Design, Synthesis, Characterization and Biological Evalution of Some Novel Heterocyclic Derivatives as Anti - Tubercular Agents

Madhesh, K (2016) Design, Synthesis, Characterization and Biological Evalution of Some Novel Heterocyclic Derivatives as Anti - Tubercular Agents. Masters thesis, College of Pharmacy, Madras Medical College, Chennai.


Download (2MB) | Preview


INTRODUCTION:TUBERCULOSIS Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but TB bacteria can attack any part of the body such as the kidney, spine, and brain. If not treated properly, TB disease can be fatal. (1) Consumption, phthisis, scrofula, Pott’s disease and the white plague are all terms used to refer to tuberculosis throughout history. (2) Spreadability of TB (1) TB is spread through the air from one person to another. The TB bacteria are put into the air when a person with TB disease of the lungs or throat coughs, sneezes, speaks, or sings. People nearby may breathe in these bacteria and become infected. TB is NOT spread by Shaking someone's hand, Sharing food or drink, Touching bed linens or toilet seats, Sharing toothbrushes, Kissing AIM:To develop novel Anti-tubercular molecules, which inhibit Cyclopropane mycolic acid synthase-2 (cmaA-2).OBJECTIVE:The Objective of the project is to Design, Synthesis, and Characterize and biologically evaluates some novel Anti-tubercular molecules.SUMMARY:Cyclopropane Mycolic acid Synthase-2 (1KPI) a critical enzyme for the growth of Mycobacterium tuberculosis was chosen for our study after review of literature. 1. A database of 200 molecules with high prospect of inhibiting the target 1KPI were carefully chosen by making changes to the known hit molecules, here the Imidazole nucleus and Benzimidazole nucleus. 2. Candidate molecules were designed and docked against 1KPI protein using Argus lab 4.0.1 software. 3. Five molecules with good Docking score (lower binding energy) and interactions were shortlisted for synthesis. Reaction conditions were optimized. 4. The selected molecules were subjected to toxicity prediction assessment by OSIRIS software. The results are colour coded as green colour which confirms the drug likeness. 5. The molecules were labelled as M1, M2, M3, M7 and M11 synthesized with satisfactory yield. 6. Purity of the synthesized compounds was ensured by repeated recrystallization. Further the compounds were evaluated by TLC and Melting point determination. 7. The characterization of the synthesized compounds was done using Infra-red, Nuclear Magnetic Resonance (H1 NMR) and Mass spectroscopic methods (LC-MS, GC-MS). 8. The final pure compounds were screened for Anti- mycobacterial activity by in vitro method called Microplate Alamar Blue Assay (MABA).CONCLUSION:My work concludes that my synthesized molecules are slightly effective in inhibiting enzyme Cyclopropane Mycolic acid Synthase-2 (1KPI), which is important for the growth of Mycobacterium tuberculosis Cell wall. Among the four other enzymes the cyclopropane mycolic acid synthase 2 was the best enzyme for inhibiting Mycobacterium tuberculosis. Streptomycin gave Docking score of -7.4 for 1KPI and Ciprofloxacin gave Docking score of -5.9 for 1KPI. There is correlation between the score and activities of all the 5 compounds which were tested and compared with the standard drugs. This goes to prove that 1KPI is a critical enzyme for anti-mycobacterial activity. The Minimum inhibitory concentration of the 5 synthesized compounds against H37RV ranged from 50 μg/ml to >100 μg/ml which is compared to that of the certain known Anti-TB agents Pyrazinamide- 3.125μg/ml, Ciprofloxacin- 3.125μg/ml and Streptomycin- 6.25μg/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.261415712
Uncontrolled Keywords: Design; Synthesis ; Characterization ; Biological Evalution ; Novel Heterocyclic Derivatives ; Anti - Tubercular Agents.
Subjects: PHARMACY > Pharmaceutical Chemistry
Depositing User: Ravindran C
Date Deposited: 16 Mar 2018 09:58
Last Modified: 21 Mar 2018 11:54

Actions (login required)

View Item View Item