title: Old class but new dimethoxy analogue of benzimidazole: a bacterial topoisomerase I inhibitor.
abstract: New antimicrobials are needed to combat drug resistance and have often been equated with the identification and exploitation of novel targets. This study focused on the synthesis of new benzimidazole analogues with improved DNA minor groove-binding affinity and having lower cytotoxicity to mammalian cells as well as selective targeting of bacterial DNA over host DNA. 5-(4-Methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxyphenyl)-5'-benzimidazolyl]benzimidazole (DMA) cleared bacterial infections from mammalian cell culture without apparent cytotoxicity to mammalian cells. Moreover, DMA inhibited microbial topoisomerase over mammalian topoisomerase, with a 50% inhibitory concentration (IC50) value for human topoisomerase I of >54microM compared with an IC50 of <10microM for Escherichia coli topoisomerase I in vitro.
authors.affiliation: Dr B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Bansal
authors.forename: Urmila
authors.initials: U
authors.lastname: Tawar
authors.forename: Manish
authors.initials: M
authors.lastname: Singh
authors.forename: Abbas
authors.initials: A
authors.lastname: Nikravesh
authors.forename: Liam
authors.initials: L
authors.lastname: Good
authors.forename: Vibha
authors.initials: V
authors.lastname: Tandon
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D009457:Neuroglia / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D059004:Topoisomerase I Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D001562:Benzimidazoles; D059004:Topoisomerase I Inhibitors; C031000:benzimidazole