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Callicarpins, Two Classes of Rearranged ent-Clerodane Diterpenoids from Callicarpa Plants Blocking NLRP3 Inflammasome-Induced Pyroptosis

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journal contribution
posted on 06.07.2020, 20:30 by De-Bing Pu, Xing-Jie Zhang, De-Wen Bi, Jun-Bo Gao, Yan Yang, Xiao-Li Li, Jing Lin, Xiao-Nian Li, Rui-Han Zhang, Wei-Lie Xiao
Callicarpins A–D (14), possessing an unprecedented A-homoent-clerodane scaffold with a bicyclo[5.4.0]­undecane ring system, and callicarpins E–G (57), with 5/6-fused ent-clerodane diterpenoid skeletons, were isolated from Callicarpaarborea and C. integerrim. Their structures were elucidated by comprehensive spectroscopic data, X-ray crystal diffraction, chemical derivatization, and electronic circular dichroism (ECD) data. Putative biosynthetic pathways for these callicarpins are proposed. Compounds 2, 3b, and 68 showed potent inhibitory effects against the NLRP3 inflammasome with IC50 values from 1.4 to 5.3 μM, and 2 significantly blocked NLRP3 inflammasome-induced pyroptosis by inhibiting Casp-1 activation and IL-1β secretion in J774A.1 cells.