1268487-33-7Relevant articles and documents
Selective Inhibition of Escherichia coli RNA and DNA Topoisomerase i by Hoechst 33258 Derived Mono-and Bisbenzimidazoles
Ranjan, Nihar,Story, Sandra,Fulcrand, Geraldine,Leng, Fenfei,Ahmad, Muzammil,King, Ada,Sur, Souvik,Wang, Weidong,Tse-Dinh, Yuk-Ching,Arya, Dev P.
, p. 4904 - 4922 (2017/06/28)
A series of Hoechst 33258 based mono-and bisbenzimidazoles have been synthesized and their Escherichia coli DNA topoisomerase I inhibition, binding to B-DNA duplex, and antibacterial activity has been evaluated. Bisbenzimidazoles with alkynyl side chains display excellent E. coli DNA topoisomerase I inhibition properties with IC50 values 32 μg/mL). Bisbenzimidazoles showed varied stabilization of B-DNA duplex (1.2?ê'23.4 °C), and cytotoxicity studies show similar variation dependent upon the side chain length. Modeling studies suggest critical interactions between the inhibitor side chain and amino acids of the active site of DNA topoisomerase I.
Synthesis and investigation of novel benzimidazole derivatives as antifungal agents
Chandrika, Nishad Thamban,Shrestha, Sanjib K.,Ngo, Huy X.,Garneau-Tsodikova, Sylvie
, p. 3680 - 3686 (2016/07/20)
The rise and emergence of resistance to antifungal drugs by diverse pathogenic fungal strains have resulted in an increase in demand for new antifungal agents. Various heterocyclic scaffolds with different mechanisms of action against fungi have been investigated in the past. Herein, we report the synthesis and antifungal activities of 18 alkylated mono-, bis-, and trisbenzimidazole derivatives, their toxicities against mammalian cells, as well as their ability to induce reactive oxygen species (ROS) in yeast cells. Many of our bisbenzimidazole compounds exhibited moderate to excellent antifungal activities against all tested fungal strains, with MIC values ranging from 15.6 to 0.975?μg/mL. The fungal activity profiles of our bisbenzimidazoles were found to be dependent on alkyl chain length. Our most potent compounds were found to display equal or superior antifungal activity when compared to the currently used agents amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole against many of the strains tested.
Methods and compositions related to viral inhibition
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, (2015/07/15)
Disclosed herein are compounds, compositions and methods related to viral inhibition. In some forms, the compounds, compositions and methods are related to binding RNA.
Recognition of HIV-TAR RNA using neomycin-benzimidazole conjugates
Ranjan, Nihar,Kumar, Sunil,Watkins, Derrick,Wang, Deyun,Appella, Daniel H.,Arya, Dev P.
, p. 5689 - 5693 (2013/10/01)
Synthesis of a novel class of compounds and their biophysical studies with TAR-RNA are presented. The synthesis of these compounds was achieved by conjugating neomycin, an aminoglycoside, with benzimidazoles modeled from a B-DNA minor groove binder, Hoechst 33258. The neomycin-benzimidazole conjugates have varying linkers that connect the benzimidazole and neomycin units. The linkers of varying length (5-23 atoms) in these conjugates contain one to three triazole units. The UV thermal denaturation experiments showed that the conjugates resulted in greater stabilization of the TAR-RNA than either neomycin or benzimidazole used in the synthesis of conjugates. These results were corroborated by the FID displacement and tat-TAR inhibition assays. The binding of ligands to the TAR-RNA is affected by the length and composition of the linker. Our results show that increasing the number of triazole groups and the linker length in these compounds have diminishing effect on the binding to TAR-RNA. Compounds that have shorter linker length and fewer triazole units in the linker displayed increased affinity towards the TAR RNA.
