Ayyamperumal, E (2018) Design, Synthesis, Characterization and Biological Evaluation of Some Novel Thiadiazole (Schiff’s Base) Derivatives as Antitubercular Agents against Glutamine Synthetase I. Masters thesis, College of Pharmacy, Madras Medical College, Chennai.
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Abstract
Glutamine synthetase I is a vital enzyme present in the cell wall of Mycobacterium tuberculosis H37Rv. It belongs to the Ligase family. • A database of 200 molecules with high prospects of inhibiting the target Glutamine synthetase I were carefully chosen by making changes to the known hit molecules, here the thiadiazole nucleus was chosen. • The designed molecules were docked against the target chosen using AutoDock 4®. • Five molecules with good docking score [lower binding energy] and interactions were shortlisted for synthesis. • The selected molecules were subjected to toxicity prediction assessment by OSIRIS® property explorer developed by Acetilon Pharmaceuticals limited which is available online. The results are color coded as green color which predicts the drug likeness and possibly better activity. • The reaction condition were optimized, synthesized and labelled as BOB, CIN, NIB, OHB, PHB. • The characterization of the synthesized compounds was done using TLC, Melting point Infra-red, Mass spectrometric methods [LC-MS] and Nuclear Magnetic Resonance [H1 NMR] spectroscopy methods. • All the Synthesized compounds exhibited molecular ion peak (M+) of varying intensities. • The final pure compounds were screened for Anti-mycobacterial activity by in vitro method called Microplate Alamar Blue Assay [MABA]. • The synthesized compounds showed sensitivity [Minimum inhibitory concentration] at 3.125mcg/ml. The standard drugs Pyrazinamide, Ciprofloxacin and Streptomycin exhibited anti-mycobacterial activity at 3.125 mcg/ml, 3.125 mcg/ml and 6.25 mcg/ml concentrations respectively. This indicates that the synthesized compounds are as Potent as the standard drugs. • Based on the MABA report, Acute Oral Toxicity study were performed and observed that the administration of the synthesized molecules by oral route upto 2000mg/kg/b.w is safe. • The selected compounds showed IC50 Values of 121.5, 201.9, 472.9, 456.2 μg/ml respectively for BOB, NIB, OHB, PHB. Rifampicin showed IC50 value of 113 μg/ml. As compared with standard drug the synthesized molecules were found to be more cytotoxic. CONCLUSION: It is concluded that the synthesized compounds might effectively inhibit the chosen target Glutamine Synthetase I which is essential for the Mycobacterial tuberculosis. Further structural modifications of the synthesized compounds will aid in the development of potential molecule against the pathogen.
| Item Type: | Thesis (Masters) |
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| Additional Information: | Reg. No. 261615702 |
| Uncontrolled Keywords: | Some Novel Thiadiazole ; Schiff’s Base ; Derivatives ; Antitubercular Agents ; Glutamine Synthetase I ; Design ; Synthesis ; Characterization ; Biological Evaluation. |
| Subjects: | PHARMACY > Pharmaceutical Chemistry |
| Depositing User: | Subramani R |
| Date Deposited: | 28 Jun 2019 03:38 |
| Last Modified: | 28 Jun 2019 03:38 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/10639 |
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