Synthesis, Characterization, Molecular Modelling and Biological Evaluation of Substituted Benzo (h) Chromene-3-Carboxylate Derivatives as a Potential Agent for the Treatment of Hyperlipidemia

Hyperlipidemia is characterized by a rise in high-density lipoproteins and decreases in low-density lipoproteins and triglyceride level in blood serum. Numerous prescription drugs for hyperlipidemia are available, but each has significant side effects. Many works were motivated in this area by the significant pharmacological action of fused chromene. Throughout the present research, new substituted derivatives were synthesized and tested for the anti-hyperlipidemic activity for benzo[h]chromene-3 carboxylate derivatives. Molecules docking showed that compound Vf has greater energy affinity binding values (-12.898 kcal/mol) with 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase enzyme compared with atorvastatin (-11.8605 kcal/mol). All synthesized compounds (Va-l) were able to decreases total cholesterol, low-density lipoproteins and triglycerides and increased high-density lipoproteins and very low-density lipoprotein in hyperlipidemic rats. Compounds Va-l have a good affinity towards 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase enzyme. High yield, good affinity, a nontoxic and low cardiac risk with potential antihyperlipidemic activity make these compounds the possible lead for future research.