Identification and development of oxoquinazoline derivatives as novel mycobacterial inhibitors targeting cell wall synthesis enzyme
2018
Prasanthi Malapati | Krishna Siva Vagolu | Dhramarajan Sriram
Background: Tuberculosis (TB) still remains the leading cause of death worldwide and was unanswered till date. Available treatment strategies have many drawbacks such as longer treatment period, side effects, and drug interactions, which result in patient noncompliance. In the present work, we thrived to develop inhibitors against unexplored key target glutamate racemase. Methods: Lead was identified from in-house database using differential scanning fluorimetry, inhibitors were developed by lead derivatization technique and evaluated them by various biological assays. Results: In oxoquinazoline series, compounds 18 (10.1 ± 0.62 μM) and 22 (5.23 ± 0.34 μM) were found to be the most promising potent inhibitors among all. These compounds also showed their inhibition on replicating and nonreplicating bacteria. Conclusion: Our attempt to develop the potent novel inhibitors against Mycobacterium tuberculosis resulted in developing few promising inhibitors, yet these compounds need further studies to answer all questions in drug discovery. Further optimization of compounds can result in still better compounds for treating TB.
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