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Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents

Discovery and development of new therapeutic options for the treatment of Mycobacterium tuberculosis (Mtb) infection are desperately needed to tackle the continuing global burden of this disease and the efficacy and cost limitations associated with current medicines. Herein, we report the synthesis...

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Autores principales: Brown, Alistair K., Aljohani, Ahmed K. B., Gill, Jason H., Steel, Patrick G., Sellars, Jonathan D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412293/
https://www.ncbi.nlm.nih.gov/pubmed/30813427
http://dx.doi.org/10.3390/molecules24040811
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author Brown, Alistair K.
Aljohani, Ahmed K. B.
Gill, Jason H.
Steel, Patrick G.
Sellars, Jonathan D.
author_facet Brown, Alistair K.
Aljohani, Ahmed K. B.
Gill, Jason H.
Steel, Patrick G.
Sellars, Jonathan D.
author_sort Brown, Alistair K.
collection PubMed
description Discovery and development of new therapeutic options for the treatment of Mycobacterium tuberculosis (Mtb) infection are desperately needed to tackle the continuing global burden of this disease and the efficacy and cost limitations associated with current medicines. Herein, we report the synthesis of a series of novel benzoxa-[2,1,3]-diazole substituted amino acid hydrazides in a two-step synthesis and evaluate their inhibitory activity against Mtb and selected bacterial strains of clinical importance utilising an end point-determined REMA assay. Alongside this, their potential for undesired cytotoxicity against mammalian cells was assessed employing standard MTT assay methodologies. It has been demonstrated using modification at three sites (the hydrazine, amino acid, and the benzodiazole) it is possible to change both the antibacterial activity and cytotoxicity of these molecules whilst not affecting their microbial selectivity, making them attractive architectures for further exploitation as novel antibacterial agents.
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spelling pubmed-64122932019-04-09 Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents Brown, Alistair K. Aljohani, Ahmed K. B. Gill, Jason H. Steel, Patrick G. Sellars, Jonathan D. Molecules Article Discovery and development of new therapeutic options for the treatment of Mycobacterium tuberculosis (Mtb) infection are desperately needed to tackle the continuing global burden of this disease and the efficacy and cost limitations associated with current medicines. Herein, we report the synthesis of a series of novel benzoxa-[2,1,3]-diazole substituted amino acid hydrazides in a two-step synthesis and evaluate their inhibitory activity against Mtb and selected bacterial strains of clinical importance utilising an end point-determined REMA assay. Alongside this, their potential for undesired cytotoxicity against mammalian cells was assessed employing standard MTT assay methodologies. It has been demonstrated using modification at three sites (the hydrazine, amino acid, and the benzodiazole) it is possible to change both the antibacterial activity and cytotoxicity of these molecules whilst not affecting their microbial selectivity, making them attractive architectures for further exploitation as novel antibacterial agents. MDPI 2019-02-23 /pmc/articles/PMC6412293/ /pubmed/30813427 http://dx.doi.org/10.3390/molecules24040811 Text en © 2019 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
Brown, Alistair K.
Aljohani, Ahmed K. B.
Gill, Jason H.
Steel, Patrick G.
Sellars, Jonathan D.
Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents
title Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents
title_full Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents
title_fullStr Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents
title_full_unstemmed Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents
title_short Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents
title_sort identification of novel benzoxa-[2,1,3]-diazole substituted amino acid hydrazides as potential anti-tubercular agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412293/
https://www.ncbi.nlm.nih.gov/pubmed/30813427
http://dx.doi.org/10.3390/molecules24040811
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