Benzimidazole-based compounds kill Mycobacterium tuberculosis

Gong, Yaling; Karakaya, Selin Somersan; Guo, Xiaoyong; Zheng, Purong; Gold, Ben; Ma, Yao; Little, David; Roberts, Julia; Warrier, Thulasi; Jiang, Xiuju; Pingle, Maneesh; Nathan, Carl; Liu, Gang

doi:10.1016/j.ejmech.2014.01.039

Cited by 47 publications

(24 citation statements)

References 24 publications

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“…Subunit A of VirB8sp structure (PDB http://www.rcsb.org/pdb/search/structidSearch.do?structureId=2BHM ) and VirB8sp M102R (PDB http://www.rcsb.org/pdb/search/structidSearch.do?structureId=5JBS) were used for docking analyses. Docking simulations were conducted using AutodockTools software . Polar hydrogen atoms were added to the protein structures and Gaisteger charges were calculated for each atom.…”

Section: Methodsmentioning

confidence: 99%

Monomer‐to‐dimer transition of Brucella suis type IV secretion system component VirB8 induces conformational changes

et al. 2017

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Section: Methodsmentioning

confidence: 99%

Monomer‐to‐dimer transition of Brucella suis type IV secretion system component VirB8 induces conformational changes

et al. 2017

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“…In the M. tuberculosis phenotypic screen performed by Ananthan et al, 88 compounds with the phenoxyalkylimidazole core were tested, PAB being the most potent active identified in this series, and the only compound in that study with benzimidazole substituted for the imidazole (35). There have since been reports of benzimidazoles having activity against M. tuberculosis (40, 41). We investigated this series and confirmed its potent activity and selectivity (42).…”

Section: Discussionmentioning

confidence: 99%

A high-throughput whole cell screen to identify inhibitors of Mycobacterium tuberculosis

Ollinger

Kumar

Roberts

et al. 2018

Preprint

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Tuberculosis is a disease of global importance for which novel drugs are urgently required. We developed a whole-cell phenotypic screen which can be used to identify inhibitors of Mycobacterium tuberculosis growth. We used recombinant strains of virulent M. tuberculosis which express far-red fluorescent reporters and used fluorescence to monitor growth in vitro. We optimized our high throughput assays using both 96-well and 384-well plates; both formats gave assays which met stringent reproducibility and robustness tests. We screened a compound set of 1105 chemically diverse compounds previously shown to be active against M. tuberculosis and identified primary hits which showed ≥ 90% growth inhibition. We ranked hits and identified three chemical classes of interest – the phenoxyalkylbenzamidazoles, the benzothiophene 1–1 dioxides, and the piperidinamines. These new compound classes may serve as starting points for the development of new series of inhibitors that prevent the growth of M. tuberculosis. This assay can be used for further screening, or could easily be adapted to other strains of M. tuberculosis.

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“…Gong et al. upon evaluating benzimidazole‐based compounds identified compound 15 that potently killed replicating M. tuberculosis (MIC 90 ≤0.049 μg/mL), although it lacked nonreplicating activity when assessed by Colony forming units (CFU) assay . Compound 16 synthesized by Gobis and co‐workers exhibited selective activity against M. tuberculosis with MIC value of 0.75 μg/mL, and low cytotoxic effect on the proliferation of eukaryotic LLC‐PK1 pig kidney epithelial cell line .…”

Section: Benzimidazolesmentioning

confidence: 99%

New structural classes of antituberculosis agents

Kumar

Patel

Jain

2017

Medicinal Research Reviews

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Tuberculosis (TB), one of the deadliest diseases is shattering the health and socioeconomic status of the society. The emergence of multidrug resistant (MDR) and extremely drug resistant (XDR) strains has provided unprecedented lethal character to TB. The development of MDR and XDR strains of TB results in more deaths, longer duration of therapy, and appearance of the disease in the immunocompromised patients. Because of the development of rapid resistance by Mycobacterium tuberculosis, researchers are confronted with serious challenges in combating TB. For instance, the need for potency and specificity in therapeutic agents approaching clinics, and the increasing demand of low toxicity due to long duration of treatment. Recently, it is proposed that such challenges could be addressed by a shift from contemporary or known classes of drugs to new scaffold-containing or entirely new structural classes of drugs that possibly act on the previously unknown targets, resulting in possibly less instances of resistance development. The exploitation of advances made in the biology of TB in the last and present decades have created opportunities to discover a large number of new structural classes that specifically targets TB by molecular mechanism of action(s) unknown earlier. We have earlier reviewed new structural classes of anti-TB agents up to year 2005. This review covers literature reports of the subsequent 10 years on the discovery of new structural classes of synthetic anti-TB agents. Due to the availability of large number of research reports, we have divided new compounds in 38 structural classes, 368 structures, and 307 references.

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Benzimidazole-based compounds kill Mycobacterium tuberculosis

Cited by 47 publications

References 24 publications

Monomer‐to‐dimer transition of Brucella suis type IV secretion system component VirB8 induces conformational changes

Monomer‐to‐dimer transition of Brucella suis type IV secretion system component VirB8 induces conformational changes

A high-throughput whole cell screen to identify inhibitors of Mycobacterium tuberculosis

New structural classes of antituberculosis agents

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