Calycindaphines A-J, Daphniphyllum alkaloids from the roots of Daphniphyllum calycinum

Abstract

Ten new Daphniphyllum alkaloids, calycindaphines A-J (1-10), together with seventeen known alkaloids were isolated from the roots of Daphniphyllum calycinum. Their structures were established by extensive spectroscopic methods and compared with data from literature. Compound 1 is a novel alkaloid with a new rearrangement C₂₂ skeleton with the 5/8/7/5/5 ring system. Compound 2 represents the second example of calyciphylline G-type alkaloids. Compound 10 is the first example of secodaphniphylline-type alkaloid absent of the oxygen-bridge between C-25/C-29. The possible biogenetic pathways of 1 and 2 were also proposed. All the isolated compounds were evaluated for their bioactivities in three cell models. Compounds 22, 23, and 26 showed significant NF-κB transcriptional inhibitory activity at a concentration of 50 μM. Compounds 16 and 18 exhibited significant TGF-β inhibitory activity in HepG2 cells. Compounds 24 and 26 induced autophagic puncta and mediated the autophagic marker LC3-II conversion in HEK293 cells.

Fig. 1. Chemical structures of compounds 1–27.

Fig. 2. Key ¹H–¹H COSY and HMBC correlations of compounds 1–10.

Fig. 3. Key NOESY correlations of compounds 1–4, 6, and 8.

Fig. 4. Experimental and calculated ECD spectra of compound 1.

Scheme 1. Biogenetic pathway proposed for compounds 1 and 2, daphhimalenine A, and calyciphylline G.

Fig. 5. The effects of isolated alkaloids on TNFα-induced NF-κB activation (a), TGF-β/SMAD pathway (b), and cell autophagy (c and d).