Old class but new dimethoxy analogue of benzimidazole: a bacterial topoisomerase I inhibitor.
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.
Bansal
Sandhya
S
Dr B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.
Tawar
Urmila
U
Singh
Manish
M
Nikravesh
Abbas
A
Good
Liam
L
Tandon
Vibha
V
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
D000900:Anti-Bacterial Agents; D001562:Benzimidazoles; D059004:Topoisomerase I Inhibitors; C031000:benzimidazole