Minpei Kuroda

Cholestane glycosides with potent cytostatic activities on various tumor cells from ornithogalum saundersiae bulbs

Abstract Five cholestane glycosides ( 1 – 5 ) including three new ones ( 3 – 5 ) with potent cytostatic activity on leukemia HL -60 cells were isolated from Ornithogalum saundersiae bulbs. Compound 1 , a main constituent in the bulbs, was revealed to be exceptionally cytostatic against various malignant tumor cells and effective to mouse P388 leukemia in in vivo evaluation.

Natural products reveal cancer cell dependence on oxysterol-binding proteins

Cephalostatin 1, OSW-1, ritterazine B and schweinfurthin A are natural products that potently, and in some cases selectively, inhibit the growth of cultured human cancer cell lines. The cellular targets of these small molecules have yet to be identified. We have discovered that these molecules target oxysterol binding protein (OSBP) and its closest paralog, OSBP-related protein 4L (ORP4L)--proteins not known to be involved in cancer cell survival. OSBP and the ORPs constitute an evolutionarily conserved protein superfamily, members of which have been implicated in signal transduction, lipid transport and lipid metabolism. The functions of OSBP and the ORPs, however, remain largely enigmatic. Based on our findings, we have named the aforementioned natural products ORPphilins. Here we used ORPphilins to reveal new cellular activities of OSBP. The ORPphilins are powerful probes of OSBP and ORP4L that will be useful in uncovering their cellular functions and their roles in human diseases.

Novel cholestane glycosides from the bulbs of Ornithogalum saundersiae and their cytostatic activity on leukemia HL-60 and MOLT-4 cells

Abstract Two novel 24(23→22) abeo -cholestane glycosides with a six-membered hemiacetal ring system and a five-membered acetal ring system ( 2 , 3 ), designated as saundersioside A and B, respectively, together with a new 16,23-epoxy-5β-cholestane glycoside ( 1 ) were isolated from the bulbs of Ornithogalum saundersiae . Their structures were determined by detailed analysis of the 1 H and 13 C NMR spectra, including various two-dimensional spectroscopy, and acid-catalyzed hydrolysis. The conformations of the 16,23-epoxy moiety of 1 and the six-membered hemiacetal moiety of 2 and 3 were studied through molecular mechanics and molecular dynamics calculation methods. Compound 3 bearing a p -methoxybenzoyl group at the saccharide part showed potent cytostatic activity on leukemia HL-60 and MOLT-4 cells, and the effect to HL-60 cells was revealed to be mediated partially through induction of apoptosis by cell morphology and DNA fragmentation.

Steroidal saponins from Nolina recurvata stems and their inhibitory activity on cyclic AMP phosphodiesterase

Seven steroidal saponins were isolated from the stems of Nolina recurvata, five of which appeared to be new compounds and were assigned as spirosta-5,25(27)-diene-1 beta,3 beta-diol (neoruscogenin) 1-O--O-alpha-L-rhamnopyranosyl-(1--> 2)-O-[beta-D-xylopyranosyl-(1-->3)]-alpha-L-arabinopyranoside-, (25S)-spirost-5-ene-1 beta,3 beta-diol [(25S)-ruscogenin] 1-O-{O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-xylopyranosyl-(1--> 3)]-alpha-L-arabinopyranoside}, neoruscogenin 1-O-{O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-xylopyranosyl-(1--> 3)]-beta-D-fucopyranoside}, 26-O-beta-D-glucopyranosyl-22-O-methylfurosta-5,25(27)-diene-1 beta,3 beta,22 xi,26-tetrol 1-O--O-alpha-L-rhamnopyranosyl-(1--> 2)-O-[beta-D-xylopyranosyl-(1-->3)]-alpha-L-arabinopyranoside- and 26-O-beta-D-glucopyranosylfurosta-5,20(22),25(27)-triene-1 beta,3 beta,26-triol 1-O-{O-alpha-L-rhamnopyranosyl-(1--> 2)-alpha-L-arabinopyranoside}. The isolated saponins were evaluated for their inhibitory activity on cyclic AMP phosphodiesterase to identify new compounds with medicinal potential.

Steroidal Saponins from the Rhizomes of Paris polyphylla var. chinensis and their Cytotoxic Activity on HL-60 Cells

Abstract A new spirostanol steroidal saponin, along with ten known saponins, which were based upon (25R)-spirost-5-en-3β-o1 (diosgenin) or (25R)-spirost-5-ene-3β5,17α-diol (pennogenin) as the aglycones, were isolated from the rhizomes of Paris polyphylla var. chinensis. Spectral data, including two-dimensional NMR, and the result of hydrolytic cleavage showed that the structure of the new saponin was pennogenin 3-0-{O−α-L-rhamnopyranosyl-(1→4)-O a-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside}. The isolated saponins were evaluated for their cytotoxic activity on human promyelocytic leukemia HL-60 cells.

Steroidal saponins from the underground parts of Ruscus aculeatus and their cytostatic activity on HL-60 cells

Phytochemical examination of the underground parts of Ruscus aculeatus has been undertaken as part of systematic study of plants of the Liliaceae. Six new spirostanol saponins and five new furostanol saponins were isolated, and their structures were assigned on the basis of spectroscopic analysis, including two-dimensional NMR techniques, and hydrolysis. Ruscogenin diglycoside with three acetyl groups attached to the inner galactosyl moiety and its corresponding 26-glucosyloxyfurostanol saponin showed cytostatic activity on leukemia HL-60 cells.

Steroidal saponins from the bulbs of Lilium candidum.

Five new spirostanol saponins and a new furostanol saponin were isolated from the fresh bulbs of Lilium candidum. Their structures were elucidated on the basis of spectroscopic analysis, including two-dimensional NMR spectroscopic techniques and the result of acid hydrolysis. The isolated saponins contained a branched triglycoside moiety assigned as O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->6)]-beta - D-glucopyranose with the formation of an O-glycosidic linkage to C-3 of the aglycone as the common structural feature. The inhibitory activity of the saponins on Na+/K+ ATPase was evaluated.

Steroidal saponins from the aerial parts of Dracaena draco and their cytostatic activity on HL-60 cells

Chemical examination of the aerial parts of Dracaena draco has led to the isolation of a total of nine steroidal saponins, including five new ones. The structures of the new saponins were determined by spectral data and a few chemical transformations to be (23S,24S)-spirosta-5,25(27)-diene-1 beta,3 beta,23,24-tetrol 1-O-{O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl)-(1-->2)-alpha-L -arabinopyranosyl} 24-O-beta-D-fucopyranoside, (23S,24S)-spirosta-5,25(27)-diene-1 beta,3 beta, 23,24-tetrol 1-O-{O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L -arabinopyranoside}, (23S,24S)-spirosta-5,25(27)-diene-1 beta,3 beta,23,24-tetrol 1-O-{O-(4-O- acetyl-alpha-L-rhamnopyranosyl)-(1-->2)-alpha-L-arabinopyransoide} , (23S)-spirosta-5,25(27)-diene-1 beta,3 beta,23-triol 1-O-{O-alpha-L- rhamnopyranosyl)-(1-->2)-alpha-L-arabinopyranoside} and (23S,24S)-spirosta-5,25(27)-diene-1 beta,3 beta,23-triol 1-O-{O-(4-O-acetyl-alpha-L-rhamnopyranosyl)-(1-->2)-alpha-L- arabinopyranoside}. The isolated saponins were evaluated for their cytostatic activity on leukemia HL-60 cells.

Hypoglycemic effects of clove (Syzygium aromaticum flower buds) on genetically diabetic KK-Ay mice and identification of the active ingredients

Clove (Syzygium aromaticum flower buds) EtOH extract significantly suppressed an increase in blood glucose level in type 2 diabetic KK-Ay mice. In-vitro evaluation showed the extract had human peroxisome proliferator-activated receptor (PPAR)-γ ligand-binding activity in a GAL4-PPAR-γ chimera assay. Bioassay-guided fractionation of the EtOH extract resulted in the isolation of eight compounds, of which dehydrodieugenol (2) and dehydrodieugenol B (3) had potent PPAR-γ ligand-binding activities, whereas oleanolic acid (4), a major constituent in the EtOH extract, had moderate activity. Furthermore, 2 and 3 were shown to stimulate 3T3-L1 preadipocyte differentiation through PPAR-γ activation. These results indicate that clove has potential as a functional food ingredient for the prevention of type 2 diabetes and that 2–4 mainly contribute to its hypoglycemic effects via PPAR-γ activation.

Steroidal saponins from Hosta longipes and their inhibitory activity on tumour promoter-induced phospholipid metabolism of HeLa Cells

Three new spirostanol saponins and two new furostanol saponins were isolated from the underground parts of Hosta longipes. Their structures were determined to be (25R)-5 alpha-spirostane-2 alpha, 3 beta-diol (gitogenin) 3-O-{O-alpha-L -rhamnopyranosyl-(1-->2)-beta-D-galactopyranoside}, gitogenin 3-O-{O-alpha-L-rhamnopyranosyl-(1-->2) -O-[beta-D-glucopyranosyl-(1-->4)]-beta-D-galactopyranoside-, (25R)-5 alpha-spirostan-3 beta-ol (tigogenin) 3-O-{O-alpha-L-rhamnopyranosyl-(1-->2) -O-[beta-D-glucopyranosyl-(1-->4)]-beta-D-galactopyranoside-, 26-O-beta-D-glucopyranosyl-22-O-methyl-(25R)-5 alpha-furostane-2 alpha,3 beta, 22 xi,26-tetrol 3-O-{O-alpha-L-rhamnopyranosyl -(1-->2)-beta-D-galactopyranoside} and 26-O-beta -D-glucopyranosyl-22-O-methyl-(25R)-5 alpha-furostane-2 alpha,3 beta,22 xi,26-tetrol 3-O-{O-alpha-L -rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl -(1-->4)]-beta-D-galactopyranoside}, respectively. The isolated saponins and their derivatives were examined for inhibitory activity on 12-O-tetradecanoylphorbor-13-acetate-stimulated 32P-incorporation into phospholipids of HeLa cells as the primary screening test to find new antitumour-promoter compounds.