Background: Tuberculosis is well-known airborne disease caused by Mycobacterium tuberculosis. Available treatment regimen was unsuccessful in eradicating the deaths caused by the disease worldwide. Owing to the drawbacks such as prolonged treatment period, side effects, and drug tolerance, there resulted in patient noncompliance. In the current study, we attempted to develop inhibitors against unexplored key target glutamate racemase.
Methods: Lead identification was done using thermal shift assay from in-house library; inhibitors were developed by lead derivatization technique and evaluated using various biological assays.
Results: In indazole series, compounds 11 (6.32 ± 0.35 μM) and 22 (6.11 ± 0.51 μM) were found to be most promising potent inhibitors among all. These compounds also showed their inhibition on replicating and nonreplicating bacteria.
Conclusion: We have developed the novel inhibitors against M. tuberculosis capable of inhibiting active and dormant bacteria, further optimization of inhibitor derivatives can results in better compounds for eradicating tuberculosis.
Keywords: Biofilm; cell wall synthesis; indazole; thermal shift assay; tuberculosis.