Schiff bases of sulphonamides as a new class of antifungal agent against multidrug-resistant Candida auris

Asad Hamad; Yiyuan Chen; Mohsin A. Khan; Shirin Jamshidi; Naima Saeed; Melanie Clifford; Charlotte Hind; J. Mark Sutton; Khondaker Miraz Rahman

doi:10.1002/mbo3.1218

Schiff bases of sulphonamides as a new class of antifungal agent against multidrug-resistant Candida auris

Asad Hamad, Yiyuan Chen, Mohsin A. Khan, Shirin Jamshidi, Naima Saeed, Melanie Clifford, Charlotte Hind, J. Mark Sutton, Khondaker Miraz Rahman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Invasive Candida infections in hospitalized and immunocompromised or critically ill patients have become an important cause of morbidity and mortality. There are increasing reports of multidrug resistance in several Candida species that cause Candidemia, including C. glabrata and C. auris, with limited numbers of antifungal agents available to treat patients with invasive Candida infections. Therefore, there is an urgent need to discover new antifungal agents that work against multidrug-resistant Candida species, particularly C. auris, which has been identified as an emerging global pathogen. In this article, we report a new class of antifungal agents, the Schiff bases of sulphonamides, that show activity against all Candida species tested, with an MIC range of 4–32 µg/ml. Compound 2b showed activity against C. glabrata and a panel of fluconazole-resistant C. auris strains, with MICs of 4–16 µg/ml. The drug-like nature of these Schiff bases offers opportunities to optimize these compounds with medicinal chemistry techniques to obtain more potent analogs that can be progressed toward pre-clinical evaluation.

Original language	English
Article number	e1218
Number of pages	8
Journal	MicrobiologyOpen
Volume	10
Issue number	4
Early online date	23 Jul 2021
DOIs	https://doi.org/10.1002/mbo3.1218
Publication status	Published - Aug 2021

Bibliographical note

Funding Information: PHE, Grant/Award Number: 109502, 109505 and 111742; King’s College London.

We thank HEC Pakistan for supporting AH's doctoral placement at King's College London. We acknowledge funding from PHE Pipeline (project 109502) and grant-in-aid projects (Project 109505 and 111742) for this work. We also thank Ginny Moore of Public Health England for providing C. auris strains isolated from UK hospitals.

Open Access: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Publisher Copyright: © 2021 The Authors. Microbiology Open published by John Wiley & Sons Ltd.

Citation: Hamad, A., Chen, Y., Khan, M. A., Jamshidi, S., Saeed, N., Clifford, M., Hind, C., Sutton, J. M., & Rahman, K. M. (2021). Schiff bases of sulphonamides as a new class of antifungal agent against multidrug-resistant Candida auris. MicrobiologyOpen, 10, e1218.

DOI: https://doi.org/10.1002/mbo3.1218

Keywords

Candida auris
Schiff bases
antifungal resistance
candidemia
sulphonamides

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Hamad2021SchiffBasesofSulphonamidesAsANewClassofAntifungalMicrobiologyOpenFinal published version, 695 KBLicence: CC BY

Cite this

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title = "Schiff bases of sulphonamides as a new class of antifungal agent against multidrug-resistant Candida auris",

abstract = "Invasive Candida infections in hospitalized and immunocompromised or critically ill patients have become an important cause of morbidity and mortality. There are increasing reports of multidrug resistance in several Candida species that cause Candidemia, including C. glabrata and C. auris, with limited numbers of antifungal agents available to treat patients with invasive Candida infections. Therefore, there is an urgent need to discover new antifungal agents that work against multidrug-resistant Candida species, particularly C. auris, which has been identified as an emerging global pathogen. In this article, we report a new class of antifungal agents, the Schiff bases of sulphonamides, that show activity against all Candida species tested, with an MIC range of 4–32 µg/ml. Compound 2b showed activity against C. glabrata and a panel of fluconazole-resistant C. auris strains, with MICs of 4–16 µg/ml. The drug-like nature of these Schiff bases offers opportunities to optimize these compounds with medicinal chemistry techniques to obtain more potent analogs that can be progressed toward pre-clinical evaluation.",

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author = "Asad Hamad and Yiyuan Chen and Khan, {Mohsin A.} and Shirin Jamshidi and Naima Saeed and Melanie Clifford and Charlotte Hind and Sutton, {J. Mark} and Rahman, {Khondaker Miraz}",

note = "Funding Information: PHE, Grant/Award Number: 109502, 109505 and 111742; King{\textquoteright}s College London. We thank HEC Pakistan for supporting AH's doctoral placement at King's College London. We acknowledge funding from PHE Pipeline (project 109502) and grant-in-aid projects (Project 109505 and 111742) for this work. We also thank Ginny Moore of Public Health England for providing C. auris strains isolated from UK hospitals. Open Access: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Publisher Copyright: {\textcopyright} 2021 The Authors. Microbiology Open published by John Wiley & Sons Ltd. Citation: Hamad, A., Chen, Y., Khan, M. A., Jamshidi, S., Saeed, N., Clifford, M., Hind, C., Sutton, J. M., & Rahman, K. M. (2021). Schiff bases of sulphonamides as a new class of antifungal agent against multidrug-resistant Candida auris. MicrobiologyOpen, 10, e1218. DOI: https://doi.org/10.1002/mbo3.1218 ",

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AU - Hamad, Asad

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AU - Khan, Mohsin A.

AU - Jamshidi, Shirin

AU - Saeed, Naima

AU - Clifford, Melanie

AU - Hind, Charlotte

AU - Sutton, J. Mark

AU - Rahman, Khondaker Miraz

N1 - Funding Information: PHE, Grant/Award Number: 109502, 109505 and 111742; King’s College London. We thank HEC Pakistan for supporting AH's doctoral placement at King's College London. We acknowledge funding from PHE Pipeline (project 109502) and grant-in-aid projects (Project 109505 and 111742) for this work. We also thank Ginny Moore of Public Health England for providing C. auris strains isolated from UK hospitals. Open Access: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Publisher Copyright: © 2021 The Authors. Microbiology Open published by John Wiley & Sons Ltd. Citation: Hamad, A., Chen, Y., Khan, M. A., Jamshidi, S., Saeed, N., Clifford, M., Hind, C., Sutton, J. M., & Rahman, K. M. (2021). Schiff bases of sulphonamides as a new class of antifungal agent against multidrug-resistant Candida auris. MicrobiologyOpen, 10, e1218. DOI: https://doi.org/10.1002/mbo3.1218

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N2 - Invasive Candida infections in hospitalized and immunocompromised or critically ill patients have become an important cause of morbidity and mortality. There are increasing reports of multidrug resistance in several Candida species that cause Candidemia, including C. glabrata and C. auris, with limited numbers of antifungal agents available to treat patients with invasive Candida infections. Therefore, there is an urgent need to discover new antifungal agents that work against multidrug-resistant Candida species, particularly C. auris, which has been identified as an emerging global pathogen. In this article, we report a new class of antifungal agents, the Schiff bases of sulphonamides, that show activity against all Candida species tested, with an MIC range of 4–32 µg/ml. Compound 2b showed activity against C. glabrata and a panel of fluconazole-resistant C. auris strains, with MICs of 4–16 µg/ml. The drug-like nature of these Schiff bases offers opportunities to optimize these compounds with medicinal chemistry techniques to obtain more potent analogs that can be progressed toward pre-clinical evaluation.

AB - Invasive Candida infections in hospitalized and immunocompromised or critically ill patients have become an important cause of morbidity and mortality. There are increasing reports of multidrug resistance in several Candida species that cause Candidemia, including C. glabrata and C. auris, with limited numbers of antifungal agents available to treat patients with invasive Candida infections. Therefore, there is an urgent need to discover new antifungal agents that work against multidrug-resistant Candida species, particularly C. auris, which has been identified as an emerging global pathogen. In this article, we report a new class of antifungal agents, the Schiff bases of sulphonamides, that show activity against all Candida species tested, with an MIC range of 4–32 µg/ml. Compound 2b showed activity against C. glabrata and a panel of fluconazole-resistant C. auris strains, with MICs of 4–16 µg/ml. The drug-like nature of these Schiff bases offers opportunities to optimize these compounds with medicinal chemistry techniques to obtain more potent analogs that can be progressed toward pre-clinical evaluation.

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ER -

Schiff bases of sulphonamides as a new class of antifungal agent against multidrug-resistant Candida auris

Abstract

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