Meenakumari, V (2019) Design, Synthesis, Characterization and Biological Evaluation of Some Novel Benzothiazole Derivatives as Anti Tubercular Agents Targeting Glutamine Synthetase 1. Masters thesis, College of Pharmacy, Madras Medical College, Chennai.
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Abstract
Glutamine synthetase 1 is a vital enzyme present in the cell wall of Mycobacterium tuberculosis H37Rv belongs to the Ligase family was chosen after the review of literature. Docking of the 3D structures of these 100 entities against the 3D structure of Glutamine Synthetase gave an insight about the energetic (molecular docking) by using AUTODOCK® TOOLS 1.5.6 software. Of these 100 structures, only 5 structures which showed minimum binding energy were chosen for synthesis (around -6.5 to -9.5 kcal/mol). The reaction conditions were optimized. The compounds were labeled as MK 1, MK 3, MK 5, MK 9 and MK 10. These compounds were synthesized and recrystallized. They exhibited the better docking score than the standard Anti-TB drugs like Pyrazinamide -4.69 kcal/mol, Ciprofloxacin -6.45 kcal/mol by using AUTODOCK® TOOLS Software. Toxicity risk assessment prediction was done for all the 5 compounds by OSIRIS® property explorer which is available online. The results are colour coded as green colour, which predict the drug likeness. In silico drug likeness properties were determined by using Molinspiration® Cheminformatics software. CHARACTERISATION The purity of the synthesized compounds were confirmed by TLC and melting point and then characterized by IR, 1H NMR and LC-MS. ANTI-TUBERCULAR ACTIVITY The pure compounds were screened for in-vitro Antitubercular activity by Microplate Alamar Blue Assay method. The synthesized compounds showed sensitivity (Minimum Inhibitory Concentration) in the range between 100-6.25μg/ml. The standard drugs Pyrazinamide, Ciprofloxacin and Streptomycin shows anti-mycobacterial activity at 3.125μg/ml, 3.125μg/ml and 6.25μg/ml concentration respectively. MK 9 was found to be as sensitive as streptomycin (6.25 μg/ml) and Other compounds found to have less activity when compared to the standard drugs. The synthesized compounds showed better docking score than Pyrazinamide, Ciprofloxacin. CONCLUSION It concludes that the synthesized compounds might effectively inhibit the chosen target Glutamine Synthetase 1 which is essential for the Mycobacterial Tuberculosis. Further structural modifications of the synthesized compounds will aid in the developments of potential molecule against the tuberculosis pathogen.
| Item Type: | Thesis (Masters) |
|---|---|
| Additional Information: | 261715705 |
| Uncontrolled Keywords: | Design, Synthesis, Characterization, Biological Evaluation, Benzothiazole Derivatives, Anti Tubercular Agents, Glutamine Synthetase 1 |
| Subjects: | PHARMACY > Pharmaceutical Chemistry |
| Depositing User: | Ramakrishnan J |
| Date Deposited: | 11 May 2022 08:58 |
| Last Modified: | 11 May 2022 08:58 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/20016 |
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