Synthesis And Anti-inflammatory Activity Evaluation Of Pterostilbene 1H-1,2,3-triazole Derivatives

Inflammation is a common clinical disease,and the dysregulation of inflammatory response can promote the development of various diseases,including cancer etc.Therefore,the research and development of anti-inflammatory drugs has always been the focus of attention.At present,the most commonly used anti-inflammatory drugs are non-steroidal anti-inflammatory drugs,whose adverse reactions will bring inevitable troubles to patients.Therefore,researchers are committed to developing some effective anti-inflammatory drugs without side effects.As a natural product with anti-inflammatory,anti-oxidation,anti-tumor and other physiological activities,pterostilbene has been widely used as lead structures in the design of small molecule drugs.1H-1,2,3 triazole also is a useful pharmacophore,which is of great significance to improve the biological activity of related structures.In this study,a total of 72compounds of two series were designed and synthesized with the structure of pterostilbene-1H-1,2,3 triazole.The structures of all the derivatives were confirmed by¹HNMR,¹³CNMRand HRMS,and D24 were confirmed by X-ray single crystal diffraction.The anti-inflammatory activities of title compounds were evaluated by using Griess assay to detect their inhibitory activities against NO released in an established LPS-induced RAW264.7 cell model.The cytotoxicity of title compounds was detected by MTT assay,and the anti-inflammatory mechanism of the target compounds was investigated by Western blot.The results showed that all tested compounds did not exhibited toxicities to cells at the concentration of 20μM.All pterostilbene-1H-1,2,3triazole derivatives could inhibit the NO release in different degrees,and E6(IC₅₀=0.6μM)had the strongest inhibitory effect.We found that compound E6 could inhibit the expression of COX-2 and i NOS in a concentration-dependent.Further studies showed that E6 could exert anti-inflammatory activity by blocking MAPK and JAK/STAT signaling pathway.The results provided the thinking and direction for the development of pterostilbene derivatives as anti-inflammatory drugs.