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New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action
This work reports a detailed characterization of the antimicrobial profile of two trimethoprim-like molecules (compounds 1a and 1b) identified in previous studies. Both molecules displayed remarkable antimicrobial activity, particularly when combined with sulfamethoxazole. In disk diffusion assays o...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231229/ https://www.ncbi.nlm.nih.gov/pubmed/34204647 http://dx.doi.org/10.3390/antibiotics10060709 |
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author | Jorba, Marta Pedrola, Marina Ghashghaei, Ouldouz Herráez, Rocío Campos-Vicens, Lluis Luque, Franciso Javier Lavilla, Rodolfo Viñas, Miguel |
author_facet | Jorba, Marta Pedrola, Marina Ghashghaei, Ouldouz Herráez, Rocío Campos-Vicens, Lluis Luque, Franciso Javier Lavilla, Rodolfo Viñas, Miguel |
author_sort | Jorba, Marta |
collection | PubMed |
description | This work reports a detailed characterization of the antimicrobial profile of two trimethoprim-like molecules (compounds 1a and 1b) identified in previous studies. Both molecules displayed remarkable antimicrobial activity, particularly when combined with sulfamethoxazole. In disk diffusion assays on Petri dishes, compounds 1a and 1b showed synergistic effects with colistin. Specifically, in combinations with low concentrations of colistin, very large increases in the activities of compounds 1a and 1b were determined, as demonstrated by alterations in the kinetics of bacterial growth despite only slight changes in the fractional inhibitory concentration index. The effect of colistin may be to increase the rate of antibiotic entry while reducing efflux pump activity. Compounds 1a and 1b were susceptible to extrusion by efflux pumps, whereas the inhibitor phenylalanine arginyl β-naphthylamide (PAβN) exerted effects similar to those of colistin. The interactions between the target enzyme (dihydrofolate reductase), the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH), and the studied molecules were explored using enzymology tools and computational chemistry. A model based on docking results is reported. |
format | Online Article Text |
id | pubmed-8231229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82312292021-06-26 New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action Jorba, Marta Pedrola, Marina Ghashghaei, Ouldouz Herráez, Rocío Campos-Vicens, Lluis Luque, Franciso Javier Lavilla, Rodolfo Viñas, Miguel Antibiotics (Basel) Article This work reports a detailed characterization of the antimicrobial profile of two trimethoprim-like molecules (compounds 1a and 1b) identified in previous studies. Both molecules displayed remarkable antimicrobial activity, particularly when combined with sulfamethoxazole. In disk diffusion assays on Petri dishes, compounds 1a and 1b showed synergistic effects with colistin. Specifically, in combinations with low concentrations of colistin, very large increases in the activities of compounds 1a and 1b were determined, as demonstrated by alterations in the kinetics of bacterial growth despite only slight changes in the fractional inhibitory concentration index. The effect of colistin may be to increase the rate of antibiotic entry while reducing efflux pump activity. Compounds 1a and 1b were susceptible to extrusion by efflux pumps, whereas the inhibitor phenylalanine arginyl β-naphthylamide (PAβN) exerted effects similar to those of colistin. The interactions between the target enzyme (dihydrofolate reductase), the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH), and the studied molecules were explored using enzymology tools and computational chemistry. A model based on docking results is reported. MDPI 2021-06-12 /pmc/articles/PMC8231229/ /pubmed/34204647 http://dx.doi.org/10.3390/antibiotics10060709 Text en © 2021 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 Jorba, Marta Pedrola, Marina Ghashghaei, Ouldouz Herráez, Rocío Campos-Vicens, Lluis Luque, Franciso Javier Lavilla, Rodolfo Viñas, Miguel New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action |
title | New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action |
title_full | New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action |
title_fullStr | New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action |
title_full_unstemmed | New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action |
title_short | New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action |
title_sort | new trimethoprim-like molecules: bacteriological evaluation and insights into their action |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231229/ https://www.ncbi.nlm.nih.gov/pubmed/34204647 http://dx.doi.org/10.3390/antibiotics10060709 |
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