ArticleThe Journal of antimicrobial chemotherapy2012
3,4-dimethoxyphenyl bis-benzimidazole, a novel DNA topoisomerase inhibitor that preferentially targets Escherichia coli topoisomerase I.
Article in The Journal of antimicrobial chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 38 citations in OpenAlex.
- Search for Specific Inhibitors Targeting Type IA Topoisomerases.Journal of molecular biology · 2026Review
- Adaptive laboratory-evolved MRSA with PPEF manifests cross-susceptibility to oxacillin and hypersensitivity to ciprofloxacin.Microbiology spectrum · 2025Article
- Unraveling topoisomerase IA gate dynamics in presence of PPEF and its preclinical evaluation against multidrug-resistant pathogens.Communications biology · 2023Article
- Ruthenium Complexes with 2-Pyridin-2-yl-1International journal of molecular sciences · 2021Article
- 1,3,4-OxadiazoleMolecules (Basel, Switzerland) · 2021Article
- Type IA Topoisomerases as Targets for Infectious Disease Treatments.Microorganisms · 2021Review
- Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand.Journal of inorganic biochemistry · 2020Article
- Discovery of novel bacterial topoisomerase I inhibitors by use of in silico docking and in vitro assays.Scientific reports · 2018Article
- Selective Inhibition of Escherichia coli RNA and DNA Topoisomerase I by Hoechst 33258 Derived Mono- and Bisbenzimidazoles.Journal of medicinal chemistry · 2017Article
- Synergistic efficacy of Bisbenzimidazole and Carbonyl Cyanide 3-Chlorophenylhydrazone combination against MDR bacterial strains.Scientific reports · 2017Article
- Small-Molecule Inhibitors Targeting Topoisomerase I as Novel Antituberculosis Agents.Antimicrobial agents and chemotherapy · 2016Article
- An endogenous protein inhibitor, YjhX (TopAI), for topoisomerase I from Escherichia coli.Nucleic acids research · 2015Article
- Targeting bacterial topoisomerase I to meet the challenge of finding new antibiotics.Future medicinal chemistry · 2015Review
- DNA Topoisomerases.EcoSal Plus · 2015Review
- Article
- Identification of anziaic acid, a lichen depside from Hypotrachyna sp., as a new topoisomerase poison inhibitor.PloS one · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesAntibiotic resistance in bacterial pathogens is a serious clinical problem. Novel targets are needed to combat increasing drug resistance in Escherichia coli. Our objective is to demonstrate that 2-(3,4-dimethoxyphenyl)-5-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2yl]-1H-benzimidazole (DMA) inhibits E. coli DNA topoisomerase I more strongly than human topoisomerase I. In addition, DMA is non-toxic to mammalian cells at antibiotic dosage level.
methodsIn the present study, we have established DMA as an antibacterial compound by determining MICs, post-antibiotic effects (PAEs) and MBCs for different standard as well as clinical strains of E. coli. We have described the differential catalytic inhibitory mechanism of bis-benzimidazole, DMA, for human and E. coli topoisomerase I and topoisomerase II by performing different assays, including relaxation assays, cleavage-religation assays, DNA unwinding assays, ethidium bromide displacement assays, decatenation assays and DNA gyrase supercoiling assays.
resultsDMA significantly inhibited bacterial growth at a very low concentration, but did not affect human cell viability at higher concentrations. Activity assays showed that it preferentially targeted E. coli topoisomerase I over human topoisomerase I, topoisomerase II and gyrase. Cleavage-religation assays confirmed DMA as a poison inhibitor of E. coli topoisomerase I. This study illuminates new properties of DMA, which may be further modified to develop an efficient topoisomerase inhibitor that is selective towards bacterial topoisomerase I.
conclusionsThis is the first report of a bis-benzimidazole acting as an E. coli topoisomerase I inhibitor. DMA is a safe, non-cytotoxic molecule to human cells at concentrations that are needed for antibacterial activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.