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Identification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts

Tuberculosis (TB) remains a public health crisis, requiring the urgent identification of new anti-mycobacterial drugs. We screened several organic and aqueous marine invertebrate extracts for their in vitro inhibitory activity against the causative organism, Mycobacterium tuberculosis. Here, we repo...

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Autores principales: Acquah, Kojo Sekyi, Beukes, Denzil R., Seldon, Ronnett, Jordaan, Audrey, Sunassee, Suthananda N., Warner, Digby F., Gammon, David W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880526/
https://www.ncbi.nlm.nih.gov/pubmed/35200753
http://dx.doi.org/10.3390/medicines9020009
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author Acquah, Kojo Sekyi
Beukes, Denzil R.
Seldon, Ronnett
Jordaan, Audrey
Sunassee, Suthananda N.
Warner, Digby F.
Gammon, David W.
author_facet Acquah, Kojo Sekyi
Beukes, Denzil R.
Seldon, Ronnett
Jordaan, Audrey
Sunassee, Suthananda N.
Warner, Digby F.
Gammon, David W.
author_sort Acquah, Kojo Sekyi
collection PubMed
description Tuberculosis (TB) remains a public health crisis, requiring the urgent identification of new anti-mycobacterial drugs. We screened several organic and aqueous marine invertebrate extracts for their in vitro inhibitory activity against the causative organism, Mycobacterium tuberculosis. Here, we report the results obtained for 54 marine invertebrate extracts. The chemical components of two of the extracts were dereplicated, using (1)H NMR and HR-LCMS with GNPS molecular networking, and these extracts were further subjected to an activity-guided isolation process to purify the bioactive components. Hyrtios reticulatus yielded heteronemin 1 and Jaspis splendens was found to produce the bengamide class of compounds, of which bengamides P 2 and Q 3 were isolated, while a new derivative, bengamide S 5, was putatively identified and its structure predicted, based on the similarity of its MS/MS fragmentation pattern to those of other bengamides. The isolated bioactive metabolites and semi-pure fractions exhibited M. tuberculosis growth inhibitory activity, in the range <0.24 to 62.50 µg/mL. This study establishes the bengamides as potent antitubercular compounds, with the first report of whole-cell antitubercular activity of bengamides P 2 and Q 3.
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spelling pubmed-88805262022-02-26 Identification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts Acquah, Kojo Sekyi Beukes, Denzil R. Seldon, Ronnett Jordaan, Audrey Sunassee, Suthananda N. Warner, Digby F. Gammon, David W. Medicines (Basel) Article Tuberculosis (TB) remains a public health crisis, requiring the urgent identification of new anti-mycobacterial drugs. We screened several organic and aqueous marine invertebrate extracts for their in vitro inhibitory activity against the causative organism, Mycobacterium tuberculosis. Here, we report the results obtained for 54 marine invertebrate extracts. The chemical components of two of the extracts were dereplicated, using (1)H NMR and HR-LCMS with GNPS molecular networking, and these extracts were further subjected to an activity-guided isolation process to purify the bioactive components. Hyrtios reticulatus yielded heteronemin 1 and Jaspis splendens was found to produce the bengamide class of compounds, of which bengamides P 2 and Q 3 were isolated, while a new derivative, bengamide S 5, was putatively identified and its structure predicted, based on the similarity of its MS/MS fragmentation pattern to those of other bengamides. The isolated bioactive metabolites and semi-pure fractions exhibited M. tuberculosis growth inhibitory activity, in the range <0.24 to 62.50 µg/mL. This study establishes the bengamides as potent antitubercular compounds, with the first report of whole-cell antitubercular activity of bengamides P 2 and Q 3. MDPI 2022-01-28 /pmc/articles/PMC8880526/ /pubmed/35200753 http://dx.doi.org/10.3390/medicines9020009 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 Article
Acquah, Kojo Sekyi
Beukes, Denzil R.
Seldon, Ronnett
Jordaan, Audrey
Sunassee, Suthananda N.
Warner, Digby F.
Gammon, David W.
Identification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts
title Identification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts
title_full Identification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts
title_fullStr Identification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts
title_full_unstemmed Identification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts
title_short Identification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts
title_sort identification of antimycobacterial natural products from a library of marine invertebrate extracts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880526/
https://www.ncbi.nlm.nih.gov/pubmed/35200753
http://dx.doi.org/10.3390/medicines9020009
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