Antihyperlipidemic studies of newly synthesized phenolic derivatives: in silico and in vivo approaches

Background: Hyperlipidemia is a worth-mentioning risk factor in quickly expanding cardiovascular diseases, including myocardial infarction and, furthermore, in stroke. Methods: The present work describes the synthesis of phenolic derivatives 4a-e and 6a-c with the aim of developing antihyperlipidemic agents. The structures of the synthesized compounds were confirmed by spectroscopic data. The in silico docking studies were performed against human 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase enzyme (PDB It,: 1HWK), and it was observed that compounds 4a and 6a exhibited maximum binding affinity with target protein having binding energies -8.3 and -7.9 kcal, respectively. Results: Compound 4a interacts with amino acids Va1805 with distance 1.89 angstrom and Met656, Thr558, and Glu559 with bonding distances 2.96, 2.70, and 2.20 angstrom, respectively. The in vivo antihyperlipidemic activity results revealed that compound 4a indicated minimum weight increment, ie, 20% compared with 35% weight increment with standard drug atorvastatin during 6 weeks of treatment. Moreover, increment in high-density lipoprotein cholesterol and decrease in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were more prominent in case of 4a compared to atorvastatin with P<0.05. The synthesized compounds were nontoxic and well tolerated because none of the mice were found to suffer from any kind of morbidity and death during 6 weeks of dosing. Conclusion: Based on our pharmacological evaluation, we may propose that compound 4a may act as a lead structure for the design and development of more potent antihyperlipidemic drugs.