Final Report

1. Project objective

The objective of this project is to screen a library of compounds offered by Astellas Pharma Inc., to identify potential hits for the activity against Mycobacterium tuberculosis (Mtb), the causative agent of TB.    

2. Project design

The design of the project involved screening a collection of synthetic compounds for their ability to inhibit the growth of Mtb. They were tested under two separate conditions to explore the compounds’ ability to inhibit Mtb under replicating and non-replicating growth conditions.            

3. Results, lessons learned

Two series of compounds were identified as potential hits having reasonable in vitro activity against Mtb. They were not designed as antibacterial agents and their chemical structures had not been published in the literature to have activity against Mtb. Additional analogues were synthesized to expand the structure-activity relationships. In vitro ADMET properties were examined on selected analogues and the data suggest they can be potential leads for novel TB drugs. A Hit-to-Lead proposal was prepared and submitted to GHIT. We confirmed that it is possible to identify potential hits against Mtb from non-antibacterial therapeutic areas.