Synthesis and cytotoxic activity of ethyl ferulate derivatives as potent anti-inflammatory agents

Abstract

While a range of pharmacological agents are currently used to alleviate inflammation, the clinical administration of many of these anti-inflammatory drugs is associated with high rates of adverse side effects that make them poorly suited to long-term use. Therefore, there is a critical need for the development of novel anti-inflammatory agents. Natural compounds and derivatives like ethyl ferulate have risen to prominence as a foundation for many drug discovery efforts owing to their structural diversity and wide-ranging biological activities. In the present study, 24 ethyl ferulate derivatives were synthesized. Their anti-inflammatory activity was evaluated in vitro using RAW264.7 cells and CCK-8, ELISA, and Western blotting assays. These analyses revealed that most of the synthesized compounds exhibited moderate to high anti-inflammatory activities. In particular, c10 and c23 exerted more pronounced activity than ethyl ferulate or dexamethasone with respect to the suppression of tumour necrosis factor-α production by RAW264.7 cells through the targeting of the NF-κB and MAPK signalling pathways, suggesting that these compounds warrant further investigation.

Graphical Abstract

Keywords:

• Ethyl ferulate
• structural modification
• anti-inflammatory
• RAW 264.7 cells
• natural products

Disclosure statement

No potential conflict of interest was reported by the authors.

Acknowledgments

This work was supported by the National Natural Science Foundation of China [No. 81860798]; Natural Science Foundation of Inner Mongolia [No. 2019BS08016].