Sangeetha, V (2021) Design, Synthesis, Characterization and Biological Evaluation of Novel Benzimidazole Chalcone 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 druglikeness 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 VS-1, VS-2, VS-3, VS-4 and VS-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 100μg/ml – 6.25μg/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 designed compound ranges between -8.53 to -5.66 Kj/mol. There is no significant correlation between the docking score and activity of the compound. • All the compounds inhibited the Mycobacterium tuberculosis at the range of 6.25μg/ml to 100μg/ml. • The acute toxicity studies revealed that all the compounds found to be safe and non- toxic. • The MABA test is carried out using H37Rv strain which is non- pathogenic. Hence further studied 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: | 261915708 |
| Uncontrolled Keywords: | Design, Synthesis, Characterization, Biological Evaluation, Novel Benzimidazole Chalcone Derivatives, Antitubercular Agents, Targeting, Glutamine Synthetase 1. |
| Subjects: | PHARMACY > Pharmaceutical Chemistry |
| Depositing User: | Subramani R |
| Date Deposited: | 02 Nov 2022 17:54 |
| Last Modified: | 03 Nov 2022 14:33 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/20932 |
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