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Design and Synthesis of Ketoconazole Derivatives as Innovative Anti‐Infective Agents
,
Andrea Angeli ,
Silvia Selleri,
Costanza Spadini ,
Nicolo’ Mezzasalma,
Marcus Hull,
Steven Kelly,
Clemente Capasso,
Clotilde S. Cabassi ,
Fabrizio Carta ,
Claudiu T. Supuran
Archiv der Pharmazie, Volume: 358, Issue: 7, Start page: e70062
Swansea University Authors: Marcus Hull, Steven Kelly
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© 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).
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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...
| Published in: | Archiv der Pharmazie |
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| ISSN: | 0365-6233 1521-4184 |
| Published: |
Wiley
2025
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| Online Access: |
Check full text
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa70049 |
| 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‐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. |
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| Keywords: |
14α-demethylase, antifungals, carbonic anhydrases, fungi, Malassezia |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
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. |
| Issue: |
7 |
| Start Page: |
e70062 |