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Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein
Tuberculosis continues to be a great source of concern in global health because of the large reservoir of humans infected with the bacilli and the appearance of clinical isolates resistant to a wide array of anti-tuberculosis drugs. New drugs with novel mechanisms of action on new targets are urgent...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151991/ https://www.ncbi.nlm.nih.gov/pubmed/28757569 http://dx.doi.org/10.3390/molecules22081245 |
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author | Suarez, María Angélica Valencia, Jhesua Cadena, Christian Camilo Maiti, Raktim Datta, Chandreyee Puerto, Gloria Isaza, José Hipólito San Juan, Homero Nagaraja, Valakunja Guzman, Juan David |
author_facet | Suarez, María Angélica Valencia, Jhesua Cadena, Christian Camilo Maiti, Raktim Datta, Chandreyee Puerto, Gloria Isaza, José Hipólito San Juan, Homero Nagaraja, Valakunja Guzman, Juan David |
author_sort | Suarez, María Angélica |
collection | PubMed |
description | Tuberculosis continues to be a great source of concern in global health because of the large reservoir of humans infected with the bacilli and the appearance of clinical isolates resistant to a wide array of anti-tuberculosis drugs. New drugs with novel mechanisms of action on new targets are urgently required to reduce global tuberculosis burden. Mycobacterium tuberculosis nucleoid associated protein (NAP) HU has been shown to be druggable and essential for the organism’s survival. In this study, four diarylethenes were synthesized using a one-pot decarboxylated Heck-coupling of coumaric acids with iodoanisoles. The prepared compounds 1–4 were tested for their in vitro growth inhibition of M. tuberculosis H37Rv using the spot culture growth inhibition assay, displaying minimum inhibitory concentrations between 9 and 22 µM. Their cytotoxicity against BHK-21 cell line showed half inhibition at concentrations between 98 and 729 µM. The most selective hit (SI = 81), demonstrated inhibition of M. tuberculosis HU protein involved in maintaining bacterial genome architecture. |
format | Online Article Text |
id | pubmed-6151991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61519912018-11-13 Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein Suarez, María Angélica Valencia, Jhesua Cadena, Christian Camilo Maiti, Raktim Datta, Chandreyee Puerto, Gloria Isaza, José Hipólito San Juan, Homero Nagaraja, Valakunja Guzman, Juan David Molecules Article Tuberculosis continues to be a great source of concern in global health because of the large reservoir of humans infected with the bacilli and the appearance of clinical isolates resistant to a wide array of anti-tuberculosis drugs. New drugs with novel mechanisms of action on new targets are urgently required to reduce global tuberculosis burden. Mycobacterium tuberculosis nucleoid associated protein (NAP) HU has been shown to be druggable and essential for the organism’s survival. In this study, four diarylethenes were synthesized using a one-pot decarboxylated Heck-coupling of coumaric acids with iodoanisoles. The prepared compounds 1–4 were tested for their in vitro growth inhibition of M. tuberculosis H37Rv using the spot culture growth inhibition assay, displaying minimum inhibitory concentrations between 9 and 22 µM. Their cytotoxicity against BHK-21 cell line showed half inhibition at concentrations between 98 and 729 µM. The most selective hit (SI = 81), demonstrated inhibition of M. tuberculosis HU protein involved in maintaining bacterial genome architecture. MDPI 2017-07-25 /pmc/articles/PMC6151991/ /pubmed/28757569 http://dx.doi.org/10.3390/molecules22081245 Text en © 2017 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Suarez, María Angélica Valencia, Jhesua Cadena, Christian Camilo Maiti, Raktim Datta, Chandreyee Puerto, Gloria Isaza, José Hipólito San Juan, Homero Nagaraja, Valakunja Guzman, Juan David Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein |
title | Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein |
title_full | Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein |
title_fullStr | Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein |
title_full_unstemmed | Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein |
title_short | Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein |
title_sort | diarylethenes display in vitro anti-tb activity and are efficient hits targeting the mycobacterium tuberculosis hu protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151991/ https://www.ncbi.nlm.nih.gov/pubmed/28757569 http://dx.doi.org/10.3390/molecules22081245 |
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