Cargando…
Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents
The disease-free existence of humans is constantly under attack by a variety of infections caused by a variety of organisms including bacteria. Notable among the bacteria is Staphylococcus aureus which is an etiological organism for infections including impetigo, folliculitis, and furuncles. The res...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635275/ https://www.ncbi.nlm.nih.gov/pubmed/37954245 http://dx.doi.org/10.3389/fmicb.2023.1279082 |
_version_ | 1785132958382817280 |
---|---|
author | Bourhia, Mohammed Shahab, Muhammad Zheng, Guojun Bin Jardan, Yousef A. Sitotaw, Baye Ouahmane, Lahcen Khallouki, Farid |
author_facet | Bourhia, Mohammed Shahab, Muhammad Zheng, Guojun Bin Jardan, Yousef A. Sitotaw, Baye Ouahmane, Lahcen Khallouki, Farid |
author_sort | Bourhia, Mohammed |
collection | PubMed |
description | The disease-free existence of humans is constantly under attack by a variety of infections caused by a variety of organisms including bacteria. Notable among the bacteria is Staphylococcus aureus which is an etiological organism for infections including impetigo, folliculitis, and furuncles. The response of the human immune system against this disease is often neutralized by the production of a pigment called Staphyloxanthin (STX) via a series of reactions mediated by several enzymes. Among these enzymes, dehydrosqualene synthase, also known as CrtM, has emerged as a viable drug target due to its role in mediating the first step of the pathway. Consequently, this study employs molecular modeling approaches including molecular docking, quantum mechanical calculations, and molecular dynamics (MD) simulations among others to investigate the potential of napthyridine derivatives to serve as inhibitors of the CrtM. The results of the study revealed the high binding affinities of the compounds for the target as demonstrated by their docking scores, while further subjection to screening pipeline aimed at determining their fitness for development into drugs revealed just one compound namely 6-[[1-[(2-fluorophenyl) methyl]triazol-4-yl]methoxy]-4-oxo-1H-1,5-naphthyridine-3-carboxylic acid as the compound with good drug-like, pharmacokinetics, and toxicity properties profiles. A 100 ns-long MD simulation of the complexes formed after molecular docking revealed the stable interaction of the compound with the target. Ultimately, this study can be a promising outlet to discover a weapon to fight against clinically resistant bacteria, however, further experimental studies are suggested to carry out in the wet lab, pre-clinical, and clinical levels. |
format | Online Article Text |
id | pubmed-10635275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106352752023-11-10 Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents Bourhia, Mohammed Shahab, Muhammad Zheng, Guojun Bin Jardan, Yousef A. Sitotaw, Baye Ouahmane, Lahcen Khallouki, Farid Front Microbiol Microbiology The disease-free existence of humans is constantly under attack by a variety of infections caused by a variety of organisms including bacteria. Notable among the bacteria is Staphylococcus aureus which is an etiological organism for infections including impetigo, folliculitis, and furuncles. The response of the human immune system against this disease is often neutralized by the production of a pigment called Staphyloxanthin (STX) via a series of reactions mediated by several enzymes. Among these enzymes, dehydrosqualene synthase, also known as CrtM, has emerged as a viable drug target due to its role in mediating the first step of the pathway. Consequently, this study employs molecular modeling approaches including molecular docking, quantum mechanical calculations, and molecular dynamics (MD) simulations among others to investigate the potential of napthyridine derivatives to serve as inhibitors of the CrtM. The results of the study revealed the high binding affinities of the compounds for the target as demonstrated by their docking scores, while further subjection to screening pipeline aimed at determining their fitness for development into drugs revealed just one compound namely 6-[[1-[(2-fluorophenyl) methyl]triazol-4-yl]methoxy]-4-oxo-1H-1,5-naphthyridine-3-carboxylic acid as the compound with good drug-like, pharmacokinetics, and toxicity properties profiles. A 100 ns-long MD simulation of the complexes formed after molecular docking revealed the stable interaction of the compound with the target. Ultimately, this study can be a promising outlet to discover a weapon to fight against clinically resistant bacteria, however, further experimental studies are suggested to carry out in the wet lab, pre-clinical, and clinical levels. Frontiers Media S.A. 2023-10-24 /pmc/articles/PMC10635275/ /pubmed/37954245 http://dx.doi.org/10.3389/fmicb.2023.1279082 Text en Copyright © 2023 Bourhia, Shahab, Zheng, Bin Jardan, Sitotaw, Ouahmane and Khallouki. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Bourhia, Mohammed Shahab, Muhammad Zheng, Guojun Bin Jardan, Yousef A. Sitotaw, Baye Ouahmane, Lahcen Khallouki, Farid Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents |
title | Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents |
title_full | Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents |
title_fullStr | Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents |
title_full_unstemmed | Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents |
title_short | Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents |
title_sort | napthyridine-derived compounds as promising inhibitors for staphylococcus aureus crtm: a primer for the discovery of potential anti-staphylococcus aureus agents |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635275/ https://www.ncbi.nlm.nih.gov/pubmed/37954245 http://dx.doi.org/10.3389/fmicb.2023.1279082 |
work_keys_str_mv | AT bourhiamohammed napthyridinederivedcompoundsaspromisinginhibitorsforstaphylococcusaureuscrtmaprimerforthediscoveryofpotentialantistaphylococcusaureusagents AT shahabmuhammad napthyridinederivedcompoundsaspromisinginhibitorsforstaphylococcusaureuscrtmaprimerforthediscoveryofpotentialantistaphylococcusaureusagents AT zhengguojun napthyridinederivedcompoundsaspromisinginhibitorsforstaphylococcusaureuscrtmaprimerforthediscoveryofpotentialantistaphylococcusaureusagents AT binjardanyousefa napthyridinederivedcompoundsaspromisinginhibitorsforstaphylococcusaureuscrtmaprimerforthediscoveryofpotentialantistaphylococcusaureusagents AT sitotawbaye napthyridinederivedcompoundsaspromisinginhibitorsforstaphylococcusaureuscrtmaprimerforthediscoveryofpotentialantistaphylococcusaureusagents AT ouahmanelahcen napthyridinederivedcompoundsaspromisinginhibitorsforstaphylococcusaureuscrtmaprimerforthediscoveryofpotentialantistaphylococcusaureusagents AT khalloukifarid napthyridinederivedcompoundsaspromisinginhibitorsforstaphylococcusaureuscrtmaprimerforthediscoveryofpotentialantistaphylococcusaureusagents |