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Design, Synthesis, Molecular Modelling, and Biological Evaluation of Oleanolic Acid-Arylidene Derivatives as Potential Anti-Inflammatory Agents

Authors Hassan Mir R, Godavari G, Siddiqui NA, Ahmad B, Mothana RA, Ullah R, Almarfadi OM, Jachak SM, Masoodi MH

Received 12 November 2020

Accepted for publication 30 December 2020

Published 4 February 2021 Volume 2021:15 Pages 385—397


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Anastasios Lymperopoulos

Reyaz Hassan Mir,1 Goutami Godavari,2 Nasir Ali Siddiqui,3 Bilal Ahmad,4 Ramzi A Mothana,3 Riaz Ullah,3 Omer M Almarfadi,3 Sanjay M Jachak,2 Mubashir Hussain Masoodi1

1Pharmaceutical Chemistry Division, Department of Pharmaceutical Sciences, University of Kashmir, Srinagar, India; 2Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sahibzada Ajit Singh Nagar, India; 3Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia; 4Department of Molecular Science and Technology, Ajou University, Suwon, South Korea

Correspondence: Mubashir Hussain Masoodi
Pharmaceutical Chemistry Division, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar, Kashmir, 190006, India
Tel +919419076525

Introduction: Oleanolic acid, a pentacyclic triterpenic acid, is widely distributed in medicinal plants and is the most commonly studied triterpene for various biological activities, including anti-allergic, anti-cancer, and anti-inflammatory.
Methods: The present study was carried out to synthesize arylidene derivatives of oleanolic acid at the C-2 position by Claisen Schmidt condensation to develop more effective anti-inflammatory agents. The derivatives were screened for anti-inflammatory activity by scrutinizing NO production inhibition in RAW 264.7 cells induced by LPS and their cytotoxicity. The potential candidates were further screened for inhibition of LPS-induced interleukin (IL-6) and tumour necrosis factor-alpha (TNF-α) production in RAW 264.7 cells.
Results: The results of in vitro studies revealed that derivatives 3d, 3e, 3L, and 3o are comparable to that of the oleanolic acid on the inhibition of TNF-α and IL-6 release. However, derivative 3L was identified as the most potent inhibitor of IL-6 (77.2%) and TNF-α (75.4%) when compared to parent compound, and compounds 3a (77.18%), 3d (71.5%), and 3e (68.8%) showed potent inhibition of NO than oleanolic acid (65.22%) at 10μM. Besides, from docking score and Cyscore analysis analogs (3e, 3L, 3n) showed greater affinity towards TNF-α and IL-1β than dexamethasone.
Conclusion: Herein, we report a series of 15 new arylidene derivatives of oleanolic acid by Claisen Schmidt condensation reaction. All the compounds synthesized were screened for their anti-inflammatory activity against NO, TNF-α and IL-6. From the data, it was evident that most of the compounds exhibited better anti-inflammatory activity.

Keywords: LPS, natural products, IL-1β, IL-6, inflammation, RAW 264.7 cells

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