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

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.

SUBMITTER: Brown AK

PROVIDER: S-EPMC6412293 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Brown Alistair K AK Aljohani Ahmed K B AKB Gill Jason H JH Steel Patrick G PG Sellars Jonathan D JD

Molecules (Basel, Switzerland) 20190223 4

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 st ...[more]

PMID: 30813427

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Project description:Indole-containing small molecules have been reported to have diverse pharmacological activities. The aromatic heterocyclic scaffold, which resembles various protein structures, has received attention from organic and medicinal chemists. Exploration of indole derivatives in drug discovery has rapidly yielded a vast array of biologically active compounds with broad therapeutic potential. Nature is the major source of indole scaffolds, but various classical and advanced synthesis methods for indoles have also been reported. One-pot synthesis is widely considered an efficient approach in synthetic organic chemistry and has been used to synthesize some indole compounds. The rapid emergence of drug-resistant tuberculosis is a major challenge to be addressed. Identifying novel targets and drug candidates for tuberculosis is therefore crucial. Researchers have extensively explored indole derivatives as potential anti-tubercular agents or drugs. Indole scaffolds containing the novel non-covalent (decaprenylphosphoryl-β-D-ribose2'-epimerase) DprE1 inhibitor 1,4-azaindole is currently in clinical trials to treat Mycobacterium tuberculosis. In addition, DG167 indazole sulfonamide with potent anti-tubercular activity is undergoing early-stage development in preclinical studies. Indole bearing cationic amphiphiles with high chemical diversity have been reported to depolarize and disrupt the mycobacterial membrane. Some indole-based compounds have potential inhibitory activities against distinct anti-tubercular targets, including the inhibition of cell wall synthesis, replication, transcription, and translation, as summarized in the graphical abstract. The success of computer-aided drug design in the fields of cancer and anti-viral drugs has accelerated in silico studies in antibacterial drug development. This review describes the sources of indole scaffolds, the potential for novel indole derivatives to serve as anti-tubercular agents, in silico findings, and proposed actions to facilitate the design of novel compounds with anti-tubercular activity.

Dataset Information

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

Publications

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

Similar Datasets

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