Design, Synthesis, Characterization and Biological Evaluation of Some Novel Pyridine Derivatives as Anti-Tubercular Agents against INHA

Suresh Kumar, S (2018) Design, Synthesis, Characterization and Biological Evaluation of Some Novel Pyridine Derivatives as Anti-Tubercular Agents against INHA. Masters thesis, College of Pharmacy, Madras Medical College, Chennai.


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Inh A(enoyl-ACP reductase) (2h9i) a critical enzyme for the growth of Mycobacterium tuberculosis was chosen for our study after review of literature. • Candidate molecules were designed and docked against 2h9i protein using AUTO DOCK® 1.5.6 software. • 4 Molecules with good Docking score (lower binding energy) and interactions were shortlisted for synthesis. Reaction conditions were optimized. • The selected molecules were subjected to toxicity prediction assessment by OSIRIS® software. • Compounds were synthesized by conventional method and labeled as DCP1, DCP2, DCP3, PIA. Purity of the synthesized compounds was ensured by repeated recrystallisation and purification by column chromatography. Further the compounds were evaluated by TLC and Melting point determination. • The characterization of the synthesized compounds was done using Infra-red, Nuclear Magnetic Resonance (H1 NMR, C13 NMR) and Mass spectroscopic methods (LC-MS,). • The pure compounds were screened for In- Vitro Anti- mycobacterial activity by MicroplateAlamar Blue Assay (MABA). All compounds showed significant antimycobacterium activity. • The synthesized compound DCP1 were active at 1.6μg/ml, which were comparable into the known anti-TB drugs: Pyrazinamide - 3.125μg/ml, Ciprofloxacin - 3.125μg/ml and Streptomycin - 6.25μg/ml. The compounds DCP2 and DCP3 were active at 12.5μg/ml. • The IC50 values synthesized compounds DCP1 and DCP3 were 389.7 μg/ml and 319.3μg/ml respectively. CONCLUSION: Our work concludes that our synthesized molecules are effective in inhibiting enzymeInhA (enoyl-ACP reductase) (2h9i) which is important for the growth of Mycobacterium tuberculosis. • All the 4 compounds gave Docking score between -5 to -8 kcal/mol. This goes to prove that 2h9i is a critical enzyme for anti-mycobacterial lactivity. • The minimum inhibitory concentration of the 4 synthesized compounds against H37RV ranged from 50 to 1.6 μg/ml. • Further structural refinement to the structure of the synthesized compounds is expected to yield promising molecules against the pathogen Mycobacterium tuberculosis.

Item Type: Thesis (Masters)
Additional Information: Reg No: 261615708
Uncontrolled Keywords: Some Novel Pyridine Derivatives ; Anti-Tubercular Agents ; INHA ; Design ; Synthesis ; Characterization ; Biological Evaluation.
Subjects: PHARMACY > Pharmaceutical Chemistry
Depositing User: Subramani R
Date Deposited: 28 Jun 2019 02:43
Last Modified: 28 Jun 2019 02:43

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