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Novel Effective Fluorinated Benzothiophene-Indole Hybrid Antibacterials against S. aureus and MRSA Strains

Increasing antibacterial drug resistance threatens global health, unfortunately, however, efforts to find novel antibacterial agents have been scaled back by the pharmaceutical industry due to concerns about a poor return on investment. Nevertheless, there is an urgent need to find novel antibacteri...

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Autores principales: Seethaler, Marius, Hertlein, Tobias, Hopke, Elisa, Köhling, Paul, Ohlsen, Knut, Lalk, Michael, Hilgeroth, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502754/
https://www.ncbi.nlm.nih.gov/pubmed/36145359
http://dx.doi.org/10.3390/ph15091138
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author Seethaler, Marius
Hertlein, Tobias
Hopke, Elisa
Köhling, Paul
Ohlsen, Knut
Lalk, Michael
Hilgeroth, Andreas
author_facet Seethaler, Marius
Hertlein, Tobias
Hopke, Elisa
Köhling, Paul
Ohlsen, Knut
Lalk, Michael
Hilgeroth, Andreas
author_sort Seethaler, Marius
collection PubMed
description Increasing antibacterial drug resistance threatens global health, unfortunately, however, efforts to find novel antibacterial agents have been scaled back by the pharmaceutical industry due to concerns about a poor return on investment. Nevertheless, there is an urgent need to find novel antibacterial compounds to combat antibacterial drug resistance. The synthesis of novel drugs from natural sources is mostly cost-intensive due to those drugs’ complicated structures. Therefore, it is necessary to find novel antibacterials by simple synthesis to become more attractive for industrial production. We succeeded in the discovery of four antibacterial compound (sub)classes accessible in a simple one-pot reaction based on fluorinated benzothiophene-indole hybrids. They have been evaluated against various S. aureus and MRSA strains. Structure- and substituent-dependent activities have been found within the (sub)classes and promising lead compounds have been identified. In addition, bacterial pyruvate kinase was found to be the molecular target of the active compounds. In conclusion, simple one-pot synthesis of benzothiophene-indoles represents a promising strategy for the search of novel antimicrobial compounds.
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spelling pubmed-95027542022-09-24 Novel Effective Fluorinated Benzothiophene-Indole Hybrid Antibacterials against S. aureus and MRSA Strains Seethaler, Marius Hertlein, Tobias Hopke, Elisa Köhling, Paul Ohlsen, Knut Lalk, Michael Hilgeroth, Andreas Pharmaceuticals (Basel) Communication Increasing antibacterial drug resistance threatens global health, unfortunately, however, efforts to find novel antibacterial agents have been scaled back by the pharmaceutical industry due to concerns about a poor return on investment. Nevertheless, there is an urgent need to find novel antibacterial compounds to combat antibacterial drug resistance. The synthesis of novel drugs from natural sources is mostly cost-intensive due to those drugs’ complicated structures. Therefore, it is necessary to find novel antibacterials by simple synthesis to become more attractive for industrial production. We succeeded in the discovery of four antibacterial compound (sub)classes accessible in a simple one-pot reaction based on fluorinated benzothiophene-indole hybrids. They have been evaluated against various S. aureus and MRSA strains. Structure- and substituent-dependent activities have been found within the (sub)classes and promising lead compounds have been identified. In addition, bacterial pyruvate kinase was found to be the molecular target of the active compounds. In conclusion, simple one-pot synthesis of benzothiophene-indoles represents a promising strategy for the search of novel antimicrobial compounds. MDPI 2022-09-13 /pmc/articles/PMC9502754/ /pubmed/36145359 http://dx.doi.org/10.3390/ph15091138 Text en © 2022 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 Communication
Seethaler, Marius
Hertlein, Tobias
Hopke, Elisa
Köhling, Paul
Ohlsen, Knut
Lalk, Michael
Hilgeroth, Andreas
Novel Effective Fluorinated Benzothiophene-Indole Hybrid Antibacterials against S. aureus and MRSA Strains
title Novel Effective Fluorinated Benzothiophene-Indole Hybrid Antibacterials against S. aureus and MRSA Strains
title_full Novel Effective Fluorinated Benzothiophene-Indole Hybrid Antibacterials against S. aureus and MRSA Strains
title_fullStr Novel Effective Fluorinated Benzothiophene-Indole Hybrid Antibacterials against S. aureus and MRSA Strains
title_full_unstemmed Novel Effective Fluorinated Benzothiophene-Indole Hybrid Antibacterials against S. aureus and MRSA Strains
title_short Novel Effective Fluorinated Benzothiophene-Indole Hybrid Antibacterials against S. aureus and MRSA Strains
title_sort novel effective fluorinated benzothiophene-indole hybrid antibacterials against s. aureus and mrsa strains
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502754/
https://www.ncbi.nlm.nih.gov/pubmed/36145359
http://dx.doi.org/10.3390/ph15091138
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