Design, biological evaluation, and molecular modelling insights of cupressic acid derivatives as promising anti-inflammatory agents.

The major labdanes in the oleogum resin of (Salisb.) Franco, 13-epi-cupressic acid () and acetyl-13-epi-cupressic acid () were used to prepare seven new (-), along with one known () derivatives. RAW264.7 cells were used to evaluate the anti-inflammatory activity of the derivatives (-) measuring the level of expression and IL-6. Pre-treated RAW264.7 cells with - (except for derivative ) at 25 µM for 24h exhibited downregulation of expression in response to LPS stimulation. Moreover, pre-treatment with compounds , , or significantly attenuated the LPS-stimulated IL-6 level in RAW264.7 cells ( < 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 (-) 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.