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.
References
Dec 16, 1983·Journal of Immunological Methods·T Mosmann
Jul 18, 2002·Antimicrobial Agents and Chemotherapy·Juan-Carlos PalominoFrançoise Portaels
May 13, 2005·The Journal of Biological Chemistry·Giorgio RicciAnna Maria Caccuri
Sep 10, 2008·Journal of Medicinal Chemistry·Yoonsang ChoJames C Sacchettini
Oct 16, 2008·Journal of Medicinal Chemistry·Sandro CosconatiArthur J Olson
Sep 30, 2014·Current Topics in Medicinal Chemistry·Rahul V PatelSe Won Park
May 20, 2015·Antimicrobial Agents and Chemotherapy·Benoit Lechartier, Stewart T Cole
Nov 13, 2015·The New England Journal of Medicine·Barbara RiveraWilliam D Foulkes
Feb 26, 2016·Journal of Medicinal Chemistry·Sanjib BhaktaDaniele Castagnolo
Oct 26, 2016·PLoS Medicine·Rein M G J Houben, Peter J Dodd
Jan 1, 2017·European Journal of Medicinal Chemistry·Nicolò ScalacciDaniele Castagnolo
Jan 20, 2017·The Lancet Infectious Diseases·Martin J BoereeUNKNOWN PanACEA consortium
Apr 10, 2017·European Journal of Medicinal Chemistry·Yuan-Qiang HuXiang Wu
Mar 10, 2018·Future Microbiology·Anthony L ByrneBen J Marais
Mar 25, 2018·Scientific Reports·Rafael BaptistaLuis A J Mur