Design Synthesis and Pharmacological Evaluation of Some Novel Heterocyclic Antihyperlipidemic Agents

Abstract

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 newlineo 14 number of 1,2,3 triazole derivatives of Coumarin (5a-5g and 6a-6g). newlineo 14 number of 1,2,3 triazole derivatives of Quinoline (9a-9g and 10a-10g). newlineo 2 number of 1,2,3 triazole derivatives of Pthalimide (13a-13b). newlineThe 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. 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 compounds were obtained in good yield. newlineAnti-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. 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 good profile of the molecules with the In-silico toxicity and In-silico ADME properties shows it can be taken for further studies. The above findings have demonstrated that the compound is possibly a future drug moiety for treating hyperlipidemia.