Balakumar, B (2021) Design, Synthesis, Characterization and Biological Evaluation of Some Novel Benzimidazole Schiff Base Derivatives as Antitubercular Agents Targeting Glutamine Synthetase 1. Masters thesis, College of Pharmacy, Madras Medical College, Chennai.
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Abstract
Based on the various medicinal chemistry journals Glutamine synthetase1 was selected as the target for the study. ➢ A database of 500 molecules with high prospects of inhibiting the target Glutamine synthetase was carefully chosen by making changes to the known hit molecules, i.e., Benzimidazole chalcones. ➢ The molecules were subjected to toxicity assessment by OSIRIS® property explorer. ➢ In-silico drug likeness properties of the designed molecules were determined by using the MOLINSPIRATION® software. ➢ 500 molecules were docked against the target protein using AutoDock 4 ®. ➢ Five molecules with good docking score [lower binding energy] and interactions were shortlisted and optimized for the synthesis. ➢ Compounds were synthesized with satisfactory yield and labelled as BK-1, BK-2, BK-3, BK-4 and BK-5. ➢ Purity of the synthesized compounds was ensured by repeated recrystallization and the compounds were evaluated by TLC and Melting point. ➢ The characterization of the synthesized compounds was done using Infra-red spectroscopy, Liquid Chromatography-Mass spectrometric methods [LC-MS] and Nuclear Magnetic Resonance [H1 NMR] spectroscopy methods. ➢ The pure compounds were screened for Anti-mycobacterial activity by in-vitro Microplate Alamar Blue Assay [MABA]. MIC of synthesized compound were found in the range of 50μg/ml 3.12 μg/ml. ➢ Acute oral toxicity study was conducted on albino wistar rats and all the compounds were found to be safe and non-toxic. CONCLUSION: ✓ Novel Benzimidazole chalcone derivatives were found to be capable of inhibiting the target enzyme Glutamine synthetase 1which is essential for the synthesis of mycobacterium cell wall. ✓ The docking score of the designed compound range between -8.56 to -5.87 Kcal/mol. ✓ All the compounds inhibited the Mycobacterium tuberculosis in the range of 3.12μg/ml to 50μg/ml. ✓ The acute toxicity studies revealed that all the compounds are safe and non-toxic. ✓ The MABA test was carried out using H37Rv strain which is non- pathogenic. Hence further studies should be carried out using clinical isolates i.e, Pathogenic strain. ✓ Further structural refinement of the synthesized compounds is expected to yield promising drug candidate against Mycobacterium tuberculosis.
| Item Type: | Thesis (Masters) |
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| Additional Information: | 261915702 |
| Uncontrolled Keywords: | Design, Synthesis, Characterization, Biological Evaluation, Some Novel Benzimidazole Schiff Base Derivatives, Antitubercular Agents, Targeting, Glutamine Synthetase 1. |
| Subjects: | PHARMACY > Pharmaceutical Chemistry |
| Depositing User: | Subramani R |
| Date Deposited: | 02 Nov 2022 17:44 |
| Last Modified: | 03 Nov 2022 14:06 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/20926 |
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