Targeting Mycobacterium tuberculosis Topoisomerase I by Small-Molecule Inhibitors

  • Adwait Anand Godbole, Wareed Ahmed, Rajeshwari Subray Bhat, Erin K. Bradley, Sean Ekins, Valakunja Nagaraja
  • Antimicrobial Agents and Chemotherapy, December 2014, ASM Journals
  • DOI: 10.1128/aac.04516-14

Topo I inhibitors for TB

What is it about?

We used a homology model of Mycobacterium tuberculosis topoisomerase I and docked approved drugs. We identified two novel inhibitors in vitro, imipramine and norclomipramine. The binding of these molecules was characterized through extensive experiments. We propose they bind near the metal binding site of the enzyme

Why is it important?

Small molecule inhibitors of Mtb Topo I had not previously been identified. By finding known drugs it has stimulated the search for similar molecules.

Perspectives

Dr Sean Ekins
Collaborations in Chemistry

This is the second paper on the topic to identify inhibitors with different mechanisms.

Read Publication

http://dx.doi.org/10.1128/aac.04516-14

The following have contributed to this page: Dr Sean Ekins