Hai-Feng Tang

Cytotoxic Asterosaponins Capable of Promoting Polymerization of Tubulin from the Starfish Culcita novaeguineae

Four new asterosaponins, novaeguinosides A (1), B (2), C (3), and D (4), were isolated from the bioactive fraction of the starfish Culcita novaeguineae, as active compounds capable of promoting polymerization of tubulin. Their structures were elucidated by extensive spectroscopic studies and chemical evidence. Compounds 1 and 3 are characterized by sulfated side chains not previously found in asterosaponins, and 1 is the first example of a trisulfated asterosaponin. In the side chains of 2 and 4, the 26-carboxylic acid function is found as an amide derivative of taurine, which is a rare feature and first encountered among asterosaponins. All the asterosaponins showed cytotoxicity against two human tumor cell lines.

Polyhydroxysteroidal Glycosides from the Starfish Anthenea chinensis

Ten new polyhydroxysteroidal glycosides, anthenosides B-K (2-11), were isolated from the ethanol extract of the starfish Anthenea chinensis. Their structures were elucidated by extensive spectroscopic studies and chemical evidence. The unprecedented carbohydrate chain 6-O-methyl-beta-d-galactofuranosyl-(1-->3)-(6-O-methyl-beta-d-galactofuranose) was present in all the compounds except compounds 10 and 11. Compounds 5, 7, a mixture of 8 and 9, and a mixture of 10 and 11 showed inhibitory activity against human tumor K-562 and BEL-7402 cells. Furthermore, the mixture of 10 and 11 also exhibited cytotoxicity against human tumor U87MG cells and promoted tubulin polymerization.

Hillasides A and B, two new cytotoxic triterpene glycosides from the sea cucumber Holothuria hilla Lesson

Two new triterpene glycosides, hillasides A (1) and B (2), were isolated from the sea cucumber H. hilla Lesson, together with one known glycoside holothuria B (3). Their structures were deduced by extensive spectral analysis and chemical evidences. The presence of conjugated double bonds [22E,24-diene] in the aglycone of 1 is a rare structural feature among sea cucumber glycosides. The two glycosides showed significant cytotoxicity against eight human tumour cell lines (A-549, MCF-7, IA9, CAKI-1, PC-3, KB, KB-VIN and HCT-8) with IC 50 in the range of 0.1–3.8 μg/ml.

Ceramides and cerebrosides from the marine bryozoan Bugula neritina inhabiting South China Sea

From the marine bryozoan Bugula neritina inhabiting South China Sea, a new ceramide named (2S,3R,4E)-2-(14′-methyl-pentadecanoylamino)-4-octadecene-l,3-diol (1) and a new cerebroside named 1-O-(β-d-glucopyranosyl)-(2S,3R,4E)-2-(heptadecanoylamino)-4-octadecene-l,3-diol (6), together with one known ceramide (2) and three known cerebrosides (3, 4, and 5), were isolated. Their structures were deduced by extensive spectral analysis and chemical evidences. Compound 1 is branched with a methyl [–CH(CH3)2] in the fatty acid moiety, which is a rare structural feature among ceramides. Compound 6 is a new cerebroside with 17 carbons in the fatty acid moiety, while 5 is a new natural product which was isolated from a natural origin for the first time.

Two New Triterpenoid Saponins Cytotoxic to Human Glioblastoma U251MG Cells from Ardisia pusilla

Two new triterpenoid saponins, ardipusillosides IV and V (1 and 2, resp.), together with one known saponin, ardisiacrispin B (3), were isolated from the whole plants of Ardisia pusilla A. DC. Their structures were deduced by extensive spectral analysis and chemical evidences. Compound 1 contains a glycosylated glycerol residue which is a very rare structural feature among triterpenoid glycosides and has been so far found only in the genus Ardisia. All the saponins exhibited significant cytotoxicity against human glioblastoma U251MG cells, but did not affect the growth of primary cultured human astrocytes.

Bryostatin 5 induces apoptosis in acute monocytic leukemia cells by activating PUMA and caspases

Acute leukemia is a malignant clonal hematopoietic stem cell disease. In the current study, we examined the effects of bryostatin 5 on acute monocytic leukemia cells in vitro and in vivo. We also explored the mechanisms and pathways underlying the increase in apoptosis induced by bryostatin 5. Bryostatin 5 inhibited the growth of primary acute monocytic leukemia cells and U937 cells in a dose- and time-dependent manners. Bryostatin 5 also induced an increase in apoptosis and a decrease in the mitochondrial membrane potential (MMP) in U937 cells. Transmission electron microscopy (TEM) revealed that bryostatin 5-treated cells displayed typical apoptotic characteristics (chromatin condensation, karyopyknosis and formation of crescents and apoptotic bodies). In addition, bryostatin 5 increased the expression of P53 upregulated modulator of apoptosis (PUMA) and slightly increased P53 expression. Bryostatin 5 also significantly decreased Bcl-XL expression and significantly increased the expression levels of Bak, Bax, cleaved caspase 9 and cleaved caspase 3. The pro-apoptotic activity of bryostatin 5 in U937 cells was inhibited by PUMA siRNA and z-LEHD-fmk (a specific caspase 9 inhibitor). In addition, the PUMA siRNA significantly affected the expression of cleaved caspase 9, whereas z-LEHD-fmk had little effect on the expression of PUMA. The results suggest that PUMA is located upstream of caspase 9 in this apoptotic signaling pathway. These novel findings provide mechanistic insight into the induction of apoptosis by bryostatin 5 and might facilitate the development of clinical strategies to enhance the therapeutic efficacy of treatments for acute monocytic leukemia.

1-Methyl-1,2,3,4-tetra-hydro-carbolin-2-ium-3-carboxyl-ate.

The title compound, C13H14N2O2, is a natural product isolated from Cicer arietinum L. (chickpea). The benzene ring and pyrrole rings display planar conformations and the piperidine ring has a half-chair conformation. Intermolecular C—H⋯π interactions between a methyl H atom and the pyrrole ring of an adjacent molecule are present in the crystal structure.