2. Academic Validation
  3. Selective Inhibition of Bacterial Topoisomerase I by alkynyl-bisbenzimidazoles

Selective Inhibition of Bacterial Topoisomerase I by alkynyl-bisbenzimidazoles

  • Medchemcomm. 2014 Jun 1;5(6):816-825. doi: 10.1039/C4MD00140K.
Nihar Ranjan 1,  Geraldine Fulcrand 2,  Ada King 3,  Joseph Brown 4,  Xiuping Jiang 4,  Fenfei Leng 2,  Dev P Arya 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Clemson University, Clemson, South Carolina, Unite States 29634.
  • 2 Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199 (Unite States).
  • 3 NUBAD, LLC, 900 B West Faris Road, Greenville, South Carolina 29605.
  • 4 Department of Biological Sciences, Clemson University, Clemson, South Carolina 29634.
  • 5 Department of Chemistry, Clemson University, Clemson, South Carolina, Unite States 29634 ; NUBAD, LLC, 900 B West Faris Road, Greenville, South Carolina 29605.
PMID: 25083189 DOI: 10.1039/C4MD00140K
Abstract

Hoechst dyes are well known DNA Binders that non-selectively inhibit the function of mammalian Topoisomerase I and II. Herein, we show that Hoechst 33258 based bisbenzimidazoles (DPA 151-154), containing a terminal alkyne, are effective and selective inhibitors of E. coli. Topoisomerase I. These bisbenzimidazoles displayed Topoisomerase I inhibition much better than Hoechst 33342 or Hoechst 33258 with IC50 values in the range of 2.47-6.63 μM. Bisbenzimidazoles DPA 151-154 also display selective inhibition of E. coli. Topoisomerase I over DNA gyrase and Human topoisomerases I and II, and effectively inhibit Bacterial growth.

Figures