{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T04:40:04Z","timestamp":1777092004261,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre (NCN, Poland)","award":["UMO-2016\/21\/B\/ST5\/00101."],"award-info":[{"award-number":["UMO-2016\/21\/B\/ST5\/00101."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Infections of Candida spp. etiology are frequently treated with azole drugs. Among azoles, the most widely used in the clinical scenario remains fluconazole (FLC). Promising results in treatment of dangerous, systemic Candida infections demonstrate the advantages of combined therapies carried out with combinations of at least two different antifungal agents. Here, we report five conjugates composed of covalently linked FLC and cell penetrating or antimicrobial peptide: TP10-7-NH2, TP10-NH2, LFcinB(2-11)-NH2, LFcinB[Nle1,11]-NH2, and HLopt2-NH2, with aspects of design, chemical synthesis and their biological activities. Two of these compounds, namely FLCpOH-TP10-NH2 and FLCpOH-TP10-7-NH2, exhibit high activity against reference strains and fluconazole-resistant clinical isolates of C. albicans, including strains overproducing drug transporters. Moreover, both of them demonstrate higher fungicidal effects compared to fluconazole. Analysis performed with fluorescence and scanning electron microscopy as well as flow cytometry indicated the cell membrane as a molecular target of synthesized conjugates. An important advantage of FLCpOH-TP10-NH2 and FLCpOH-TP10-7-NH2 is their low cytotoxicity. The IC90 value for the human cells after 72 h treatment was comparable to the MIC50 value after 24 h treatment for most strains of C. albicans. In reported conjugates, FLC was linked to the peptide by its hydroxyl group. It is worth noting that conjugation of FLC by the nitrogen atom of the triazole ring led to practically inactive compounds. Two compounds produced by us and reported herein appear to be potential candidates for novel antifungal agents.<\/jats:p>","DOI":"10.3390\/pharmaceutics14040693","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T22:08:06Z","timestamp":1648073286000},"page":"693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["New Peptide Based Fluconazole Conjugates with Expanded Molecular Targets"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8314-0775","authenticated-orcid":false,"given":"Wioletta","family":"Brankiewicz","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gda\u0144sk University of Technology, Narutowicza 11\/12, 80-233 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Oko\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, 80-308 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Serbakowska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gda\u0144sk University of Technology, Narutowicza 11\/12, 80-233 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6374-3635","authenticated-orcid":false,"given":"Jan","family":"Lica","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, 80-308 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marek","family":"Drab","sequence":"additional","affiliation":[{"name":"Unit of Nanostructural Bio-Interactions, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla-Street, 53-114 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7576-0248","authenticated-orcid":false,"given":"Natalia","family":"Ptaszy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, 80-308 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1665-3180","authenticated-orcid":false,"given":"Anna","family":"\u0141\u0119gowska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, 80-308 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-700X","authenticated-orcid":false,"given":"Krzysztof","family":"Rolka","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, 80-308 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8291-5148","authenticated-orcid":false,"given":"Piotr","family":"Szweda","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gda\u0144sk University of Technology, Narutowicza 11\/12, 80-233 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. 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