Design, synthesis, in vitro and in vivo biological evaluation of pterostilbene derivatives for anti-inflammation therapy

Abstract

Pterostilbene (PST) is a naturally derived stilbene compound in grapes, blueberries, and other fruits. It is also a natural dietary compound with a wide range of biological activities such as antioxidant, anti-inflammatory, antitumor, and so on. Structural modifications based on the chemical scaffold of the pterostilbene skeleton are of great importance for drug discovery. In this study, pterostilbene skeletons were used to design novel anti-inflammatory compounds with high activity and low toxicity. A total of 30 new were found and synthesised, and their anti-inflammatory activity and safety were screened. Among them, compound E2 was the most active (against NO: IC₅₀ = 0.7 μM) than celecoxib. Further studies showed that compound E2 exerted anti-inflammatory activity by blocking LPS-induced NF-κB/MAPK signalling pathway activation. In vivo experiments revealed that compound E2 had a good alleviating effect on acute colitis in mice. In conclusion, compound E2 may be a promising anti-inflammatory lead compound.

GRAPHICAL ABSTRACT

Keywords:

• Anti-inflammation therapy
• NF-κB/MAPK signalling pathway
• pterostilbene
• drug discovery
• inflammatory bowel diseases

Disclosure statement

The authors confirm that this article’s content has no conflict of interest.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (22207028), the Natural Science Foundation of Anhui Province (2108085MH318 and 2208085QH275), the Scientific Research Foundation for Advanced Talents of Hefei University (22RC29), and the "Biology and Medicine" key subject of Hefei University (2023xk05).