Design, Synthesis, Characterization and Biological Evaluation of Some Novel Aldimines of Benzimidazole as Antitubercular Agents.

Sathya Sukanya, S (2014) Design, Synthesis, Characterization and Biological Evaluation of Some Novel Aldimines of Benzimidazole as Antitubercular Agents. Masters thesis, College of Pharmacy, Madras Medical College, Chennai.

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AIM: The present study of this project is to discover molecules with potential anti-tubercular activity. OBJECTIVE: The compounds are designed and docked against a specific crucial target, Glutamine Synthase 1, which is involved in the cell wall biosynthesis and nitrogen metabolism. The synthesized compounds are expected to act on the same. The plan of work includes: Design of glutamine Synthase 1 inhibitors by docking studies. Insilico Drug Likeness Prediction Insilico Toxicity Assessment Laboratory synthesis of the compounds with top G.Score Characterization of the synthesized compounds by Infrared Spectroscopy 1H Nuclear Magnetic Resonance Spectroscopy Mass Spectroscopy In-vitro anti tubercular activity of synthesized compounds (MABA). Glutamine Synthase I is a vital enzyme present in the cell wall of Mycobacterium tuberculosis H37Rv.It belongs to the Ligase family. This enzyme was chosen as the target for the drug design study after thorough literature review. A database of 100 molecules with potential to inhibit the target (PDB id: 4ACF) was chosen by altering the lead molecule, 6-nitro benzimidazole. The designed molecules were docked against the target chosen using Schrodinger‟s GLIDE® (Grid Based Ligand Docking with Energetics. From among the docked molecules, 5 molecules with good Glide score were chosen for laboratory synthesis. The drug likeness and toxicity prediction was carried out for the filtered 5 compounds in silico. Then further the compounds were synthesized. The reaction conditions were optimized. The compounds were labeled as SSS-HBZ, SSS-DMAB, SSS-CNBZ, SSS- FUR and SSS-PC and synthesized and recrystallised. The purity of the synthesized compounds were evaluated by melting point and TLC and were characterized by Infrared Spectroscopy, Nuclear Magnetic Resonance Spectroscopy and Mass Spectroscopy. The purified compounds were screened for antitubercular activity by invitro Micro Plate Alamar Blue Assay. The Minimum Inhibitory Concentration (MIC) of all the synthesized compounds were at 50 μg /ml except SSS-HBZ which was at 100 μg/ml against the MIC of known TB drugs Pyrazinamide: 3.125 mcg/ml, Ciprofloxacin: 3.125 mcg/ml and Streptomycin 6.25 mcg/ml. CONCLUSION: It is concluded that the synthesized compounds might effectively inhibit the chosen target, Glutamine Synthase 1 which is essential for the growth of the Mycobacterium tuberculosis. Further structural modifications of the synthesized compounds will aid in the development of potential molecules against the pathogen.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Novel Aldimines; Benzimidazole; Antitubercular Agents
Subjects: PHARMACY > Pharmaceutical Chemistry
Depositing User: Ravindran C
Date Deposited: 20 Oct 2017 06:58
Last Modified: 20 Oct 2017 06:58

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