New Bisbenzylisoquinolines, Fatty Acid Amidic Aporphines, and a Protoberberine from Formosan <i>Cocculus orbiculatus</i>

Two new bisbenzylisoquinoline alkaloids, (+)-coccuorbiculatine A (2) and (+)-10-hydroxyisotrilobine (3), two new amidic aporphines, a mixture of (+)-laurelliptinhexadecan-1-one (6) and (+)-laurelliptinoctadecan-1-one (7), and one new protoberberine (−)-4-methoxy-13,14-dihydrooxypalmatine (8) have been isolated from the stems of Taiwanese Cocculus orbiculatus. The structures were established on the basis of extensive analysis of spectroscopic data and by comparison with known related metabolites. Cytotoxicity of the isolated compounds was examined toward HepG2, Hep3B, MCF-7, and MDA-MB-231 cancer cell lines. Alkaloids 1 and (−)-sinococuline (9) showed significant inhibitory activity against the target cell lines

Anti-Lymphangiogenic Alkaloids from the Zoanthid <i>Zoanthus vietnamensis</i> Collected in Taiwan

Eleven new secondary metabolites [kuroshines H–J (1–3), 27-methyl glycinate zoanthenamine (4), 27-hydroxyzoanthenamine (5), 27-methyl glycinate kuroshine A (6), 27-hydroxykuroshine A (7), 3β-hydroxy-28-deoxyzoanthenamine (8), 14α-hydroxy-28-deoxyzoanthenamine (9), 27-hydroxy-28-deoxyzoanthenamine (10), and kuroshine K (11)], along with seven known compounds (12–18), were isolated from the zoantharian Zoanthus vietnamensis. The structures of all isolated components were elucidated by spectroscopic data (IR, MS, NMR, and UV), especially 2D NMR analyses. The relative configurations of 1 and 2 were confirmed by using single-crystal X-ray crystallography. Compounds 1–3 were found to have an unprecedented ether linkage between C-15 and C-28, while the unusual substituent methyl glycinate, attached at C-27 in compounds 4 and 6, was found for the first time in zoanthamine-type alkaloids. The anti-lymphangiogenic activities of 17 isolated compounds were evaluated. Compounds 4, 5, and 10 exerted promising anti-lymphangiogenic functions by reducing cell growth and tube formation of human lymphatic endothelial cells (LECs). In addition, the structure–activity relationships of the isolated alkaloids against lymphangiogenesis of LECs are discussed

New Flavans, Spirostanol Sapogenins, and a Pregnane Genin from <i>Tupistra chinensis</i> and Their Cytotoxicity

Seven new compounds, including three new flavans [tupichinol A−C (1−3)], three new spirostanol sapogenins [tupichigenin D−F (4−6)], and one new pregnane genin [tupipregnenolone (7)], together with 18 known compounds, were isolated from the underground parts of Tupistra chinensis. The structures of the new compounds were elucidated by spectroscopic analysis and chemical evidence. The structures and relative stereochemistry of 1 and 9 were further confirmed by single-crystal X-ray crystallographic analysis. Compounds Δ25(27)-pentrogenin, 10, and ranmogenin A showed 100%, 96%, and 80% inhibition, respectively, against human gastric tumor (NUGC) cells at a concentration of 50 μM. Δ25(27)-pentrogenin showed 100% inhibition against human nasopharyngeal carcinoma (HONE-1) cells at a concentration of 50 μM

Anti-Lymphangiogenic Alkaloids from the Zoanthid <i>Zoanthus vietnamensis</i> Collected in Taiwan

Eleven new secondary metabolites [kuroshines H–J (1–3), 27-methyl glycinate zoanthenamine (4), 27-hydroxyzoanthenamine (5), 27-methyl glycinate kuroshine A (6), 27-hydroxykuroshine A (7), 3β-hydroxy-28-deoxyzoanthenamine (8), 14α-hydroxy-28-deoxyzoanthenamine (9), 27-hydroxy-28-deoxyzoanthenamine (10), and kuroshine K (11)], along with seven known compounds (12–18), were isolated from the zoantharian Zoanthus vietnamensis. The structures of all isolated components were elucidated by spectroscopic data (IR, MS, NMR, and UV), especially 2D NMR analyses. The relative configurations of 1 and 2 were confirmed by using single-crystal X-ray crystallography. Compounds 1–3 were found to have an unprecedented ether linkage between C-15 and C-28, while the unusual substituent methyl glycinate, attached at C-27 in compounds 4 and 6, was found for the first time in zoanthamine-type alkaloids. The anti-lymphangiogenic activities of 17 isolated compounds were evaluated. Compounds 4, 5, and 10 exerted promising anti-lymphangiogenic functions by reducing cell growth and tube formation of human lymphatic endothelial cells (LECs). In addition, the structure–activity relationships of the isolated alkaloids against lymphangiogenesis of LECs are discussed

Anti-Lymphangiogenic Alkaloids from the Zoanthid <i>Zoanthus vietnamensis</i> Collected in Taiwan

Eleven new secondary metabolites [kuroshines H–J (1–3), 27-methyl glycinate zoanthenamine (4), 27-hydroxyzoanthenamine (5), 27-methyl glycinate kuroshine A (6), 27-hydroxykuroshine A (7), 3β-hydroxy-28-deoxyzoanthenamine (8), 14α-hydroxy-28-deoxyzoanthenamine (9), 27-hydroxy-28-deoxyzoanthenamine (10), and kuroshine K (11)], along with seven known compounds (12–18), were isolated from the zoantharian Zoanthus vietnamensis. The structures of all isolated components were elucidated by spectroscopic data (IR, MS, NMR, and UV), especially 2D NMR analyses. The relative configurations of 1 and 2 were confirmed by using single-crystal X-ray crystallography. Compounds 1–3 were found to have an unprecedented ether linkage between C-15 and C-28, while the unusual substituent methyl glycinate, attached at C-27 in compounds 4 and 6, was found for the first time in zoanthamine-type alkaloids. The anti-lymphangiogenic activities of 17 isolated compounds were evaluated. Compounds 4, 5, and 10 exerted promising anti-lymphangiogenic functions by reducing cell growth and tube formation of human lymphatic endothelial cells (LECs). In addition, the structure–activity relationships of the isolated alkaloids against lymphangiogenesis of LECs are discussed

Anti-Lymphangiogenic Alkaloids from the Zoanthid <i>Zoanthus vietnamensis</i> Collected in Taiwan

Eleven new secondary metabolites [kuroshines H–J (1–3), 27-methyl glycinate zoanthenamine (4), 27-hydroxyzoanthenamine (5), 27-methyl glycinate kuroshine A (6), 27-hydroxykuroshine A (7), 3β-hydroxy-28-deoxyzoanthenamine (8), 14α-hydroxy-28-deoxyzoanthenamine (9), 27-hydroxy-28-deoxyzoanthenamine (10), and kuroshine K (11)], along with seven known compounds (12–18), were isolated from the zoantharian Zoanthus vietnamensis. The structures of all isolated components were elucidated by spectroscopic data (IR, MS, NMR, and UV), especially 2D NMR analyses. The relative configurations of 1 and 2 were confirmed by using single-crystal X-ray crystallography. Compounds 1–3 were found to have an unprecedented ether linkage between C-15 and C-28, while the unusual substituent methyl glycinate, attached at C-27 in compounds 4 and 6, was found for the first time in zoanthamine-type alkaloids. The anti-lymphangiogenic activities of 17 isolated compounds were evaluated. Compounds 4, 5, and 10 exerted promising anti-lymphangiogenic functions by reducing cell growth and tube formation of human lymphatic endothelial cells (LECs). In addition, the structure–activity relationships of the isolated alkaloids against lymphangiogenesis of LECs are discussed

(−)-Liriopein B Suppresses Breast Cancer Progression via Inhibition of Multiple Kinases

Numerous breast cancer patients who achieve an initial response to HER-targeted therapy rapidly develop resistance within one year, leading to treatment failure. Observations from clinical samples indicate that such resistance correlates with an increase in Src, EGFR, and PI3K/Akt activities and a decrease in PTEN activity. Furthermore, Akt survival signaling activation is also found in tumors treated by toxic chemotherapeutic agents. Because cotreatment with a PI3K inhibitor is a promising strategy to delay acquired resistance by preventing secondary gene activation, we therefore investigated the effects of a newly identified compound, (−)-Liriopein B (LB), on PI3K/Akt signaling activity in breast cancer cells. Our results showed that nontoxic doses of LB are able to inhibit AKT activation in both luminal-like MCF-7 and basal-like MDA-MB-231 breast cancer cells. Low doses of LB also inhibited cell migration, invasion, and cancer-stem cell sphere formation. Suppression of EGF-induced EGFR and ERK1/2 activation by LB might contribute in part to retardation of cancer progression. Furthermore, LB increases sensitivity of MDA-MB-231 cells to gefitinib in vitro, suggesting that EGFR may not be the only target of LB. Finally, a small scale in vitro kinase assay screen demonstrated that LB has a potent inhibitory effect on multiple kinases, including PI3K, Src, EGFR, Tie2, lck, lyn, RTK5, FGFR1, Abl, and Flt. In conclusion, this study demonstrates for the first time that the compound LB improves tumor therapeutic efficacy and suggests LB as a promising candidate for studying new leads in the development of kinase inhibitors

Cytotoxicity data of natural phenanthrenes isolated from <i>C. arisanensis</i>.

a<p>Doxorubicin (Doxo) was used as the positive control.</p

New Cytotoxic Monotetrahydrofuran Annonaceous Acetogenins from <i>Annona </i><i>m</i><i>uricata</i>

Three new monotetrahydrofuran annonaceous acetogenins, muricin H (1), muricin I (2), and cis-annomontacin (3), along with five known acetogenins, annonacin, annonacinone, annomontacin, murisolin, and xylomaticin, were isolated from the seeds of Annona muricata. Additionally, two new monotetrahydrofuran annonaceous acetogenins, cis-corossolone (4) and annocatalin (5), together with four known ones, annonacin, annonacinone, solamin, and corossolone, were isolated from the leaves of this species. The structures of all new isolates were elucidated and characterized by spectral and chemical methods. These new acetogenins exhibited significant activity in in vitro cytotoxic assays against two human hepatoma cell lines, Hep G2 and 2,2,15. Compound 5 showed a high selectivity toward the Hep 2,2,15 cell line

Effects of ursolic acid (UA) treatment on plasma (A) aspartate aminotransferase (AST) and (B) alanine aminotransferase (ALT) concentration in rats at 24 hr after sham operation (Sham) or trauma-hemorrhagic shock (T–H).

<p>Rats were administered with either vehicle (Veh) or UA. Data are shown as mean±SEM (n = 6). ^*<i>p</i><0.05 compared to Sham; ^#<i>p</i><0.05 compared to T–H+Veh.</p