Synthesis and biological evaluation of pyrazole-fused oleanolic acid derivatives as novel inhibitors of inflammatory and osteoclast differentiation. (15th February 2023)

• Record Type: Journal Article
• Authors: Yu, Yuanyuan; Yuan, Wenlong; Yuan, Jiaqi; Wei, Wenhui; He, Qian; Zhang, Xiaofei; He, Shijun; Yang, Chunhao
• Is Part Of: Bioorganic & medicinal chemistry. Volume 80(2023)
• Publication Date: 2023-02-15
• Subjects: Osteoarthritis -- Oleanolic acid derivatives -- Anti-inflammatory -- IL-1β inhibition -- Antiosteoclastic activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2023.117177
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A series of pyrazole-fused oleanolic acid derivatives were designed and synthesized. The modification of these analogues focused on the substituents screening on the pyrazole ring. The cytotoxicity of these compounds and their anti-inflammatory activities via inhibiting interleukin-1β (IL-1β) production were evaluated in RAW264.7 cells. Most of the derivatives showed significantly improved potency compared with oleanolic acid. Among them, compound 7n exhibited the most potent anti-inflammatory activity on decreasing IL-1β production with low cytotoxicity. Moreover, the further study found 7n could inhibit RANKL-induced osteoclast differentiation on bone marrow-derived macrophages (BMMs). These findings may provide a potential direction for the drug development of osteoarthritis.