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Bioassay Guided Isolation and Docking Studies of a Potential β-Lactamase Inhibitor from Clutia myricoides
Infectious diseases are the second major cause of death worldwide, and the ability to resist multiple classes of antibiotics is the key factor in enabling pathogenic organisms to survive and spread in the nosocomial environment. Unfortunately, the available β-lactamase inhibitors are not efficient a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321312/ https://www.ncbi.nlm.nih.gov/pubmed/32486455 http://dx.doi.org/10.3390/molecules25112566 |
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author | Elfaky, Mahmoud A. El-Halawany, Ali M. Koshak, Abdulrahman E. Alshali, Khalid Z. El-Araby, Moustafa E. Khayat, Maan T. Abdallah, Hossam M. |
author_facet | Elfaky, Mahmoud A. El-Halawany, Ali M. Koshak, Abdulrahman E. Alshali, Khalid Z. El-Araby, Moustafa E. Khayat, Maan T. Abdallah, Hossam M. |
author_sort | Elfaky, Mahmoud A. |
collection | PubMed |
description | Infectious diseases are the second major cause of death worldwide, and the ability to resist multiple classes of antibiotics is the key factor in enabling pathogenic organisms to survive and spread in the nosocomial environment. Unfortunately, the available β-lactamase inhibitors are not efficient against β-lactamase B, C, and D which necessitates discovering either broad spectrum β-lactamase inhibitors or new β-lactam antibiotics resistant to bacterial enzymes. In this regard, products of natural origin have prompted the disclosure of new compounds and medicinal leads. Chloroform fraction of Clutia myricoides (Soa’bor) showed a pronounced activity against extended-spectrum β-lactamase (ESBL) strains. Bio-guided fractionation resulted in isolation of two new compounds; 2-methoxy chrysophanol (2) and Saudin-I (5) in addition to three known compounds that were identified as chrysophanol (1), stigmasterol (3) and β-sitosterol (4). Antibacterial and anti ESBL activities of the isolated compounds were performed. No antibacterial activities were detected for any of the tested compounds. Meanwhile, compound 2 showed promising anti ESBL activity. Compound 2 has shown an obvious activity against K. pneumoniae ATCC 700603 with a marked enlargement of inhibition zones (>5mm) in combination with third generation cephalosporin antibiotics. To further understand the mechanism of action of compound 2, molecular docking was carried out against CTX-M-27 ESBL. The results showed binding site interactions strikingly different from its analogue, compound 1, allowing compound 2 to be active against ESBL. These results proposed the concomitant use of these active compounds with antibiotics that would increase their efficiency. Nevertheless, the interaction between this active compound and antibiotics should be taken into consideration. Therefore, in order to evaluate the safety of this active compound, further in vitro and in vivo toxicity assays must be carried out. |
format | Online Article Text |
id | pubmed-7321312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73213122020-06-29 Bioassay Guided Isolation and Docking Studies of a Potential β-Lactamase Inhibitor from Clutia myricoides Elfaky, Mahmoud A. El-Halawany, Ali M. Koshak, Abdulrahman E. Alshali, Khalid Z. El-Araby, Moustafa E. Khayat, Maan T. Abdallah, Hossam M. Molecules Article Infectious diseases are the second major cause of death worldwide, and the ability to resist multiple classes of antibiotics is the key factor in enabling pathogenic organisms to survive and spread in the nosocomial environment. Unfortunately, the available β-lactamase inhibitors are not efficient against β-lactamase B, C, and D which necessitates discovering either broad spectrum β-lactamase inhibitors or new β-lactam antibiotics resistant to bacterial enzymes. In this regard, products of natural origin have prompted the disclosure of new compounds and medicinal leads. Chloroform fraction of Clutia myricoides (Soa’bor) showed a pronounced activity against extended-spectrum β-lactamase (ESBL) strains. Bio-guided fractionation resulted in isolation of two new compounds; 2-methoxy chrysophanol (2) and Saudin-I (5) in addition to three known compounds that were identified as chrysophanol (1), stigmasterol (3) and β-sitosterol (4). Antibacterial and anti ESBL activities of the isolated compounds were performed. No antibacterial activities were detected for any of the tested compounds. Meanwhile, compound 2 showed promising anti ESBL activity. Compound 2 has shown an obvious activity against K. pneumoniae ATCC 700603 with a marked enlargement of inhibition zones (>5mm) in combination with third generation cephalosporin antibiotics. To further understand the mechanism of action of compound 2, molecular docking was carried out against CTX-M-27 ESBL. The results showed binding site interactions strikingly different from its analogue, compound 1, allowing compound 2 to be active against ESBL. These results proposed the concomitant use of these active compounds with antibiotics that would increase their efficiency. Nevertheless, the interaction between this active compound and antibiotics should be taken into consideration. Therefore, in order to evaluate the safety of this active compound, further in vitro and in vivo toxicity assays must be carried out. MDPI 2020-05-31 /pmc/articles/PMC7321312/ /pubmed/32486455 http://dx.doi.org/10.3390/molecules25112566 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Elfaky, Mahmoud A. El-Halawany, Ali M. Koshak, Abdulrahman E. Alshali, Khalid Z. El-Araby, Moustafa E. Khayat, Maan T. Abdallah, Hossam M. Bioassay Guided Isolation and Docking Studies of a Potential β-Lactamase Inhibitor from Clutia myricoides |
title | Bioassay Guided Isolation and Docking Studies of a Potential β-Lactamase Inhibitor from Clutia myricoides |
title_full | Bioassay Guided Isolation and Docking Studies of a Potential β-Lactamase Inhibitor from Clutia myricoides |
title_fullStr | Bioassay Guided Isolation and Docking Studies of a Potential β-Lactamase Inhibitor from Clutia myricoides |
title_full_unstemmed | Bioassay Guided Isolation and Docking Studies of a Potential β-Lactamase Inhibitor from Clutia myricoides |
title_short | Bioassay Guided Isolation and Docking Studies of a Potential β-Lactamase Inhibitor from Clutia myricoides |
title_sort | bioassay guided isolation and docking studies of a potential β-lactamase inhibitor from clutia myricoides |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321312/ https://www.ncbi.nlm.nih.gov/pubmed/32486455 http://dx.doi.org/10.3390/molecules25112566 |
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