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

Brown, Alistair; Aljohani, Ahmed; Gill, Jason; Steel, Patrick; Sellars, Jonathan

doi:10.3390/molecules24040811

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

Brown, Alistair; Aljohani, Ahmed; Gill, Jason; Steel, Patrick; Sellars, Jonathan

Authors

Alistair Brown

Ahmed Aljohani

Jason Gill

Professor Patrick Steel p.g.steel@durham.ac.uk
Professor

Jonathan Sellars

Abstract

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.

Citation

Brown, A., Aljohani, A., Gill, J., Steel, P., & Sellars, J. (2019). Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents. Molecules, 24(4), Article 811. https://doi.org/10.3390/molecules24040811

Journal Article Type	Article
Acceptance Date	Feb 20, 2019
Online Publication Date	Feb 23, 2019
Publication Date	Feb 23, 2019
Deposit Date	Mar 7, 2019
Publicly Available Date	Mar 7, 2019
Journal	Molecules
Publisher	MDPI
Peer Reviewed	Peer Reviewed
Volume	24
Issue	4
Article Number	811
DOI	https://doi.org/10.3390/molecules24040811

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