Abstract
Hyperlipidemia is a worth-mentioning risk factor in quickly expanding cardiovascular diseases, including myocardial infarction and, furthermore, in stroke.
The present work describes the synthesis of phenolic derivatives
-
and
-
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 ID: 1HWK), and it was observed that compounds
and
exhibited maximum binding affinity with target protein having binding energies -8.3 and -7.9 kcal, respectively.
Compound
interacts with amino acids Val805 with distance 1.89 Å and Met656, Thr558, and Glu559 with bonding distances 2.96, 2.70, and 2.20 Å, respectively. The in vivo antihyperlipidemic activity results revealed that compound
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
compared to atorvastatin with
<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.
Based on our pharmacological evaluation, we may propose that compound
may act as a lead structure for the design and development of more potent antihyperlipidemic drugs.