The phenyl - and -L-idopyranosiduronic acids and some other aryl glycopyranosiduronic acids

Condensation of 1,2,3,4,6-penta-O-acetyl-á-l-idopyranose (1) with phenol yielded phenyl 2,3,4,6-tetra-O-acetyl-α- (2) and α-l-idopyranoside (4). Deacetylation of 2 and 4 afforded phenyl α and β-l-idopyranosides (3 and 5), respectively, the structures of which were verified by periodate oxidation studies. A platinum-catalyzed oxidation of 3 and 5 produced the amorphous phenyl α- and β-L-idopyranosiduronic acids (9 and 11), respectively, which were isolated as the crystalline cyclohexylammonium salts. Phenyl β- and α-d-glucopyranosiduronic acids are apparent minor byproducts of the catalytic oxidations, resulting from an inversion at C-5. _p-Nitrophenyl α-d-mannopyranosiduronic acid and _p-nitrophenyl α- and β-d-galactopyranosiduronic acids are also described.     

Phomoeuphorbins A-D, azaphilones from the fungus Phomopsis euphorbiae

Four azaphilones, named phomoeuphorbins A-D (1-4) were isolated from cultures of Phomopsis euphorbiae, an endophytic fungus isolated from Trewia nudiflora. Structures of 1-4 were established on the basis of spectroscopic analyses, including application of 2D NMR spectroscopic techniques. Phomoeuphorbins A and C exhibited very weak inhibitory activities against HIV replication in C8166 cells in vitro.     

Biological evaluation of 3'-O-alkylated analogs of salacinol, the role of hydrophobic alkyl group at 3' position in the side chain on the α-glucosidase inhibitory activity

Four analogs with 3′-O-alkyl groups (9a: CH₃, 9b: C₂H₅, 9c: C₁₃H₂₇ or 9d: CH₂Ph) instead of the 3′-O-sulfate anion in salacinol (1), a naturally occurring potent α-glucosidase inhibitor, were synthesized by the coupling reaction of 1,4-dideoxy-1,4-epithio-d-arabinitols (18a and 18b) with appropriate epoxides (10a-10d). These analogs showed equal or considerably higher inhibitory activity against rat small intestinal α-glucosidases than the original sulfate (1), and one of them (9d) was found more potent than currently used α-glucosidase inhibitors as antidiabetics. Thus, introduction of a hydrophobic moiety at the C3′ position of this new class of inhibitor was found beneficial for onset of stronger inhibition against these enzymes.     

Compounds from Kadsura angustifolia with anti-HIV activity

Four new cycloartane triterpenoids, angustific acid A (1), angustific acid B (2), angustifodilactone A (3) and angustifodilactone B (4) were isolated from the branches of Kadsura angustifolia together with six known compounds, micranoic acid B (5), nigranoic acid (6), schisandrin (7), schisantherin D (8), interiotherin B (9), schisantherin B (10). Their structures were established on the basis of extensive spectroscopic data analyses and comparison with spectroscopic data reported. Compound 1, characterized by the presence of a C-16/C-17, C-20/C-21 conjugated diene and a C-1/C-7 ester bridge formed in rings A and B, provided a novel structural skeleton for 3,4-secocycloartane triterpenoid derivatives. In addition, the anti-HIV activities of these compounds were determined in infected C8166 cells, and it was found that angustific acid A (1) exhibited the most potent anti-HIV activity with an EC₅₀ value of 6.1 μg/mL and a therapeutic index of more than 32.8.     

Unusual stilbenoids and a stilbenolignan from seeds of Syagrus romanzoffiana

Stilbenoids, syagrusins A-B (1-2), and a stilbenolignan, 5-hydroxyaiphanol (3), along with three known phenylpropanoids (4-6), were isolated from seeds of Syagrus romanzoffiana. Compounds 1 and 2 possess unusual 1,4,4a,9a-tetrahydrofluoren-9-one and bicyclo[3.3.0]octanedione skeletons, respectively, whereas compound 3 is a stilbenolignan belonging to a very rare structural class of plant secondary metabolites. Their structures were elucidated by spectroscopic analyses. Compounds 1-3 exhibited moderate inhibitory activity against α-glucosidase with IC₅₀ values of 16.9 μM (1), 23.7 μM (2) and 12.8 μM (3), respectively.     

Rare merosesquiterpenoids from basidiomycete Craterellus odoratus and their inhibition of 11β-hydroxysteroid dehydrogenases

Rare merosesquiterpenoids, craterellins A-C (1-3), were isolated from cultures of basidiomycete Craterellus odoratus together with the previously known massarinolin C (4). Structures of 1-3 were elucidated on the basis of extensive spectroscopic analysis. Compounds 1-3 possess a rare, epoxymethylenecyclohexanetriol-bicyclofarnesane sesquiterpene hybrid skeleton. Compounds 1-4 were evaluated for their inhibitory activities against two isozymes of 11β-hydroxysteroid dehydrogenases (11β-HSD1 and 11β-HSD2).     

Synthesis, characterization and anti-tumor activity of moxifloxacin-copper complexes against breast cancer cell lines

Novel moxifloxacin-copper complexes were synthesized, characterized and screened for anti-proliferative and apoptosis-inducing activity against multiple human breast cancer cell lines (hormone-dependent MCF-7 and T47D as well as hormone-independent MDA-MB-231 and BT-20). The results indicated that the parent compound moxifloxacin (1) does not exert any inhibitory activity against breast cancer cell lines examined. On the other hand, the copper conjugate 2 and its nitrogen adducts 3-5 exerted growth inhibitory and apoptosis-inducing activity against breast cancer cell lines without any substantial effect on non-tumorigenic breast epithelial cells MCF-10A at equimolar concentration, suggesting a cancer cell-specific activity. BT-20 cells were more sensitive to compounds 2 and 3, while compounds 4 and 5 exerted significant anti-proliferative and apoptosis-inducing effects on T47D, MDA-MB-231 and BT-20 cell lines. Our results suggest that these novel compounds could be useful for the treatment of breast cancer in the future.     

Three new cytotoxic aryltetralin lignans from Sinopodophyllum emodi

Three new aryltetralin lignans, 4-acetyl-4-demethyl-podophyllotoxin (1) and sinolignans A, B (2-3), and two new natural products (4-5), were isolated from the roots and rhizomes of Sinopodophyllum emodi together with twelve known lignans (6-17). Their structures and stereochemistry were elucidated on the basis of spectroscopic evidence, and circular dichroism (CD) method. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines. Compared with etoposide, compounds 1, 6-9, and 13 showed more potent cytotoxicities against two tumor cell lines. On the basis of IC₅₀ values, deoxypodophyllotoxin (7) was about 579 and 1123 times more toxic than etoposide in HeLa and KB cell lines, respectively. The preliminary SAR study indicated that an oxygenated group at C-7′ might decrease cytotoxicity against two cell lines, which was different from most previous studies. However, this needs to be systematically verified by extensive pharmacological experiments.     

Synthesis and biological activity of novel thiazolidin-4-ones with a carbohydrate moiety

Some novel 2-aryl-3-[5-deoxy-1,2-O-isopropylidene-α-d-xylofuranose-5-C-yl] thiazolidin-4-ones were synthesized by the three-component condensation of an amino sugar 1, an aromatic aldehyde 2, and mercaptoacetic acid 3 in the presence of DCC and DMAP at room temperature. Two diastereoisomers 4 and 5 were afforded as the main products in totally isolated yields of 25.4-70%. The reaction was carried out with almost no observed stereoselectivity except in the case of 2c, which showed a moderate stereoselectivity. The structures of the new compounds were determined by NMR spectroscopy and mass spectrometry (MS), and the configuration of the newly generated chiral carbon (C-2) in the thiazolidin-4-one ring was tentatively assigned based on the X-ray crystallographic structure of 5d and the comparison of their corresponding NMR signals. The antitumor (human cervical cancer cells) activity and the inhibition against the glycosidases (α-glucosidase, β-glucosidase, α-amylase) have been evaluated for the new compounds, some of which exhibited antitumor activity.     

Bis-sesquiterpenes and diterpenes from Chloranthus henryi

Bis-sesquiterpenes, henriols A (1), B (2), C (3), and D (4), and three diterpenes, henrilabdanes A (5), B (6), and C (7), together with two known bis-sesquiterpenes and three known labdane diterpenes, were isolated from the ethanol extract of the roots of Chloranthushenryi. Their structures and absolute configurations were elucidated by NMR spectroscopic, X-ray crystallographic and CD analyses. Compounds 1, 5, 6 and 7 showed moderate hepatoprotective activities with IC₅₀ values of 0.19, 0.66, 0.09 and 0.18 μM, respectively. They were not studied further due to the weak effects noted. Compounds 3 and 8 exhibited cytotoxic activities against three types of cancer cell lines including the hepatoma (BEL-7402), human gastric carcinoma (BGC-823), and colon cancer (HCT-8).     

Synthesis of rotenoid derivatives with cytotoxic and topoisomerase II inhibitory activities

6-Deoxyclitoriacetal (1) and a series of 11 further derivatives of it (2-12) were synthesized and evaluated for their cytotoxic and topoisomerase IIα inhibitory activities. Compounds bearing epoxide (2), morpholine (6) and benzylamine (10) moieties showed promising in vitro cytotoxic activities against four cancer cell lines, with IC₅₀ values ranging from 0.38 to 0.73 μM. These three compounds also strongly inhibited topoisomerase II activity at 68.3-93.5% and showed a moderately high DNA intercalating property.     

Bioactive polyhydroxylated sterols from the marine sponge Haliclona crassiloba

Four new polyhydroxylated sterols, named halicrasterols A–D (1–4), together with six known analogs (5–10) were isolated from the marine sponge Haliclona crassiloba. Compounds 1 and 2 represented rare examples of steroids featuring 17(20)E-double bonds. The structures of 1–10 were elucidated by spectroscopic analysis and comparison with reported data. This is the first report of a steroid profile for this species. The antimicrobial activities of 1–10 were evaluated against a panel of bacterial and fungal strains in vitro, and compounds 4 and 9 showed moderate activity against some of the Gram-positive strains with MICs ranging from 4 to 32 μg/mL.     

Reaktionen der glucuronsäure : 7. Mitt. Oxidationen an d-glucofuranosidurono-6,3-lactonen

Methyl α-D- (1) and methyl β-D-glucofuranosidurono-6,3-lactone (5) were oxidized at C-2 or C-5, 1,2-O-isopropylidene-α-D- (10) and 1,2-O-cyclohexylidene-α-D-glucofuranurono-6,3-lactone (11) at C-5 by various methods to the corresponding D-arabino- or D-xylo-hexulofuranosiduronolactones. In contrast to the starting materials 5, 10, and 11, the 5-uloses 15, 17, and 18 do not exhibit reducing power in alkaline Cu²⁺ solutions. Methyl 5-O-benzyl-α-D- and methyl 5-O-benzyl-β-D-arabino-2-hexulofuranosidurono-6,3-lactone reduce Benedict solution at room temperature.     

Antiproliferative and apoptotic sesquiterpene lactones from Carpesium faberi

Four new (1-4) and 13 known (5-17) sesquiterpene lactones along with two known diterpenes (18, 19) were isolated from the whole plant of Carpesium faberi. The new structures were elucidated by means of spectroscopic techniques and some chemical transformations to be pseudoguaian-1α(H)-8α,12-olide-4β-O-β-d-glucopyranoside (1), 4β,10α-dihydroxy-5α(H)-1,11(13)-guaidien-8α,12-olide (2), 4β,10β-dihydroxy-5α(H)-1, 11(13)-guaidien-8β,12-olide (3), and (4S)-acetyloxyl-11(13)-carabren-8β,12-olide (4). All isolates were tested against MCF-7 human breast cancer cells using the MTT assay. Among them, the sesquiterpene lactones (except tomentosin 17) possessing an α-methylene-γ-lactone moiety were found to have in vitro antiproliferative activities, with IC₅₀ values of 3.0-38.8 μg/mL. The effects of four selected sesquiterpene lactones (guaianolide 2, carabranolide 4, pseudoguaianolide 9, eudesmanolide 13) on the cell cycle were examined using flow cytometry (FCM).     

Efficient synthesis and biological evaluation of epiceanothic acid and related compounds

Epiceanothic acid (1) is a naturally occurring, but very rare pentacyclic triterpene with a unique pentacyclic triterpene (PT) structure. An efficient synthesis of 1 starting from betulin (3) has been accomplished in 12-steps with a total yield of 10% in our study. Compound 1 and selected synthetic intermediates were further evaluated as anti-HIV-1 agents, inhibitors of glycogen phosphorylase (GP), and cytotoxic agents. Compound 1 exhibited moderate HIV-1 inhibition. Most importantly, compound 5, with an opened A-ring, showed significant GP inhibitory activity with an IC₅₀ of 0.21 μM, suggesting a potential for development as an anti-diabetic agent. On the other hand, compound 12, with a closed A-ring, showed potent cytotoxicity against A549 and MCF-7 human tumor cell lines, with IC₅₀ values of 0.89 and 0.33 μM, respectively. These results suggest that the A-ring of PTs is an important pharmacophore that could be modified to involve different biological activities.     

Design, synthesis and biological evaluation of new arylpiperazine derivatives bearing a flavone moiety as α1-adrenoceptor antagonists

Elaborate study on the three-dimensional model of α₁-adrenoceptor (α₁-AR) antagonists led to the development of a series of new arylpiperazine derivatives bearing a flavone nucleus as α₁-AR antagonists. The in vitro activities were evaluated and compounds 1, 4, 10, 13 and 15 showed activities close to the reference compound (Prazosin).     

New monoterpene glycosides and phenolic compounds from Distylium racemosum and their inhibitory activity against ribonuclease H

Two new monoterpene glycosides, distyloside A-B (1-2), and a new megastigmane glucoside, iso-dihydrodendranthemoside A (3) were isolated from twigs and leaves of Distylium racemosum, along with five known phenolic compounds (4-8). The structures were established via spectroscopic techniques and chemical transformations, and the absolute stereochemistry of 3 was determined by Mosher’s esterification. A homogeneous fluorescence resonance energy transfer (FRET) quenching assay was used to determine the inhibitory activity of isolates (1-8) on the ribonuclease H enzymes from HIV-1, 2, human, and Escherichia coli. Among them, 6″-O-galloylsalidroside (6) showed potent inhibitory effects with an IC₅₀ value of 3.5 μM on HIV-2, and 1.7 μM on human RNase H, respectively.     

Thermal solvent-free synthesis of novel pyrazolyl chalcones and pyrazolines as potential antimicrobial agents

A novel approach was adopted for the synthesis of series of new pyrazolyl chalcones (3a-c) by the reaction of 5-chloro-3-methyl-1-phenylpyrazole-4-carboxaldehyde (1) with different 5-acetylbarbituric acid derivatives (2a-c) under thermal solvent-free condition. The chalcones were then converted to the corresponding pyrazolines (4a-c) under the same condition in excellent yields. All the synthesized compounds were characterized using elemental analysis and spectral data (IR, ¹H NMR, and mass spectrometry). The synthesized compounds were tested for their antimicrobial activity by disk diffusion assay with slight modifications against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. The investigation of antimicrobial screening revealed that compounds (3a-4c) showed good antibacterial and antifungal activities, respectively. Among the screened compounds, 3b showed more potent inhibitory activity (MIC = 12.5 μg/ml) nearly to that of standard antibiotics ciprofloxacin, griseofulvin and fluconazole.     

Synthesis of cinnamoyl ketoamides as hybrid structures of antioxidants and calpain inhibitors

The excessive calpain activation causes serious cellular damage or even cell death in neurological disorders such as stroke and Alzheimer’s disease. Oxidative stress has also been implicated in the initiation or progression of neurodegenerative diseases. In the present studies, a series of cinnamoyl ketoamides 4a-4j were synthesized as hybrid structures of antioxidants and calpain inhibitors. Cinnamoyl ketoamides, possessing an alkyl chain at the α-position, showed potent μ-calpain inhibitory activities indicating that the cinnamoyl skeleton can be regarded as an acyclic variant of calpain inhibitory chromone carboxamide 2. Among synthesized, compound 4e was the most potent inhibitor of μ-calpain (IC₅₀ = 0.13 μM) and also exhibited strong antioxidant activities in DPPH and superoxide anion radical scavenging and lipid peroxidation inhibition assay systems.     

Spirostanol tetraglycosides from Ypsilandra thibetica

Phytochemical reinvestigation on the whole plants of Ypsilandra thibetica obtained five new spirostane glycosides, ypsilandrosides H-L (1-5), and a known saponin polyphylloside III (6). Among them, 1 and 2 are the first spirostane glycosides which possess novel 5(6 → 7) abeo-steroidal aglycones. Compounds 3 and 4 are rare saponins whose aglycones contain a hydroxyl group at C-7. Their structures were elucidated on the basis of MS, 1D and 2D NMR spectroscopic analysis and chemical evidences. The isolated compounds were evaluated for their cytotoxic activity on five tumor cell lines.