ArticlePloS one2014
A trisubstituted benzimidazole cell division inhibitor with efficacy against Mycobacterium tuberculosis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Microbiological evidence for the trisubstituted benzimidazoles targeting MmpL3 inAntimicrobial agents and chemotherapy · 2025Article
- Overcoming the Prokaryote/Eukaryote Barrier in Tuberculosis Treatment: A Prospect for the Repurposing and Use of Antiparasitic Drugs.Microorganisms · 2021Review
- Impact of FtsZ Inhibition on the Localization of the Penicillin Binding Proteins in Methicillin-Resistant Staphylococcus aureus.Journal of bacteriology · 2021Article
- Structure-Guided Design of a Fluorescent Probe for the Visualization of FtsZ in Clinically Important Gram-Positive and Gram-Negative Bacterial Pathogens.Scientific reports · 2019Article
- Novel T9 loop conformation of filamenting temperature-sensitive mutant Z from Mycobacterium tuberculosis.Acta crystallographica. Section F, Structural biology communications · 2019Article
- Strategic incorporation of fluorine in the drug discovery of new-generation antitubercular agents targeting bacterial cell division protein FtsZ.Journal of fluorine chemistry · 2017Article
- Recent advances in the discovery and development of antibacterial agents targeting the cell-division protein FtsZ.Bioorganic & medicinal chemistry · 2016Review
- Formulation studies of InhA inhibitors and combination therapy to improve efficacy against Mycobacterium tuberculosis.Tuberculosis (Edinburgh, Scotland) · 2016Article
- Synthesis and investigation of novel benzimidazole derivatives as antifungal agents.Bioorganic & medicinal chemistry · 2016Article
- Targeting the Bacterial Division Protein FtsZ.Journal of medicinal chemistry · 2016Review
- Cell division inhibitors with efficacy equivalent to isoniazid in the acute murine Mycobacterium tuberculosis infection model.The Journal of antimicrobial chemotherapy · 2015Article
- Antimicrobial activity of a quinuclidine-based FtsZ inhibitor and its synergistic potential with β-lactam antibiotics.The Journal of antibiotics · 2015Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Trisubstituted benzimidazoles have demonstrated potency against Gram-positive and Gram-negative bacterial pathogens. Previously, a library of novel trisubstituted benzimidazoles was constructed for high throughput screening, and compounds were identified that exhibited potency against M. tuberculosis H37Rv and clinical isolates, and were not toxic to Vero cells. A new series of 2-cyclohexyl-5-acylamino-6-N, N-dimethylaminobenzimidazoles derivatives has been developed based on SAR studies. Screening identified compounds with potency against M. tuberculosis. A lead compound from this series, SB-P17G-A20, was discovered to have an MIC of 0.16 µg/mL and demonstrated efficacy in the TB murine acute model of infection based on the reduction of bacterial load in the lungs and spleen by 1.73 ± 0.24 Log10 CFU and 2.68 ± Log10 CFU, respectively, when delivered at 50 mg/kg by intraperitoneal injection (IP) twice daily (bid). The activity of SB-P17G-A20 was determined to be concentration dependent and to have excellent stability in mouse and human plasma, and liver microsomes. Together, these studies demonstrate that SB-P17G-A20 has potency against M. tuberculosis clinical strains with varying susceptibility and efficacy in animal models of infection, and that trisubstituted benzimidazoles continue to be a platform for the development of novel inhibitors with efficacy.
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