Diverse structures and antihepatoma effect of sesquiterpenoid dimers from Artemisia eriopoda by AKT/STAT signaling pathway

Artemannuols A–C, novel sesquiterpenoid–flavonol hybrids with antihepatoma activity from Artemisia annua

“…The coupling constant between H-2 and H 2 -3 ( J = 9.6 Hz) indicated the Z-configuration of the Δ 2,3 -double bond. Further comparison of the NMR data of 1 with those of the previously reported (1R,4S,7R,10R)-or (1S,4R,7S,10S)-2-bisabolen-4,10,11-triol showed that their 13 C NMR data around the key chiral carbons were almost identical [δ C 41.3 vs. 41.3 and 41.0 (C-1); 69.4 vs. 69.9 and 69.9 (C-4); 37.6 vs. 37.1 and 39.5 (C-7); 79.0 vs. 79.0 and 79.5 (C-10); 16.3 vs. 16.6 and 16.8 (C-14)], supporting their same stereochemistry. 19,20 In order to determine the absolute configuration of 1, the ECD calculations of two possible isomers, 1a (1R,4S,7R,10R) and 1b (1S,4R,7S,10S), were conducted using the time-dependent density functional theory (TD-DFT) method at the B3LYP/6-31+G(d,p) level, in which the calculated ECD curve of 1a matched well with the experimental ECD spectrum (Fig.…”

“…General experimental procedures and instruments were consistent with our previous reports, 13,14 and are provided in the ESI †…”

“…19,20 Generally, if the chemical shifts of the olefinic carbons (C-2 and C-3) show a difference of more than Δδ 3.0 ppm, the relative configuration of C-1 and C-4 is trans (1S,4R) or (1R,4S), while a difference of less than Δδ 2.0 ppm indicates a cis (1S,4S) or (1R,4R) configuration. The relative configuration of C-7 is related to that of C-1 and is determined by comparing the 1 H and 13 C NMR data of CH 3 -14. When the chemical shifts of C-14 and H-14 are less than δ C 16.0 and δ H 0.85, the relative stereochemistry of C-1 and C-7 is (1S,7R) or (1R,7S), and conversely, it is (1S,7S) or (1R,7R).…”

“…12 Our previous investigation on the genus Artemisia afforded a series of terpenoids with antihepatoma activity, involving the sesquiterpenoid dimers of cadinane, guaianolide, cadinanemonocyclofarnesane, cadinane-bisabolene, cadinane-eudesmane, cadinane-humulane, and rotundane-guaiane, the sesquiterpenoid trimers of guaiane-rotundane-guaiane, and the sesquiterpenoid monomers of guaiane, gemmarane, and eudesmane. [13][14][15][16][17][18] In our continuous search for new antihepatoma constituents from natural sources, three novel sesquiterpenoid-flavonol hybrids, artemannuols A-C (1-3), were isolated and identified from A. annua (Fig. 1).…”

Artemeriopolides A–D, two types of sesquiterpenoid dimers with rare carbon skeletons from Artemisia eriopoda and their antihepatoma cytotoxicity

“…[9][10][11][12][13][14] Our previous investigation suggested that the EtOH extract of A. eriopoda showed cytotoxicity against HepG2, Huh7 and SK-Hep-1 cells, from which novel sesquiterpenoid dimers with antihepatoma activity were isolated. 15 Pharmacological studies demonstrated that artemeriopodin G7 could inhibit cell migration and invasion, induce G2/M cell cycle arrest and cell apoptosis in HepG2 cells, and exert an antihepatoma effect by targeting PDGFRA protein through the AKT/STAT signaling pathway. During a continuing pursuit of complex and bioactive SDs from Artemisia species, [9][10][11][12][13] artemeriopolides A-D (1-4), four novel sesquiterpenoid dimers belonging to two carbon skeleton types, were isolated and characterized from A. eriopoda, which has been considered as an alternative traditional Chinese herb to A. annua in southern China and used to treat rheumatoid arthritis, edema, and thanatophidia in folk medicine.…”