No Cover Image

Journal article 283 views 138 downloads

Design and Synthesis of Ketoconazole Derivatives as Innovative Anti‐Infective Agents

Gioele Renzi Orcid Logo, Andrea Angeli Orcid Logo, Silvia Selleri, Costanza Spadini Orcid Logo, Nicolo’ Mezzasalma, Marcus Hull, Steven Kelly, Clemente Capasso, Clotilde S. Cabassi Orcid Logo, Fabrizio Carta Orcid Logo, Claudiu T. Supuran Orcid Logo

Archiv der Pharmazie, Volume: 358, Issue: 7, Start page: e70062

Swansea University Authors: Marcus Hull, Steven Kelly

  • ardp.70062.pdf

    PDF | Version of Record

    © 2025 The Author(s). Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft. This is an open access article under the terms of the Creative Commons Attribution License (CC BY).

    Download (2.6MB)

Check full text

DOI (Published version): 10.1002/ardp.70062

Abstract

A novel series of compounds was designed and synthesized by combining the distal piperazine nitrogen of the antifungal ketoconazole (KTZ) with primary arylsulfonamides. The aim of this study is to present the basis for a new generation of Malassezia antifungal agents able to inhibit the enzyme lanos...

Full description

Published in: Archiv der Pharmazie
ISSN: 0365-6233 1521-4184
Published: Wiley 2025
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa70049
first_indexed 2025-07-29T11:47:06Z
last_indexed 2025-07-30T10:13:53Z
id cronfa70049
recordtype SURis
fullrecord <?xml version="1.0"?><rfc1807><datestamp>2025-07-29T12:48:29.3481430</datestamp><bib-version>v2</bib-version><id>70049</id><entry>2025-07-29</entry><title>Design and Synthesis of Ketoconazole Derivatives as Innovative Anti&#x2010;Infective Agents</title><swanseaauthors><author><sid>515e226de019435de4d1f871a82906dc</sid><ORCID/><firstname>Marcus</firstname><surname>Hull</surname><name>Marcus Hull</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>b17cebaf09b4d737b9378a3581e3de93</sid><firstname>Steven</firstname><surname>Kelly</surname><name>Steven Kelly</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2025-07-29</date><deptcode>MEDS</deptcode><abstract>A novel series of compounds was designed and synthesized by combining the distal piperazine nitrogen of the antifungal ketoconazole (KTZ) with primary arylsulfonamides. The aim of this study is to present the basis for a new generation of Malassezia antifungal agents able to inhibit the enzyme lanosterol&#x2010;14&#x3B1;&#x2010;demethylase (CYP51; EC 1.14.13.70) as well as a newly emergent therapeutic target: carbonic anhydrases (CAs; EC 4.2.1.1). The final compounds showed effective interactions with the intended targets in vitro, as well as KTZ comparable minimum inhibitory concentrations on yeast strains of the Malassezia genus: Malassezia furfur ATCC 14521; Malassezia globosa ATCC MYA 4612; and Malassezia pachydermatis DSM 6172. Overall, the data obtained account for the reported compounds as promising antifungal candidates with high safety profiles for the management of fungal infections.</abstract><type>Journal Article</type><journal>Archiv der Pharmazie</journal><volume>358</volume><journalNumber>7</journalNumber><paginationStart>e70062</paginationStart><paginationEnd/><publisher>Wiley</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0365-6233</issnPrint><issnElectronic>1521-4184</issnElectronic><keywords>14&#x3B1;-demethylase, antifungals, carbonic anhydrases, fungi, Malassezia</keywords><publishedDay>29</publishedDay><publishedMonth>7</publishedMonth><publishedYear>2025</publishedYear><publishedDate>2025-07-29</publishedDate><doi>10.1002/ardp.70062</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>F.C. was grateful to Ente Cassa di Risparmio di Firenze for partially supporting this work. Project title &#x201C;Progettazione e Sintesi di Nuovi Agenti per la Cura e la Profilassi di Infezioni Batteriche Resistenti&#x201D;. CRF 2018.1001. Open access publishing facilitated by Universita degli Studi di Firenze, as part of the Wiley - CRUI-CARE agreement.</funders><projectreference/><lastEdited>2025-07-29T12:48:29.3481430</lastEdited><Created>2025-07-29T12:40:41.3396970</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Gioele</firstname><surname>Renzi</surname><orcid>0009-0008-9109-030X</orcid><order>1</order></author><author><firstname>Andrea</firstname><surname>Angeli</surname><orcid>0000-0002-1470-7192</orcid><order>2</order></author><author><firstname>Silvia</firstname><surname>Selleri</surname><order>3</order></author><author><firstname>Costanza</firstname><surname>Spadini</surname><orcid>0000-0003-0211-5293</orcid><order>4</order></author><author><firstname>Nicolo&#x2019;</firstname><surname>Mezzasalma</surname><order>5</order></author><author><firstname>Marcus</firstname><surname>Hull</surname><orcid/><order>6</order></author><author><firstname>Steven</firstname><surname>Kelly</surname><order>7</order></author><author><firstname>Clemente</firstname><surname>Capasso</surname><order>8</order></author><author><firstname>Clotilde S.</firstname><surname>Cabassi</surname><orcid>0000-0002-1936-9858</orcid><order>9</order></author><author><firstname>Fabrizio</firstname><surname>Carta</surname><orcid>0000-0002-1141-6146</orcid><order>10</order></author><author><firstname>Claudiu T.</firstname><surname>Supuran</surname><orcid>0000-0003-4262-0323</orcid><order>11</order></author></authors><documents><document><filename>70049__34855__27ea40edcdf24b8c8277dea0acd36b16.pdf</filename><originalFilename>ardp.70062.pdf</originalFilename><uploaded>2025-07-29T12:40:41.1651028</uploaded><type>Output</type><contentLength>2726538</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>&#xA9; 2025 The Author(s). Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft. This is an open access article under the terms of the Creative Commons Attribution License (CC BY).</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language><licence>http://creativecommons.org/licenses/by/4.0/</licence></document></documents><OutputDurs/></rfc1807>
spelling 2025-07-29T12:48:29.3481430 v2 70049 2025-07-29 Design and Synthesis of Ketoconazole Derivatives as Innovative Anti‐Infective Agents 515e226de019435de4d1f871a82906dc Marcus Hull Marcus Hull true false b17cebaf09b4d737b9378a3581e3de93 Steven Kelly Steven Kelly true false 2025-07-29 MEDS A novel series of compounds was designed and synthesized by combining the distal piperazine nitrogen of the antifungal ketoconazole (KTZ) with primary arylsulfonamides. The aim of this study is to present the basis for a new generation of Malassezia antifungal agents able to inhibit the enzyme lanosterol‐14α‐demethylase (CYP51; EC 1.14.13.70) as well as a newly emergent therapeutic target: carbonic anhydrases (CAs; EC 4.2.1.1). The final compounds showed effective interactions with the intended targets in vitro, as well as KTZ comparable minimum inhibitory concentrations on yeast strains of the Malassezia genus: Malassezia furfur ATCC 14521; Malassezia globosa ATCC MYA 4612; and Malassezia pachydermatis DSM 6172. Overall, the data obtained account for the reported compounds as promising antifungal candidates with high safety profiles for the management of fungal infections. Journal Article Archiv der Pharmazie 358 7 e70062 Wiley 0365-6233 1521-4184 14α-demethylase, antifungals, carbonic anhydrases, fungi, Malassezia 29 7 2025 2025-07-29 10.1002/ardp.70062 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee F.C. was grateful to Ente Cassa di Risparmio di Firenze for partially supporting this work. Project title “Progettazione e Sintesi di Nuovi Agenti per la Cura e la Profilassi di Infezioni Batteriche Resistenti”. CRF 2018.1001. Open access publishing facilitated by Universita degli Studi di Firenze, as part of the Wiley - CRUI-CARE agreement. 2025-07-29T12:48:29.3481430 2025-07-29T12:40:41.3396970 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Gioele Renzi 0009-0008-9109-030X 1 Andrea Angeli 0000-0002-1470-7192 2 Silvia Selleri 3 Costanza Spadini 0000-0003-0211-5293 4 Nicolo’ Mezzasalma 5 Marcus Hull 6 Steven Kelly 7 Clemente Capasso 8 Clotilde S. Cabassi 0000-0002-1936-9858 9 Fabrizio Carta 0000-0002-1141-6146 10 Claudiu T. Supuran 0000-0003-4262-0323 11 70049__34855__27ea40edcdf24b8c8277dea0acd36b16.pdf ardp.70062.pdf 2025-07-29T12:40:41.1651028 Output 2726538 application/pdf Version of Record true © 2025 The Author(s). Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft. This is an open access article under the terms of the Creative Commons Attribution License (CC BY). true eng http://creativecommons.org/licenses/by/4.0/
title Design and Synthesis of Ketoconazole Derivatives as Innovative Anti‐Infective Agents
spellingShingle Design and Synthesis of Ketoconazole Derivatives as Innovative Anti‐Infective Agents
Marcus Hull
Steven Kelly
title_short Design and Synthesis of Ketoconazole Derivatives as Innovative Anti‐Infective Agents
title_full Design and Synthesis of Ketoconazole Derivatives as Innovative Anti‐Infective Agents
title_fullStr Design and Synthesis of Ketoconazole Derivatives as Innovative Anti‐Infective Agents
title_full_unstemmed Design and Synthesis of Ketoconazole Derivatives as Innovative Anti‐Infective Agents
title_sort Design and Synthesis of Ketoconazole Derivatives as Innovative Anti‐Infective Agents
author_id_str_mv 515e226de019435de4d1f871a82906dc
b17cebaf09b4d737b9378a3581e3de93
author_id_fullname_str_mv 515e226de019435de4d1f871a82906dc_***_Marcus Hull
b17cebaf09b4d737b9378a3581e3de93_***_Steven Kelly
author Marcus Hull
Steven Kelly
author2 Gioele Renzi
Andrea Angeli
Silvia Selleri
Costanza Spadini
Nicolo’ Mezzasalma
Marcus Hull
Steven Kelly
Clemente Capasso
Clotilde S. Cabassi
Fabrizio Carta
Claudiu T. Supuran
format Journal article
container_title Archiv der Pharmazie
container_volume 358
container_issue 7
container_start_page e70062
publishDate 2025
institution Swansea University
issn 0365-6233
1521-4184
doi_str_mv 10.1002/ardp.70062
publisher Wiley
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
active_str 0
description A novel series of compounds was designed and synthesized by combining the distal piperazine nitrogen of the antifungal ketoconazole (KTZ) with primary arylsulfonamides. The aim of this study is to present the basis for a new generation of Malassezia antifungal agents able to inhibit the enzyme lanosterol‐14α‐demethylase (CYP51; EC 1.14.13.70) as well as a newly emergent therapeutic target: carbonic anhydrases (CAs; EC 4.2.1.1). The final compounds showed effective interactions with the intended targets in vitro, as well as KTZ comparable minimum inhibitory concentrations on yeast strains of the Malassezia genus: Malassezia furfur ATCC 14521; Malassezia globosa ATCC MYA 4612; and Malassezia pachydermatis DSM 6172. Overall, the data obtained account for the reported compounds as promising antifungal candidates with high safety profiles for the management of fungal infections.
published_date 2025-07-29T06:55:39Z
_version_ 1858894707210321920
score 11.098807

Similar Items