Abstract
Bacteria are rapidly evolving to be resistant to
currently available antibiotics. In our fight against disease-causing
pathogenic bacteria, it is crucial to synthesize compounds that can selectively
work against bacteria while avoiding antibiotic resistance mechanisms. Enzyme
inhibitors that selectively target bacterial enzymes, such as DNA topoisomerases (Topos),
over their human equivalent offer a unique benefit in that regard. DNA Topos are enzymes responsible for the relaxation of (+) and (-) supercoiled (sc) DNA and the resolution of DNA knots and catenanes during essential biological processes, such as DNA replication, transcription, recombination, and maintenance of chromosome structure. DNA Topos that control DNA topology inside cells are, thus, important targets for certain antibiotics and anticancer drugs.FIU scientists have synthesized Hoechst 33258 based bisbenzimidazoles containing a
terminal hydrophobic group.
These bisbenzimidazoles display topoisomerase I inhibition that is much better
than Hoechst 33342 or Hoechst 33258, with IC50 values in the range
of 2.47-6.63 μM. These compounds also display selective inhibition of E. coli topoisomerase I over DNA gyrase, human topoisomerases I and II, and effectively
inhibit bacterial growth.
Benefit
Effective and selective inhibition of E. coli topoisomerase I over DNA gyrase, human topoisomerase I and IIAvoids antibacterial resistance mechanisms
Market Application
The compounds can be used as antibacterial agents while avoiding problems associated with drug resistance in bacteria
Publications
Ranjan et al. Med. Chem. Commun.,
2014, 5, 816-825
Brochure
