, 8.","DOI":"10.3390\/microorganisms8020154"},{"key":"ref_10","first-page":"145","article-title":"Mecanismos de resistencia antif\u00fangica de los azoles en Candida albicans. Una revisi\u00f3n","volume":"27","year":"2016","journal-title":"Rev. Biom\u00e9d."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40249-023-01073-4","article-title":"Cryptococcus neoformans, a global threat to human health","volume":"12","author":"Zhao","year":"2023","journal-title":"Infect. Dis. Poverty"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Spadari, C.D.C., Wirth, F., Lopes, L.B., and Ishida, K. (2020). New approaches for cryptococcosis treatment. Microorganisms, 8.","DOI":"10.3390\/microorganisms8040613"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1002\/jhet.3874","article-title":"Synthesis and antifungal activity of novel 1,2,4-triazole derivatives containing an amide moiety","volume":"57","author":"Wu","year":"2020","journal-title":"J. Heterocycl. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"133901","DOI":"10.1016\/j.molstruc.2022.133901","article-title":"Synthesis and antifungal activity evaluation of novel pyridine derivatives as potential succinate dehydrogenase inhibitors","volume":"1270","author":"Jiang","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ejmech.2019.03.023","article-title":"Tetrazole hybrids and their antifungal activities","volume":"170","author":"Wang","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","first-page":"294","article-title":"Synthesis and in vitro assessment of antifungal activity of oximes, oxime ethers and isoxazoles","volume":"16","author":"Loaiza","year":"2011","journal-title":"Univ. Sci."},{"key":"ref_17","first-page":"30","article-title":"Design, Synthesis, Characterization and Biological Activity of Novel Thieno[2,3-d]pyrimidine Derivatives","volume":"5","author":"Prabhakar","year":"2017","journal-title":"Indian J. Adv. Chem. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.3390\/md10122691","article-title":"A new dibenz[b,e]oxepine derivative, 1-hydroxy-10-methoxy-dibenz[b,e] oxepin-6,11-dione, from a marine-derived fungus, Beauveria bassiana TPU942","volume":"10","author":"Yamazaki","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cardoso, J., Nakayama, D.G., Sousa, E., and Pinto, E. (2020). Marine-Derived Compounds and Prospects for Their Antifungal Application. Molecules, 25.","DOI":"10.3390\/molecules25245856"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7181","DOI":"10.1016\/S0040-4020(01)00640-8","article-title":"Synthesis of the antifungal 1-benzoxepin pterulone","volume":"57","author":"Kahnberg","year":"2001","journal-title":"Tetrahedron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1021\/acs.jnatprod.0c00587","article-title":"Synthesis and Antifungal Activity of Chromones and Benzoxepines from the Leaves of Ptaeroxylon obliquum","volume":"83","author":"Malefo","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vlad, I.M., Nuta, D.C., Chirita, C., Caproiu, M.T., Draghici, C., Dumitrascu, F., Bleotu, C., Avram, S., Udrea, A.M., and Missir, A.V. (2020). In Silico and In Vitro Experimental Studies of New Dibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents. Molecules, 25.","DOI":"10.3390\/molecules25020321"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1248\/cpb.39.2564","article-title":"Synthesis and Biological Activity of 11-(4-(Cinnamyl)-1-piperazinyl)-6, 11-dihydrodibenzo(b,e)oxepin Derivatives, Potential Agents for the Treatment of Cerebrovascular Disorders","volume":"39","author":"Kurokawa","year":"1992","journal-title":"Chem. Pharm. Bull."},{"key":"ref_24","unstructured":"Scoccia, J., Castro, M.J., Faraoni, M.B., Bouzat, C., Mart\u00edn, V.S., and Gerbino, D.C. (2016, January 1\u201330). Efficient synthesis and biological evaluation of dibenzo[b,e]oxepin-11(6H)-ones as potential anthelmintic agents. Proceedings of the 20th International Electronic Conference on Synthetic Organic Chemistry, Bah\u00eda Blanca, Argentina."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ga\u0161parov\u00e1, R. (2022). Natural Compounds with Oxepinochromene Scaffold. Structure, Source, Biological Activity and Synthesis. Chem. Biodivers., 19.","DOI":"10.1002\/cbdv.202200507"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6761","DOI":"10.1016\/j.tetlet.2012.09.129","article-title":"Click chemistry inspired structural modification of azole antifungal agents to synthesize novel \u2018drug like\u2019 molecules","volume":"53","author":"Pericherla","year":"2012","journal-title":"Tetrahedron Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7884316","DOI":"10.1155\/2022\/7884316","article-title":"A Recent Overview of 1,2,3-Triazole-Containing Hybrids as Novel Antifungal Agents: Focusing on Synthesis, Mechanism of Action, and Structure-Activity Relationship (SAR)","volume":"2022","author":"Marzi","year":"2022","journal-title":"J. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6756","DOI":"10.1002\/chem.201000438","article-title":"Microwave-assisted, aqueous wittig reactions: Organic-solvent- And protecting-group-free chemoselective synthesis of functionalized alkenes","volume":"16","author":"McNulty","year":"2010","journal-title":"Chemistry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e202301148","DOI":"10.1002\/ejoc.202301148","article-title":"Study of the Mechanism of 7-exo-trig Cyclizations of Aryl, Vinyl, and Alkyl Radicals on Oxime Ethers","volume":"27","author":"Bejarano","year":"2024","journal-title":"Eur. J. Org. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1039\/D2OB00387B","article-title":"Experimental and theoretical study of the mechanism and rate constants of the sequential 5-exo-trig spirocyclization involving vinyl, aryl and N-alkoxyaminyl radicals","volume":"20","author":"Bejarano","year":"2022","journal-title":"Org. Biomol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1021\/ja0471525","article-title":"Copper(I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates","volume":"127","author":"Himo","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/aoc.1378","article-title":"Antimicrobial activity of organotin(IV) compounds: A review","volume":"22","author":"Baul","year":"2008","journal-title":"Appl. Organomet. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1177\/1091581814530437","article-title":"Cytotoxic effects of a novel thialo benzene derivative 2,4-Dithiophenoxy-1- iodo-4-bromobenzene (C18H12S2IBr) in L929 cells","volume":"33","year":"2014","journal-title":"Int. J. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7236","DOI":"10.1002\/slct.202001329","article-title":"Palindromic Peptide LfcinB (21-25)Pal Exhibited Antifungal Activity against Multidrug-Resistant Candida","volume":"5","author":"Poveda","year":"2020","journal-title":"ChemistrySelect"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Casanova, Y.V., Guerra, J.A.R., P\u00e9rez, Y.A.U., Castro, A.L.L., Reina, G.A., Casta\u00f1eda, J.E.G., and Monroy, Z.J.R. (2017). Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines. Molecules, 22.","DOI":"10.3390\/molecules22101641"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1039\/p19940003499","article-title":"Intramolecular Addition of Vinyl and Aryl Radicals to Oxime Ethers in the Synthesis of Five-, Six-and Seven-membered Ring Systems","volume":"23","author":"Booth","year":"1994","journal-title":"J. Chem. Soc. Perkin Trans."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/5\/1165\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:47:20Z","timestamp":1760028440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/5\/1165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":37,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["molecules30051165"],"URL":"https:\/\/doi.org\/10.3390\/molecules30051165","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,5]]}}}