Rare oxoisoaporphine alkaloids from Menispermum dauricum with potential anti-inflammatory activity

• Published in: Phytochemistry (Oxford) 2024-09, Vol.225, p.114170, Article 114170
• Main Authors: Guo, Rui, Wang, Cun-Lin, Cao, Xiao-Juan, Yao, Xiao-Juan, Qiao, Xin, Meng, Ya-Tian, Zhang, Tong, Zhang, Qiong
• Format: Article
• Language: English
• Subjects: Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Anti-inflammatory activity; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Aporphines - chemistry; Aporphines - isolation & purification; Aporphines - pharmacology; Dose-Response Relationship, Drug; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Menispermaceae; Menispermum - chemistry; Menispermum dauricum DC; Mice; Molecular Structure; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Oxoisoaporphine alkaloid; RAW 264.7 Cells; Structure-Activity Relationship
• ISSN: 0031-9422; 1873-3700; 1873-3700
• DOI: 10.1016/j.phytochem.2024.114170

Eleven alkaloids including four previously undescribed oxoisoaporphine alkaloids, menisoxoisoaporphines A-D (1–4), four known analogues (5–8), and three aporphine alkaloids (9–11), were isolated and identified from the rhizomes of Menispermum dauricum. Their structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction analyses. Among them, compounds 1 and 4 were the first samples of oxoisoaporphine with C-6 isopentylamino moiety, and 2 was a rare C-4 methylation product of oxoisoaporphine alkaloid. The in vitro anti-inflammatory activity of compounds 1–11 was performed by evaluating the inhibition of NO level in LPS-induced RAW264.7 macrophages. Among them, compound 4 exhibited the most potent NO inhibition activity with an IC50 value of 1.95 ± 0.33 μM. The key structure-activity relationships of those oxoisoaporphine alkaloids for anti-inflammatory effects have been summarized. Four undescribed oxoisoaporphine alkaloids, together with seven known analogues were isolated from the rhizomes of Menispermum dauricum DC., which were evaluated for their their inhibitory activity towards the LPS-induced NO production in RAW 264.7 cells. Menisoxoisoaporphine D exhibited the most potent NO inhibition activity with an IC50 value of 1.95 ± 0.33 μM. [Display omitted] •Four undescribed alkaloids were isolated from the rhizomes of Menispermum dauricum.•Menisoxoisoaporphine A was the first sample of oxoisoaporphine with C-6 isopentylamino moiety.•Menisoxoisoaporphine B was a rare C-4 methylation product of oxoisoaporphine alkaloid.•Menisoxoisoaporphine D showed the most potent NO inhibition activity (IC50 1.95 ± 0.33 μM).