Tamotsu Nikaido

Acylated cholestane glycosides from the bulbs of Ornithogalum saundersiae

Abstract Phytochemical examination of the bulbs of Ornithogalum saundersiae led to the isolation of three new acylated cholestane glycosides. Their structures were elucidated, on the basis of the spectroscopic data and chemical evidences, and by comparing them with those of known compounds, as 3βP,16βP,17α-trihydroxycholest-5-en-22-one 16- O -β- d -xylopyranosyl-(1→3)-(2- O -acetyl-α- l -arabinopyranoside), 3β,16β,17α-trihydroxycholest-5-en-22-one 16- O -(2- O -4-methoxybenzoyl-βP- d -xylopyranosyl)-(1→3)-(2- O -acetyl-α- l -arabinopyranoside) and 3β,16β,17α-trihydroxy-cholest-5-en-22-one 16- O -(2- O -3,4-dimethoxybenzoyl-β- d -xylopyranosyl)-(1→3)-(2- O -acetyl-α- l -arabinopyranoside). Inhibitory activity on cyclic AMP phosphodiesterase of the cholestane glycosides was evaluated.

Rosmarinic acid production by Coleus forskohliihairy root cultures

Coleus forskohlii hairy root cultures were found to produce forskolin and rosmarinic acid (RA) as the main metabolites. The growth and RA production by C. forskohlii hairy root cultures in various liquid media were examined. The hairy root cultures showed good growth in hormone-free Murashige and Skoog medium containing 3% (w/v) sucrose (MS medium), and Gamborg B5 medium containing 2% (w/v) sucrose (B5 medium). RA yield reached 4.0 mg (MS medium) and 4.4 mg (B5 medium) after 5 weeks of culture in a 100 ml flask containing 20 ml of each medium. Hairy root growth and RA were also investigated after treatment with various concentrations of yeast extract (YE), salicylic acid (SA) and methyl jasmonic acid (MJA). RA production in a 100 ml flask containing 20 ml B5 medium reached 5.4 mg (1.9 times more than control) with treatment of 0.01 or 1% (w/v) YE, 5.5 mg (2.0 times more than control) with treatment of 0.1 mM SA, and the maximum RA content with 9.5 mg per flask (3.4 times more than control) was obtained in the hairy roots treated with 0.1 mM MJA. These results suggest that MJA is an effective elicitor for production of RA in C. forskohlii hairy root cultures.

Steroidal saponins from Smilax riparia and S. China

Two new neotigogenin glycosides were isolated from the rhizomes and roots of Smilax riparia and a new isonarthogenin glycoside from those of S. china. The structures were elucidated by a combination of spectroscopic analysis and hydrolysis followed by spectral and chromatographic analysis. Several known saponins were also isolated and identified. The inhibitory activity of the saponins on cAMP phosphodiesterase was examined.

Biologically active triterpenoid saponins from Acanthopanax senticosus.

Three new triterpenoid saponins, acanthopanaxosides A (1), B (7), and C (13), were isolated from the leaves of Acanthopanax senticosus, together with 12 known saponins. The structures of these new saponins were established as 3-O-beta-D-glucopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-30-nor-olean-12,20(29)-dien-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-6-O-acetyl-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (1), 3-O-beta-D-glucopyranosyl-(1-->2)-alpha-L-arabinopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-6-O-acetyl-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (7), and 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-3beta-hydroxyolean-12-ene-28,29-dioic acid (13), on the basis of spectroscopic analysis and chemical degradation. Among the known compounds, sessiloside and tauroside H1 are reported for the first time from A. senticosus. The biological activity of compounds 1-15 was examined against pancreatic lipase. Ciwujianoside C1 (6), tauroside H1 (11), 3-O-alpha-rhamnopyranosyl-(1-->2)-alpha-arabinopyranosyl mesembryanthemoidigenic acid (12), acanthopanaxoside C (13), sessiloside (14), and chiisanoside (15) inhibited pancreatic lipase activity in vitro. In turn, ciwujianosides C2 (3), D2 (5), C4 (8), and C3 (10) and hederasaponin B (9) enhanced this enzyme.

Assay of nematocidal activity of isoquinoline alkaloids using third-stage larvae of Strongyloides ratti and S. venezuelensis.

We examined the effects of isoquinoline alkaloids in vitro in an effort to identify a treatment for Strongyloides stercoralis larva migrans in humans. Infective third-stage larvae of S. ratti and S. venezuelensis were used as model nematodes for S. stercoralis. Nematocidal activity was evaluated by the 50% paralysis concentration (PC(50)). Most of the tested isoquinoline alkaloids had activity for S. ratti and S. venezuelensis. We then evaluated in vitro cytotoxicity, which was the 50% inhibition concentration (IC(50)) of the compounds using HL60 tissue-culture cells. Three of the compounds (protopine, D-corydaline, and L-stylopine) which exhibited strong nematocidal activity, showed little cytotoxicity. In addition, we examined the relationship between nematocidal activity and cytotoxicity using the PC(50)/IC(50) ratio. A ratio equivalent to or lower than that calculated for the currently prescribed strongyloidosis treatments, ivermectin, albendazole and thiabendazole, was observed for allocryptopine, protopine, dehydrocorydaline, D-corydaline, L-stylopine, and papaverine. In contrast, the PC(50)/IC(50) ratios for protopine, D-corydaline, and L-stylopine were substantially more favorable. Therefore, protopine, D-corydaline, and L-stylopine were identified as potential effective treatments for strongyloidosis.

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 bulbs of Triteleia lactea and their inhibitory activity on cyclic AMP phosphodiesterase.

The chemical compounds in the bulbs of Triteleia lactea have been analysed as a part of our systematic study of plants of the subfamily Allioideae in Liliaceae. Thirteen steroidal saponins, seven of which appeared to be new compounds, were isolated. The structures of the new saponins were elucidated on the basis of the spectroscopic analysis, including two-dimensional NMR techniques, and hydrolysis. Inhibitory activity of the isolated saponins on cyclic AMP phosphodiesterase was evaluated to identify new compounds with medicinal potential.

Picrodendrin and related terpenoid antagonists reveal structural differences between ionotropic GABA receptors of mammals and insects.

Twenty-eight picrotoxane terpenoids, including picrodendrins isolated from the Euphorbiaceae plant, Picrodendron baccatum (L.) Krug and Urban, have been evaluated for their ability to inhibit the specific binding of [3H]EBOB, the noncompetitive antagonist of ionotropic GABA receptors, to rat-brain and housefly (Musca domestica L.)-head membranes. Picrodendrin Q was the most potent competitive inhibitor of [3H]EBOB binding, with IC50 values of 16 nM (rat) and 22 nM (Musca). We find that the spiro gamma-butyrolactone moiety at the 13-position, which contains a carbonyl group conjugated with an unsaturated bond, and the substituents at the 4-position play important roles in the interaction of picrodendrins with their binding site in rat receptors. In contrast, such structural features are not strictly required in the case of the interaction with Musca receptors; the spiro saturated gamma-butyrolactone moiety at the 13-position, which bears the 16-sp3 carbon atom, and the hydroxyl groups at various positions are somewhat tolerated. Quantitative structure-activity studies have clearly shown that the electronegativity of the 16-carbon atom and the presence or absence of the 4- and 8-hydroxyl groups are important determinants of the potency of nor-diterpenes in Musca receptors, while the negative charge on the 17-carbonyl oxygen atom is likely important in the case of rat receptors. These findings indicate that there are significant differences between the structures of the complementary binding sites in rat GABA receptors and Musca GABA receptors. We also infer differences between native Musca GABA receptors and the Drosophila Rdl subunit-containing homo-oligomeric GABA receptors in the structures of their binding sites.

Polyoxypregnane glycosides from the flowers of Dregea volubilis.

Three novel polyoxypregnane glycosides, volubiloside A, B and C (1-3), were isolated from the flowers of Dregea volubilis Linn., and their structures were elucidated as drevogenin D-3-O-beta-D-glucopyranosyl (1-->4)-6-deoxy-3-O-methyl-beta-D-allopyranosyl (1-->4)-beta-D-cymaropyranosyl (1-->4)-beta-D-cymaropyranoside, drevogenin D-3-O-beta-D-glucopyranosyl (1-->4)-6-deoxy-3-O-methyl-beta-D-allopyranosyl (1-->4)-beta-D-cymaropyranosyl (1-->4)-beta-D-digitoxopyranoside and drevogenin P-3-O-beta-D-glucopyranosyl (1-->4)-6-deoxy-3-O-methyl-beta-D-allopyranosyl (1-->4)-beta-D-cymaropyranosyl (1-->4)-beta-D-cymaropyranoside, respectively, on the basis of extensive NMR experiments, MALDI-TOF MS, and some chemical strategies.

Gaultherins A and B, two lignans from Gaultheria yunnanensis

Abstract Two lignans, trivially named gaultherins A ( 1 ) and B ( 2 ), were isolated from the roots of Gaultheria yunnanensis (Ericaceae). Their structures were deduced as 5-methoxy-(+)-isolariciresinol-9,9′-diacetate ( 1 ) and (+)-lyoniresinol-9,9′-diacetate ( 2 ), based upon physicochemical properties, spectral analyses and chemical degradation.