Blood–Brain Barrier Penetration of Novel 4-Trifluoromethyl-Coumarin Hybrids with Antibacterial Properties as Potential Brain Therapeutics in the Context of Spatially Diverse Healthcare Systems

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dc.contributor.authorKowalczyk, Paweł
dc.contributor.authorKoszelewski, Dominik
dc.contributor.authorMisztal, Tomasz
dc.contributor.authorSzlis, Michał
dc.contributor.authorMłotkowska, Patrycja
dc.contributor.authorGołębiewski, Marcin
dc.contributor.authorGłowacz, Krzysztof
dc.contributor.authorKocot, Malwina
dc.contributor.authorMarczyk, Michał
dc.contributor.authorWypych, Aleksandra
dc.contributor.authorKurylczyk, Apoloniusz
dc.contributor.authorKrajewska-Pędzik, Anna
dc.contributor.authorOstaszewski, Ryszard
dc.contributor.organizationKielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences
dc.contributor.organizationInstitute of Organic Chemistry, Polish Academy of Sciences
dc.contributor.organizationInstitute of Animal Sciences, Warsaw University of Life Sciences
dc.contributor.organizationFaculty of Management and Organization, Silesian University of Technology
dc.contributor.organizationDepartment of Data Science and Engineering, Silesian University of Technology
dc.contributor.organizationYale Cancer Center, Yale School of Medicine, New Haven, USA
dc.contributor.organizationCentre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University in Toruń
dc.contributor.organizationInstitute of Spatial Management and Socio-Economic Geography, University of Szczecin
dc.contributor.organizationInstitute of Physical Culture Sciences, University of Szczecin
dc.date.accessioned2025-10-24T14:46:41Z
dc.date.available2025-10-24T14:46:41Z
dc.date.issued2025
dc.date.submitted2025-10-24T12:59:44Zen
dc.description.abstractEffective treatment of central nervous system (CNS) infections remains a major challenge, as most therapeutic agents do not efficiently cross the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier (BCSFB). Coumarin derivatives are of particular interest due to their broad pharmacological activity, favorable safety profile, and potential to penetrate biological barriers. Eight novel coumarin-based peptidomimetics functionalized with trifluoromethyl or methyl scaffolds were synthesized and evaluated as antimicrobial agents with the ability to cross the blood–brain barrier. Antimicrobial activity of the investigated compounds was tested against Staphylococcus aureus and multiple Escherichia coli strains (K12, R2, R3, R4) using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Cytotoxicity was assessed in vitro in BALB/c-3T3 mouse fibroblasts and αT3-1 pituitary gonadotrope cells using the MTT assay. In vivo studies were performed in sheep to assess transfer of the compounds from blood to cerebrospinal fluid (CSF). All synthesized derivatives demonstrated antimicrobial activity and acceptable cytotoxicity, comparable to those of clinically used antibiotics. CF3-modified coumarin peptidomimetics show promise as antimicrobial agents with the potential to penetrate the BBB/BCSFB. These findings support further investigation of coumarin-based scaffolds as a platform for the development of novel therapeutics for CNS infections.en
dc.description.sponsorshipKielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences and the grant OPUS No. 2023/49/B/NZ7/02469 from Instite of Organic Chemistry Polish Academy of Sciences; Minister of Science under the “Regional Excellence Initiative”
dc.identifier.citationInt. J. Mol. Sci. 2025, 26(19), 9655 // https://doi.org/10.3390/ijms26199655
dc.identifier.doi10.3390/ijms26199655
dc.identifier.issn1661-6596
dc.identifier.issn1422-0067
dc.identifier.urihttps://open.icm.edu.pl/handle/123456789/26247
dc.language.isoen
dc.publisherMDPI
dc.relation.ispartofseries26; 19
dc.rightsUznanie autorstwa 4.0 Międzynarodoween
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceInternational Journal of Molecular Sciences
dc.subjectcoumarinsen
dc.subjectpeptidomimeticsen
dc.subjectiminesen
dc.subjectantimicrobial activityen
dc.subjectcerebrospinal fluiden
dc.subjectStaphylococcus aureusen
dc.subjectEscherichia colien
dc.titleBlood–Brain Barrier Penetration of Novel 4-Trifluoromethyl-Coumarin Hybrids with Antibacterial Properties as Potential Brain Therapeutics in the Context of Spatially Diverse Healthcare Systemsen
dc.typearticle
dc.type.versionpublishedVersion
person.identifier.orcidKoszelewski, Dominik [0000-0003-0968-3330]
person.identifier.orcidOstaszewski, Ryszard [0000-0002-3032-196X]
person.identifier.orcidMisztal, Tomasz [0000-0002-2556-4983]
person.identifier.orcidMłotkowska, Patrycja [0000-0002-5676-1373]
person.identifier.orcidGołębiewski, Marcin [0000-0003-0645-433X]
person.identifier.orcidMarczyk, Michał [0000-0003-2508-5736]
person.identifier.orcidWypych, Aleksandra [0000-0002-0555-8690]
person.identifier.orcidKurylczyk, Apoloniusz [0000-0002-6378-0580]
person.identifier.orcidKowalczyk, Paweł [0000-0003-4025-3750]
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