Abstract

Abstract

The major labdanes in the oleogum resin of Araucaria heterophylla (Salisb.) Franco, 13-epi-cupressic acid (1) and acetyl-13-epi-cupressic acid (2) were used to prepare seven new (3–9), along with one known (10) derivatives. RAW264.7 cells were used to evaluate the anti-inflammatory activity of the derivatives (1–10) via measuring the level of COX-2 expression and IL-6. Pre-treated RAW264.7 cells with 1–10 (except for derivative 7) at 25 µM for 24h exhibited downregulation of COX-2 expression in response to LPS stimulation. Moreover, pre-treatment with compounds 1, 2, or 3 significantly attenuated the LPS-stimulated IL-6 level in RAW264.7 cells (p < 0.05). A docking study was conducted against phospholipase A2 (PLA2), a crucial enzyme in initiating the inflammatory cascade. The significant structural features of compounds (1–10) as PLA2 inhibitors included the carbonyl group at C-4 (free or substituted) and the hydrophobic diterpenoid skeleton. This study suggested 13-epi-cupressic acid as a scaffold for new anti-inflammatory agents.

Details

Title
Design, biological evaluation, and molecular modelling insights of cupressic acid derivatives as promising anti-inflammatory agents
Author
Soliman, Amal F 1 ; Elimam, Diaaeldin M 2 ; El-Senduny, Fardous F 3 ; Alossaimi, Manal A 4 ; Alamri, Mubarak 4 ; Abdel Bar, Fatma M 5 

1  Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University , Mansoura , Egypt 
2  Department of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh University , Kafrelsheikh , Egypt 
3  Chemistry Department, Biochemistry Division, Faculty of Science, Mansoura University , Mansoura , Egypt, Department of Pathology & Laboratory Medicine, Sylvester Comprehensive Cancer Center, Miller School of Medicine , Miami , FL , USA 
4  Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University , Al Kharj , Saudi Arabia 
5  Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University , Al Kharj , Saudi Arabia, Faculty of Pharmacy, Mansoura University , Mansoura , Egypt 
Publication year
2023
Publication date
Dec 2023
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/14756366.2023.2187327
ProQuest document ID
2917547918
Copyright
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.