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Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives

Human deaths caused by Gram-negative bacteria keep rising due to the multidrug resistance (MDR) phenomenon. Therefore, it is a priority to develop novel antibiotics with different mechanisms of action. Several bacterial zinc metalloenzymes are becoming attractive targets since they do not show any s...

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Detalles Bibliográficos
Autores principales: Di Leo, Riccardo, Cuffaro, Doretta, Rossello, Armando, Nuti, Elisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254716/
https://www.ncbi.nlm.nih.gov/pubmed/37298854
http://dx.doi.org/10.3390/molecules28114378
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author Di Leo, Riccardo
Cuffaro, Doretta
Rossello, Armando
Nuti, Elisa
author_facet Di Leo, Riccardo
Cuffaro, Doretta
Rossello, Armando
Nuti, Elisa
author_sort Di Leo, Riccardo
collection PubMed
description Human deaths caused by Gram-negative bacteria keep rising due to the multidrug resistance (MDR) phenomenon. Therefore, it is a priority to develop novel antibiotics with different mechanisms of action. Several bacterial zinc metalloenzymes are becoming attractive targets since they do not show any similarities with the human endogenous zinc-metalloproteinases. In the last decades, there has been an increasing interest from both industry and academia in developing new inhibitors against those enzymes involved in lipid A biosynthesis, and bacteria nutrition and sporulation, e.g., UDP-[3-O-(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC), thermolysin (TLN), and pseudolysin (PLN). Nevertheless, targeting these bacterial enzymes is harder than expected and the lack of good clinical candidates suggests that more effort is needed. This review gives an overview of bacterial zinc metalloenzyme inhibitors that have been synthesized so far, highlighting the structural features essential for inhibitory activity and the structure–activity relationships. Our discussion may stimulate and help further studies on bacterial zinc metalloenzyme inhibitors as possible novel antibacterial drugs.
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spelling pubmed-102547162023-06-10 Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives Di Leo, Riccardo Cuffaro, Doretta Rossello, Armando Nuti, Elisa Molecules Review Human deaths caused by Gram-negative bacteria keep rising due to the multidrug resistance (MDR) phenomenon. Therefore, it is a priority to develop novel antibiotics with different mechanisms of action. Several bacterial zinc metalloenzymes are becoming attractive targets since they do not show any similarities with the human endogenous zinc-metalloproteinases. In the last decades, there has been an increasing interest from both industry and academia in developing new inhibitors against those enzymes involved in lipid A biosynthesis, and bacteria nutrition and sporulation, e.g., UDP-[3-O-(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC), thermolysin (TLN), and pseudolysin (PLN). Nevertheless, targeting these bacterial enzymes is harder than expected and the lack of good clinical candidates suggests that more effort is needed. This review gives an overview of bacterial zinc metalloenzyme inhibitors that have been synthesized so far, highlighting the structural features essential for inhibitory activity and the structure–activity relationships. Our discussion may stimulate and help further studies on bacterial zinc metalloenzyme inhibitors as possible novel antibacterial drugs. MDPI 2023-05-27 /pmc/articles/PMC10254716/ /pubmed/37298854 http://dx.doi.org/10.3390/molecules28114378 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Di Leo, Riccardo
Cuffaro, Doretta
Rossello, Armando
Nuti, Elisa
Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives
title Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives
title_full Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives
title_fullStr Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives
title_full_unstemmed Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives
title_short Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives
title_sort bacterial zinc metalloenzyme inhibitors: recent advances and future perspectives
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254716/
https://www.ncbi.nlm.nih.gov/pubmed/37298854
http://dx.doi.org/10.3390/molecules28114378
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