Original articles
Yong Li, Yuxun Zhu, Zhaoxin Zhang, Li Li, Yunbao Liu, Jing Qu, Shuanggang Ma, Shishan Yua. Antinociceptive grayanane-derived diterpenoids from flowers of Rhododendron molle[J]. Acta Pharmaceutica Sinica B, 2020, 10(6): 1073-1082

Antinociceptive grayanane-derived diterpenoids from flowers of Rhododendron molle
Yong Li, Yuxun Zhu, Zhaoxin Zhang, Li Li, Yunbao Liu, Jing Qu, Shuanggang Ma, Shishan Yua
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Abstract:
Twelve new grayanoids (1-12) along with five known compounds were isolated from flowers of Rhododendron molle. Their structures were fully characterized using a combination of spectroscopic analyses, computational calculations, and single crystal X-ray diffraction. Rhomollone A (1) possesses an unprecedented 5/6/6/5 tetra-cyclic ring system (B-nor grayanane) incorporating a cyclopentene-1,3-dione scaffold. Rhodomollein XLIII (2) is a dimeric grayanoid, containing a novel 14-membered heterocyclic ring with a C2 symmetry axis. The antinociceptive activities of compounds 3, 4, 6, 7, and 12-17 were evaluated by an acetic acid-induced writhing test. Among them, compounds 3, 7, 12, 15 and 16 displayed significant antinociceptive activities at a dose of 20 mg/kg with inhibition rates ranging from 41.9% to 91.6%. Compounds 6 and 13 inhibited 46.0% and 39.4% of the acetic acid-induced writhes at a dose of 2 mg/kg, while compound 17 inhibited 34.3% of the writhes at a dose of 0.4 mg/kg.
Key words:    Rhododendron molle    Diterpenoid    Grayanane    Dimeric    Antinociceptive    Analgesic   
Received: 2019-07-25     Revised: 2019-08-23
DOI: 10.1016/j.apsb.2019.10.013
Funds: This work was supported by grants from the National Natural Science Foundation of China (Nos. 21572274 and 21732008) and the CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-1-010, China).
Corresponding author: Shishan Yu     Email:yushishan@imm.ac.cn
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Yong Li
Yuxun Zhu
Zhaoxin Zhang
Li Li
Yunbao Liu
Jing Qu
Shuanggang Ma
Shishan Yua

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