Antihyperlipidemic studies of newly synthesized phenolic derivatives: in silico and in vivo approaches
Authors Aqeel MT, ur-Rahman N, Khan A, Ashraf Z, Latif M, Rafique H, Rasheed U
Received 4 December 2017
Accepted for publication 20 April 2018
Published 9 August 2018 Volume 2018:12 Pages 2443—2453
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Sukesh Voruganti
Muhammad Tahir Aqeel,1 Nisar ur-Rahman,1 Arif-ullah Khan,2 Zaman Ashraf,3 Muhammad Latif,4 Hummera Rafique,5 Usman Rasheed1
1Department of Pharmacy, COMSATS Institute of Information Technology Abbottabad, Abbottabad, Pakistan; 2Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; 3Department of Chemistry, Allama Iqbal Open University, Islamabad, Pakistan; 4College of Medicine, Centre for Genetics and Inherited Diseases (CGID), Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia; 5Department of Chemistry, University of Gujrat, Gujrat, Pakistan
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.
Keywords: phenolic derivatives, synthesis, antihyperlipidemic, in silico docking, HMG CoA reductase, atorvastatin
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]