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The Chemical Space of Marine Antibacterials: Diphenyl Ethers, Benzophenones, Xanthones, and Anthraquinones
The emergence of multiresistant bacteria and the shortage of antibacterials in the drug pipeline creates the need to search for novel agents. Evolution drives the optimization of the structure of marine natural products to act as antibacterial agents. Polyketides are a vast and structurally diverse...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221046/ https://www.ncbi.nlm.nih.gov/pubmed/37241815 http://dx.doi.org/10.3390/molecules28104073 |
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author | Soares, José X. Afonso, Inês Omerbasic, Adaleta Loureiro, Daniela R. P. Pinto, Madalena M. M. Afonso, Carlos M. M. |
author_facet | Soares, José X. Afonso, Inês Omerbasic, Adaleta Loureiro, Daniela R. P. Pinto, Madalena M. M. Afonso, Carlos M. M. |
author_sort | Soares, José X. |
collection | PubMed |
description | The emergence of multiresistant bacteria and the shortage of antibacterials in the drug pipeline creates the need to search for novel agents. Evolution drives the optimization of the structure of marine natural products to act as antibacterial agents. Polyketides are a vast and structurally diverse family of compounds that have been isolated from different marine microorganisms. Within the different polyketides, benzophenones, diphenyl ethers, anthraquinones, and xanthones have shown promising antibacterial activity. In this work, a dataset of 246 marine polyketides has been identified. In order to characterize the chemical space occupied by these marine polyketides, molecular descriptors and fingerprints were calculated. Molecular descriptors were analyzed according to the scaffold, and principal component analysis was performed to identify the relationships among the different descriptors. Generally, the identified marine polyketides are unsaturated, water-insoluble compounds. Among the different polyketides, diphenyl ethers tend to be more lipophilic and non-polar than the remaining classes. Molecular fingerprints were used to group the polyketides according to their molecular similarity into clusters. A total of 76 clusters were obtained, with a loose threshold for the Butina clustering algorithm, highlighting the large structural diversity of the marine polyketides. The large structural diversity was also evidenced by the visualization trees map assembled using the tree map (TMAP) unsupervised machine-learning method. The available antibacterial activity data were examined in terms of bacterial strains, and the activity data were used to rank the compounds according to their antibacterial potential. This potential ranking was used to identify the most promising compounds (four compounds) which can inspire the development of new structural analogs with better potency and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. |
format | Online Article Text |
id | pubmed-10221046 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102210462023-05-28 The Chemical Space of Marine Antibacterials: Diphenyl Ethers, Benzophenones, Xanthones, and Anthraquinones Soares, José X. Afonso, Inês Omerbasic, Adaleta Loureiro, Daniela R. P. Pinto, Madalena M. M. Afonso, Carlos M. M. Molecules Article The emergence of multiresistant bacteria and the shortage of antibacterials in the drug pipeline creates the need to search for novel agents. Evolution drives the optimization of the structure of marine natural products to act as antibacterial agents. Polyketides are a vast and structurally diverse family of compounds that have been isolated from different marine microorganisms. Within the different polyketides, benzophenones, diphenyl ethers, anthraquinones, and xanthones have shown promising antibacterial activity. In this work, a dataset of 246 marine polyketides has been identified. In order to characterize the chemical space occupied by these marine polyketides, molecular descriptors and fingerprints were calculated. Molecular descriptors were analyzed according to the scaffold, and principal component analysis was performed to identify the relationships among the different descriptors. Generally, the identified marine polyketides are unsaturated, water-insoluble compounds. Among the different polyketides, diphenyl ethers tend to be more lipophilic and non-polar than the remaining classes. Molecular fingerprints were used to group the polyketides according to their molecular similarity into clusters. A total of 76 clusters were obtained, with a loose threshold for the Butina clustering algorithm, highlighting the large structural diversity of the marine polyketides. The large structural diversity was also evidenced by the visualization trees map assembled using the tree map (TMAP) unsupervised machine-learning method. The available antibacterial activity data were examined in terms of bacterial strains, and the activity data were used to rank the compounds according to their antibacterial potential. This potential ranking was used to identify the most promising compounds (four compounds) which can inspire the development of new structural analogs with better potency and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. MDPI 2023-05-13 /pmc/articles/PMC10221046/ /pubmed/37241815 http://dx.doi.org/10.3390/molecules28104073 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 Soares, José X. Afonso, Inês Omerbasic, Adaleta Loureiro, Daniela R. P. Pinto, Madalena M. M. Afonso, Carlos M. M. The Chemical Space of Marine Antibacterials: Diphenyl Ethers, Benzophenones, Xanthones, and Anthraquinones |
title | The Chemical Space of Marine Antibacterials: Diphenyl Ethers, Benzophenones, Xanthones, and Anthraquinones |
title_full | The Chemical Space of Marine Antibacterials: Diphenyl Ethers, Benzophenones, Xanthones, and Anthraquinones |
title_fullStr | The Chemical Space of Marine Antibacterials: Diphenyl Ethers, Benzophenones, Xanthones, and Anthraquinones |
title_full_unstemmed | The Chemical Space of Marine Antibacterials: Diphenyl Ethers, Benzophenones, Xanthones, and Anthraquinones |
title_short | The Chemical Space of Marine Antibacterials: Diphenyl Ethers, Benzophenones, Xanthones, and Anthraquinones |
title_sort | chemical space of marine antibacterials: diphenyl ethers, benzophenones, xanthones, and anthraquinones |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221046/ https://www.ncbi.nlm.nih.gov/pubmed/37241815 http://dx.doi.org/10.3390/molecules28104073 |
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