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A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli

Medicinal plants belonging to the genus Berberis may be considered an interesting source of drugs to counteract the problem of antimicrobial multiresistance. The important properties associated with this genus are mainly due to the presence of berberine, an alkaloid with a benzyltetrahydroisoquinoli...

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Autores principales: Di Somma, Angela, Canè, Carolina, Rotondo, Natalie Paola, Cavalluzzi, Maria Maddalena, Lentini, Giovanni, Duilio, Angela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057996/
https://www.ncbi.nlm.nih.gov/pubmed/36982749
http://dx.doi.org/10.3390/ijms24065674
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author Di Somma, Angela
Canè, Carolina
Rotondo, Natalie Paola
Cavalluzzi, Maria Maddalena
Lentini, Giovanni
Duilio, Angela
author_facet Di Somma, Angela
Canè, Carolina
Rotondo, Natalie Paola
Cavalluzzi, Maria Maddalena
Lentini, Giovanni
Duilio, Angela
author_sort Di Somma, Angela
collection PubMed
description Medicinal plants belonging to the genus Berberis may be considered an interesting source of drugs to counteract the problem of antimicrobial multiresistance. The important properties associated with this genus are mainly due to the presence of berberine, an alkaloid with a benzyltetrahydroisoquinoline structure. Berberine is active against both Gram-negative and Gram-positive bacteria, influencing DNA duplication, RNA transcription, protein synthesis, and the integrity of the cell surface structure. Countless studies have shown the enhancement of these beneficial effects following the synthesis of different berberine analogues. Recently, a possible interaction between berberine derivatives and the FtsZ protein was predicted through molecular docking simulations. FtsZ is a highly conserved protein essential for the first step of cell division in bacteria. The importance of FtsZ for the growth of numerous bacterial species and its high conservation make it a perfect candidate for the development of broad-spectrum inhibitors. In this work, we investigate the inhibition mechanisms of the recombinant FtsZ of Escherichia coli by different N-arylmethyl benzodioxolethylamines as berberine simplified analogues appropriately designed to evaluate the effect of structural changes on the interaction with the enzyme. All the compounds determine the inhibition of FtsZ GTPase activity by different mechanisms. The tertiary amine 1c proved to be the best competitive inhibitor, as it causes a remarkable increase in FtsZ K(m) (at 40 μM) and a drastic reduction in its assembly capabilities. Moreover, a fluorescence spectroscopic analysis carried out on 1c demonstrated its strong interaction with FtsZ (K(d) = 26.6 nM). The in vitro results were in agreement with docking simulation studies.
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spelling pubmed-100579962023-03-30 A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli Di Somma, Angela Canè, Carolina Rotondo, Natalie Paola Cavalluzzi, Maria Maddalena Lentini, Giovanni Duilio, Angela Int J Mol Sci Article Medicinal plants belonging to the genus Berberis may be considered an interesting source of drugs to counteract the problem of antimicrobial multiresistance. The important properties associated with this genus are mainly due to the presence of berberine, an alkaloid with a benzyltetrahydroisoquinoline structure. Berberine is active against both Gram-negative and Gram-positive bacteria, influencing DNA duplication, RNA transcription, protein synthesis, and the integrity of the cell surface structure. Countless studies have shown the enhancement of these beneficial effects following the synthesis of different berberine analogues. Recently, a possible interaction between berberine derivatives and the FtsZ protein was predicted through molecular docking simulations. FtsZ is a highly conserved protein essential for the first step of cell division in bacteria. The importance of FtsZ for the growth of numerous bacterial species and its high conservation make it a perfect candidate for the development of broad-spectrum inhibitors. In this work, we investigate the inhibition mechanisms of the recombinant FtsZ of Escherichia coli by different N-arylmethyl benzodioxolethylamines as berberine simplified analogues appropriately designed to evaluate the effect of structural changes on the interaction with the enzyme. All the compounds determine the inhibition of FtsZ GTPase activity by different mechanisms. The tertiary amine 1c proved to be the best competitive inhibitor, as it causes a remarkable increase in FtsZ K(m) (at 40 μM) and a drastic reduction in its assembly capabilities. Moreover, a fluorescence spectroscopic analysis carried out on 1c demonstrated its strong interaction with FtsZ (K(d) = 26.6 nM). The in vitro results were in agreement with docking simulation studies. MDPI 2023-03-16 /pmc/articles/PMC10057996/ /pubmed/36982749 http://dx.doi.org/10.3390/ijms24065674 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 Article
Di Somma, Angela
Canè, Carolina
Rotondo, Natalie Paola
Cavalluzzi, Maria Maddalena
Lentini, Giovanni
Duilio, Angela
A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli
title A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli
title_full A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli
title_fullStr A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli
title_full_unstemmed A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli
title_short A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli
title_sort comparative study of the inhibitory action of berberine derivatives on the recombinant protein ftsz of e. coli
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057996/
https://www.ncbi.nlm.nih.gov/pubmed/36982749
http://dx.doi.org/10.3390/ijms24065674
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