Wu Zhongnan, Zhang Yubo, Wang Guocai, Tang Qing, Li Yaolan, Xie Xiaoqing, Liang Yushen, Cheng Wen
The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University; College of Pharmacy, Guangdong Medical University, Dongguan 523808, China.
Institute of Traditional Chinese Medicine & Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Chin J Nat Med. 2025 Aug;23(8):972-979. doi: 10.1016/S1875-5364(25)60932-0.
Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (1-12) and eight known compounds (13-20) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3-N-1' linkage and C-3-C-4' connection, respectively. Compounds 3-5 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1' linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 9-11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1-3 and 6-11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1-20) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC 5.01 ± 0.14 μmol·L) surpassed that of the positive control (ribavirin, IC 6.23 ± 0.95 μmol·L), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
骆驼蓬是一种重要的经济和药用植物。中国卫生部药品标准记载，骆驼蓬种子已被广泛应用于中药、维吾尔药和蒙药。从骆驼蓬种子中分离出12种新型色胺衍生生物碱（1-12）和8种已知化合物（13-20）。化合物1和2是首次报道的色胺衍生杂聚物实例，分别包含色胺和苯胺片段，具有前所未有的C-3-N-1'键和C-3-C-4'连接。化合物3-5被鉴定为吲哚-喹唑啉杂聚物，在吲哚和喹唑啉衍生片段之间表现出新型的C-3和NH-1'键。化合物6展示了C-C连接的色胺-喹唑啉二聚体的二聚模式。化合物8代表一种具有独特碳骨架的色胺衍生杂二聚体，具有不寻常的螺三环（7）和传统的双环色胺。化合物9-11构成新型的6/5/5/5螺四环色胺衍生生物碱，并呈现出色胺-螺-吡咯里嗪独特的环系。化合物1-3和6-11被鉴定为外消旋体。化合物2、7、9、10和12通过X射线晶体学分析得到证实。所有分离出的化合物（1-20）对呼吸道合胞病毒（RSV）均表现出不同程度的抗病毒功效。值得注意的是，通过蚀斑减少和免疫荧光测定验证，化合物12（IC5.01±0.14μmol·L）的抗RSV活性超过阳性对照（利巴韦林，IC6.23±0.95μmol·L）。从骆驼蓬种子中鉴定出抗RSV化合物可能会促进该植物在抗病毒治疗产品中的开发和应用。
