ArticleChembiochem : a European journal of chemical biology2024
Identification of a 2-Aminobenzimidazole Scaffold that Potentiates Gram-Positive Selective Antibiotics Against Gram-Negative Bacteria.
Article in Chembiochem : a European journal of chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Macrolide antibiotic action, resistance, and tolerance, and approaches to improve their activity against Gram-negative bacteria.The Journal of antibiotics · 2026Review
- Metacycloprodigiosin produced by a high-yieldOrganic & biomolecular chemistry · 2026Article
- Structure-activity relationship and molecular docking analysis of novel arylhydrazones of imidazodiazabicycloalkanones with antibacterial properties.Molecular diversity · 2026Article
- 2‑Aminoimidazole-benzimidazole Conjugates Potentiate the Gram-Positive Selective Antibiotic Clarithromycin againstACS medicinal chemistry letters · 2025Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The development of novel therapeutic approaches is crucial in the fight against multi-drug resistant (MDR) bacteria, particularly gram-negative species. Small molecule adjuvants that enhance the activity of otherwise gram-positive selective antibiotics against gram-negative bacteria have the potential to expand current treatment options. We have previously reported adjuvants based upon a 2-aminoimidazole (2-AI) scaffold that potentiate macrolide antibiotics against several gram-negative pathogens. Herein, we report the discovery and structure-activity relationship (SAR) investigation of an additional class of macrolide adjuvants based upon a 2-aminobenzimidazole (2-ABI) scaffold. The lead compound lowers the minimum inhibitory concentration (MIC) of clarithromycin (CLR) from 512 to 2 μg/mL at 30 μM against Klebsiella pneumoniae 2146, and from 32 to 2 μg/mL at 5 μM, against Acinetobacter baumannii 5075. Preliminary investigation into the mechanism of action suggests that the compounds are binding to lipopolysaccharide (LPS) in K. pneumoniae, and modulating lipooligosaccharide (LOS) biosynthesis, assembly, or transport in A. baumannii.
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Registered trials
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