Design, Synthesis and Pharmacological Evaluation of Some Novel Heterocyclic Antihyperlipidemic Agents

Saraswathy, T (2016) Design, Synthesis and Pharmacological Evaluation of Some Novel Heterocyclic Antihyperlipidemic Agents. Doctoral thesis, College of Nursing, Madurai Medical College, Madurai.


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In-silico approach was used to select thirty molecules which are predicted to be effective against the target enzyme HMG -Co-A and the protein was downloaded from Protein Bank (PDB id-1t02). This was done by molecular docking studies against the target enzyme and the ligands. • In-silico ADME assessment and In-silico toxicity predictions were carried out to find the drug likeness property and toxicity nature of the selected 30 molecules after docking. • 30 molecules which were selected from docking score were synthesized. • The synthesised molecules are 1,2,3 triazole derivatives of Coumarin, Quinoline and Pthalimide. Thirty new molecules comprises of 14 number of 1,2,3 – triazole derivatives of Coumarin (5a-5g and 6a-6g). 14 number of 1,2,3 – triazole derivatives of Quinoline (9a-9g and 10a-10g). 2 number of 1,2,3 – triazole derivatives of Pthalimide (13a-13b). • The thirty synthesised compounds were purified by chromatography using ethyl acetate and hexane (1:2) as eluting agent. • Melting point was determined by open capillary method and are presented uncorrected. All the molecules were characterized by FT-IR,1H-NMR,13C-NMR and Mass spectra. • Based upon the docking score top four molecules were chosen for anti hyperlipidemic activity. (QMB (9b), QEB (10a), QEB (10b) and CEH(6e)). • Anti-hyperlipidemic activity was carried out by feeding high fat diet to 7 groups of six animals each and at the end of nine weeks, animals were sacrificed. • The tissues were taken for in-vivo antioxidant study. • All the synthesized compounds showed increase in HDL level of the animals as compared to the group which was administered with standard drug. • The compound reduced the body weight of the animals which are fed with high fat diet at a lower dose and also decreased the level of LDL in the blood. • The in- vivo antioxidant showed good increase in the levels of Superoxide Dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx) and Glutathione reductase (GR) compared with that of the control group. • The stability of the ligand receptor complexes were analysed by molecular dynamic stimulation. This was performed with the top glide score ligand. The study confirmed that the ligand receptor complex was stable without any notable conformational changes during the simulation run. • At the end of the MD simulation, changes in the position and orientation of ligands in the introduced binding site was observed which indicates the usefulness of the MD simulation for optimization of the ligands into the target binding site. • In the present work, simple and efficient practical methods were adopted for the synthesis of the heterocyclics which resulted from the in-silico and the compunds were obtained in good yield. • The compounds with 1,2,3 triazoles showed good anti-hyperlipidemic activity at lower dose as compared to that of the standard. • The good profile of the molecules with the In-silico toxicity and In-silico ADME properties shows it can be taken for further studies. • The Molecular simulation method also concludes the stability of ligand -receptor is significant for the compound with 1,2,3 triazole containing quinoline nucleus QEP(10b). • The above findings have demonstrated that the compound is possibly a future drug moiety for treating hyperlipidemia.

Item Type: Thesis (Doctoral)
Uncontrolled Keywords: Design, Synthesis, Pharmacological Evaluation, Some Novel Heterocyclic Antihyperlipidemic Agents.
Subjects: PHARMACY > Pharmaceutical Chemistry
Depositing User: Subramani R
Date Deposited: 14 Jan 2020 17:44
Last Modified: 15 Oct 2022 15:00

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