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 (39), along with one known (10) derivatives. RAW264.7 cells were used to evaluate the anti-inflammatory activity of the derivatives (110) via measuring the level of COX-2 expression and IL-6. Pre-treated RAW264.7 cells with 110 (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 (110) 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   VIAFID ORCID Logo  ; Elimam, Diaaeldin M 2   VIAFID ORCID Logo  ; El-Senduny, Fardous F 3   VIAFID ORCID Logo  ; Alossaimi, Manal A 4   VIAFID ORCID Logo  ; Alamri, Mubarak 4 ; Abdel Bar, Fatma M 5   VIAFID ORCID Logo 

 Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt 
 Department of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt 
 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 
 Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia 
 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
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.