Skip to content
2000
Volume 16, Issue 2
  • ISSN: 2211-3525
  • E-ISSN: 2211-3533

Abstract

Tuberculosis, an ancient infectious disease caused by Mycobacterium tuberculosis, ranks as one of the top ten killers worldwide. The limited number of validated targets and scarce therapeutic options demand that renewed efforts should be made to identify tuberculosis drugs with novel mechanisms of action. To this end, mycobacterial DNA might represent a potential target for the development of effective anti-tubercular compounds. In particular, the minor groove of DNA offers an important recognition site for small-molecules that can be programmed to bind to this region in a sequence-selective manner to disrupt mycobacterial transcription factors activity and ultimately cause bacterial cell death. This review describes the structural features of the DNA-minor groove, the requirements for small molecules to bind to this site and the remarkable biophysical and antibacterial properties of DNA-minor groove binding agents, including netropsin, distamycin and their poly-heterocyclic analogues, diamidines, benzimidazole-containing molecules, duocarmycins and pyrrolo[2,1-c][1,4]benzodiazepines (PBDs). Furthermore, the ability of selected heterocyclic-polyamides and PBDs to significantly inhibit the growth of pathogenic, slow-growing M. tuberculosis and other non-pathogenic mycobacterial strains is highlighted. In summary, DNA-minor groove binding agents may serve as molecular scaffolds for the design of highly efficient probes to treat M. tuberculosis infections.

Loading

Article metrics loading...

/content/journals/aia/10.2174/2211352516666180612080830
2018-08-01
2025-07-09
Loading full text...

Full text loading...

/content/journals/aia/10.2174/2211352516666180612080830
Loading
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test