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

ABSTRACT: 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 ID: 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 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 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.

SUBMITTER: Aqeel MT

PROVIDER: S-EPMC6089105 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Aqeel Muhammad Tahir MT Ur-Rahman Nisar N Khan Arif-Ullah AU Ashraf Zaman Z Latif Muhammad M Rafique Hummera H Rasheed Usman U

Drug design, development and therapy 20180809

<h4>Background</h4>Hyperlipidemia is a worth-mentioning risk factor in quickly expanding cardiovascular diseases, including myocardial infarction and, furthermore, in stroke.<h4>Methods</h4>The present work describes the synthesis of phenolic derivatives <b>4a</b>-<b>e</b> and <b>6a</b>-<b>c</b> 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-hydrox ...[more]

PMID: 30127594

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

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

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