Teiko Yamada

Comparison of the effects of curcumin and curcumin glucuronide in human hepatocellular carcinoma HepG2 cells.

Curcumin is a yellow pigment found in turmeric (Curcuma Longa L.), and is reported, in recent studies, to have several pharmacological effects, including anti-oxidant, anti-inflammatory, anti-tumour and lipid-lowering properties. However, as most curcumin is conjugated when absorbed through the intestine, free curcumin is present at extremely low levels inside the body. Therefore, curcumin metabolites have been presumed to be responsible for the curcumin bioactivity. In this study, we first confirmed that curcumin glucuronide is the major metabolite of curcumin found in the plasma after oral administration of curcumin in rats. Next, we synthesised curcumin glucuronide and compared the effects of curcumin and curcumin glucuronide on gene expression in a human hepatoma cell line (HepG2). We found that the effects of curcumin glucuronide are weaker than those of curcumin and that this difference is related to relative absorption rates of curcumin and curcumin glucuronide into HepG2 cells.

Synthesis and biological evaluation of novel 9-functional heterocyclic coupled 7-deoxy-9-Dihydropaclitaxel analogue

Novel 9-functional heterocyclic coupled 7-deoxy-9-dihydropaclitaxel analogues 17 and 22-24 synthesized from a natural taxoid 5-cinnamoyltriacetyltaxicin-I (3) and their biological evaluation in tubulin assembly activity and cytotoxicity in vitro against several human tumor cell lines are first presented. The biologically tested results show that 17, 22 and 23 are inactive in tubulin assembly assay and have no more remarkable cytotoxicities against human tumor cell lines SK-OV3, WIDR and MCF-7, though 22 and 23 exhibit more potent cytotoxicity against human liver cancer and human esophagus cancer cell lines (BEL-7402 and ECa-109) than paclitaxel.

Two novel pseudoalkaloid taxanes from the Chinese yew, Taxus chinensis var. mairei

Abstract Two pseudoalkaloid taxane diterpenoids were isolated from seeds of the Chinese yew tree Taxus chinensis var. mairei. Their structures were established as 2α,9α,10β,13α-tetraacetoxy-5α(3′-methylamino-3′-phenyl)-propionyloxy-taxa-4(20),11-diene and 7β,9α,10β,13α-tetraacetoxy-5α(3′-methylamino-3′-phenyl)-propionyloxy-taxa-4(20),11-diene, with the aid of NMR spectral and FAB-MS data analysis.

Taxane Diterpenoids From the Seeds of Chinese Yew, Taxus Mairei

Abstract Nine taxane diterpenoids were isolated from the seeds of Taxus mairei. One of them was a novel compound with the structure (1) which was established as 9α, 10β, 13α-triacetoxy-5α(3′ -methylamino-3′ -phenyl)-propionyloxy-taxa-4(20), 11 -diene on the basis of 1H NMR data and HR-EI-MS analysis.

Two new alkaloidal taxoids from the needles of Taxus canadensis

Two new taxanes with a dimethylamino group on the C-5 side chain were identified for the first time in the needles of the Canadian yew, Taxus canadensis. Their structures were characterized as 7β,10β,13α-triacetoxy-5α-(3′-dimethylamino-3′-phenylpropanoyl)oxy-2α-hydroxy-2(3→20)abeotaxa-4(20),11-dien-9-one (1) and 2α,10β-diacetoxy-9α-hydroxy-5α-(3′-dimethylamino-3′-phenylpropanoyl)oxy-3,11-cyclotax-4(20)-en-13-one (2).

Two Novel Bicyclic 3,8-Secotaxoids From the Needles of Tax Us Mairei

Abstract Two novel bicyclic taxane diterpenoids were isolated from the needles of the Chinese yew, Taxus mairei, the structures were established as (3E,8E)-5α-hydroxy-2α,7β,9,10β,20-pentaacetoxy-3,8-secotaxa-3,8,11-trien-13-one and (3E,8E)-2α,5α, 20-trihydroxy-7β,9 10β-triacetoxy-3,8-secotaxa-3,8,11 -trien-13-one with the aid of spectroscopic techniques.

Synthesis and degranulation-inhibiting activities of the proposed apteniols B, C, and G.

The synthesis of compounds with the structures proposed for the oxyneolignan apteniols B, C, and G is described. The diphenyl ether skeletons of the proposed apteniols were formed via Ullmann ether synthesis. In particular, the spectral data for the synthesized apteniols B, C, and G did not agree with those previously reported for the isolated compounds. Furthermore, the synthesized proposed apteniol B did not show degranulation-inhibiting activity, while the prepared proposed apteniols C and G exhibited activities considerably weaker than that of the methyl ester of proposed apteniol A. Graphical Abstract The synthesis of proposed apteniols B, C, and G is described. The spectral data of the synthesized apteniols B, C, and G did not agree with those of isolated compounds.

Syntheses and biological activities of the proposed structure of apteniol A and its derivatives

We describe the syntheses of the proposed structure of diphenyl ether oxyneolignan, apteniol A and its derivatives. The diphenyl ether moiety of proposed apteniol A was formed via Ullmann ether synthesis, but the spectral data of the synthesized apteniol A did not agree with that in previous studies. The dimethyl ester derivative of the proposed apteniol A was found to enhance neurite outgrowth in PC12 cells and inhibit antigen-induced degranulation in RBL-2H3 cells. Graphical Abstract Proposed apteniol A (1) and its derivatives were synthesized and the dimethyl ester (6) was found to enhance neurite outgrowth and inhibit antigen-induced degranulation.

7,8beta-dihydroponasterone A, a new phytoecdysteroid from the needles of the Japanese Yew, Taxus cuspidata

A new plant ecdysteroid 7,8b-dihydroponasterone A, together with ponasterone A, were isolated from the methanol extract of the needles of the Japanese yew, Taxus cuspidata. Their structures were elucidated on the basis of spectroscopic analysis including 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMQC and HMBC and confirmed by high-resolution FABMS data.

Novel Dimeric Taxoids via Highly Regio- and Stereospecific Diels–Alder Cycloadditions of Taxinine B and Taxicine I Derivatives

Abstract Oxidation of 20-hydroxy-4,5-ene-7-oxotaxinine 4 derived from a natural taxoid taxinine B via four steps gave a corresponding aldehyde 5 , which afforded a new dimeric taxoid 6 through regio- and stereospecific hetero Diels–Alder cycloaddition. Similar hetero Diels–Alder reaction of 4:5,6:7-diene aldehyde 13 gave two new dimeric taxoids 14 and 15 . In addition, Lewis acid-catalyzed Diels–Alder reaction of 20-hydroxy-4:5,6:7-diene taxoid 12 with N -methylmaleimide led to cycloadduct exo - 16 and γ-butyrolactone endo - 17 , while a similar Lewis acid-catalyzed Diels–Alder reaction of 12 with taxoid 7a yielded only cycloadduct exo - 18 . 7a and 7b , the two isomers of alcohol 4 , yielded two 5-ethyl substituted derivatives 8 and 9 through highly stereoselective Michael addition in the presence of diethylaluminum chloride. The structure and stereochemistry of the dimers were established by spectroscopic experiments including 2D NMR studies.