Five new flavonol glycosides (1, 3, 5—7) were isolated from the aerial parts of Epimedium pubescens MAXIM., along with two known compounds, sagittasine C (2) and 4′,5-dihydroxyl-8-(3,3-dimethylallyl)-flavonol 3-O-[β-D-xylopyranosyl(1→3)-4-O-acetyl-α-L-rhamnopyranoside]-7-O-β-D-glucopyranoside (4). The structures were elucidated on the basis of their 1D-, 2D-NMR, MS, UV and IR spectra data.
A high-performance liquid chromatographic-mass spectrometric method was developed for the simultaneous determination of 10 flavonoids in Viscum coloratum obtained from different host species and different sources. Viscum coloratum was extracted with 50% methanol. The extracts were separated on a C18 column with a gradient of 0.1% (v/v) formic acid and methanol. The flavonoids in the extracts were detected by negative electrospray ionization mass spectrometry in selective ion monitoring mode. The calibration curves showed good linearity (r>0.998) within the test ranges (homoeriodictyol: 0.149—8.940 μg/ml, homoeriodictyol-7-O-β-D-glycoside: 0.230—13.80 μg/ml, homoeriodictyol-7-O-β-D-apiose (1→2)-β-D-glycoside: 5.000—300.0 μg/ml, homoeriodictyol-7-O-β-D-apiose (1→5)-β-D-apiose (1→2)-β-D-glycoside: 0.835—125.3 μg/ml, rhamnazin-3-O-β-D-glucoside: 0.064—3.840 μg/ml, rhamnazin-3-O-β-D-(6″-β-hydroxy-β-methyglutaryl)-glucoside: 1.435—86.10 μg/ml, isorhamnetin-3-O-β-D-glucoside: 0.930—55.80 μg/ml, 5-hydroxy-3,7,3′-trimethoxyflavone-4′-O-β-D-glucoside: 0.067—4.020 μg/ml, 5,7,4′-trihydroxy-3,3′-dimethoxyflavone: 0.270—16.20 μg/ml, pachypodol: 0.110—6.600 μg/ml). The limits of quantification were between 0.006—0.720 μg/ml. The assay was reproducible and the overall intra- and inter-day variations were less than 4.6%. The recoveries varied from 93.4 to 103.9% at three different concentration levels. The validation method was used to determine the contents of 10 flavonoids in Viscum coloratum. A one-way analysis of variance was applied to evaluate Viscum coloratum-host-source interactions. Compared with the host species, the sample source had a significant impact on the sample content.
To facilitate effective resource utilization, we have investigated triterpene saponins such as saikosaponin from the aerial parts of Bupleurum (B.) falcatum L., which are commonly discarded. Seven oleanene saponins were isolated from this plant; they were classified as the 13,28-epoxy type, 12-ene type, 9(11),12-diene type, and 28-acid type on the basis of their structural characteristics. For comparison, we also examined the oleanene saponins of the seeds of B. falcatum and the aerial parts of B. rotundifolium L. to obtain seven saponins and one sapogenol from the former and thirteen oleanene saponins from the latter. Several compounds obtained from them were investigated for their hepatoprotective activity and hepatotoxicity. The 13,28-epoxy type saponins had hepatoprotectivity. Ursane type showed hepatotoxicity from middle concentration. The 11,13(18)-diene type saponins did not express hepatoprotective activity. The 28-acid type saponin which has a glucosyl carboxy group showed hepatoprotective action.
Garlicnin A (1), a new stable, sulfur-containing compound isolated from a fraction of the acetone extracts of Allium sativum L. garlic bulbs, showed the potential to suppress tumor cell proliferation by inhibiting the polarization of M2 alternatively activated macrophages, and its structure was characterized as 3,4-dimethyl-5-(4,5-dithia-1E,7-octadiene)-tetrahydrothiophene-2-sulfoxide-S-oxide, on the basis of the results of spectroscopic analysis results.
Four new neolignans, marphenols G—J (1—4), together with two known ones, were isolated from the leaves and stems of Schisandra wilsoniana. The structures of 1—4 were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. New compounds 1—4 were tested for their anti-human immunodeficiency virus (HIV)-1 activities and they showed weak bioactivities.
Three new norlanostane-type triterpene glycosides, scillanostasides A, B, and C, and two new lanostane-type triterpene glycosides, scillanostasides D and E, were isolated from the bulbs of Scilla scilloides DRUCE (Liliaceae) along with one known norlanostane-type triterpene heptaglycoside, scillascilloside G-1. Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence.
Photochemical bond-cleavage reactions are potentially useful in chemistry, bioorganic chemistry and medicinal chemistry. We previously reported on a photochemical cleavage reaction of 8-quinolinyl sulfonate (8-QS) derivatives in aqueous solution at neutral pH, which we proposed to proceed via an excited triplet state. In this report, we report on the synthesis of some new photocleavable 8-QS derivatives, in which halogen atoms or a nitro group was introduced at the 7-position, in an attempt to improve photoreactive properties and to produce a red-shift in the irradiation wavelength. The introduction of bromine and iodine resulted in an acceleration in the photoreaction by about 1.5 times, possibly due to a heavy atom effect. It was also found that 7-nitro-8-QS absorbs at >360 nm, and, as a result, the S–O bond of this compound can be cleaved by photoirradiation with a fluorescent lamp in aqueous solution and on silicon surface.
In continuation of our previous work, a novel series of steroid derivatives were synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic properties were evaluated. Twenty-one heterocyclic derivatives containing a cyanopyrane ring fused to a steroidal moiety were conveniently synthesized and screened for their antagonistic, antiandrogen and prostate anticancer activities comparable to that of bicalutamide as the reference control. Some of the compounds exhibited better antagonistic, antiandrogen and prostate anticancer activities than the reference controls. Initially the acute toxicity of the compounds was assayed via the determination of their LD50. Synthetic steroidal structures fused to a substituted cyanopyrane ring seem to be a promising approach in the search for novel leads for potent antagonistic, antiandrogen and prostate anticancer agents.
As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti-atherosclerotic agents, we recently reported the discovery of the (4-phenylcoumarine)acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl]-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs.
We synthesized and evaluated inhibitory activity against T-type Ca2+ channels for a series of 1-alkyl-N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]piperidine-4-carboxamide derivatives. Structure–activity relationship studies have revealed that the isopropyl substituent at the benzylic position plays an important role in exerting potent inhibitory activity, and the absolute configuration of the benzylic position was found to be opposite that of mibefradil, which was first launched as a new class of T-type Ca2+ channel blocker. Oral administration of N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]-1-[2-(3-methoxyphenyl)ethyl]piperidine-4-carboxamide (17f) lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, an adverse effect often caused by traditional L-type Ca2+ channel blockers.
Histone deacetylase inhibitor (HDACI), suberoylanilide hydroxamic acid (SAHA), approved by the Food and Drug Administration (FDA) for the treatment of cutaneous T cell lymphoma, is a promising new treatment strategy for various cancers. In this study, we hypothesized that a liposomal formulation of HDACI might efficiently deliver HDACI into tumors. To incorporate HDACI efficiently into the liposomal membrane, we synthesized six HDACI-lipid conjugates, in which polyethylene glycol2000 (PEG2000)-lipid or cholesterol (Chol) was linked with a potent hydroxamic acid, HDACI, SAHA or K-182, by cleavable linkers, such as ester, carbamide and disulfide bonds. Liposomal HDACI-lipid conjugates were prepared with distearoylphosphatidylcholine (DSPC) and HDACI-Chol conjugate or with DSPC, Chol and HDACI-PEG-lipid conjugates, and their cytotoxicities were evaluated for human cervix tumor HeLa and mouse colon tumor Colon 26 cells. Among the liposomes, liposomal oleyl-PEG2000-SAHA conjugated with SAHA and oleyl-PEG2000via a carbamate linker showed higher cytotoxicity via hyperacetylation of histone H3 and induction of caspase 3/7 activity. These results suggested that liposomal HDACI-lipid conjugates may be a potential tool for cancer therapy.
Two new flavone C-glycosides, trollisin A (1) and trollisin B (2), along with seven known flavonoids, isoswertisin (3), isoswertiajaponin (4), orientin (5), 2″-O-β-L-galactopyranosylvitexin (6), 2″-O-β-L-galactopyranosylorientin (7), neodiosmin (8) and acacetin-7-O-neohesperidoside (9) were isolated from the flowers of Trollius ledebourii REICHB. The structures of the new compounds were elucidated based on spectral analysis, including MS, 1D- and 2D-NMR experimentation.
The MeOH extract from the whole plants of Sambucus adnata has shown significant protein–tyrosine phosphatase 1B (PTP1B) inhibitory activity. Chemical study on the extract resulted in the isolation of thirteen compounds, including a novel triterpene (1). The structure of 1 was determined to be 1α,3β-dihydroxy-urs-12-en-11-one-3-yl palmitate on the basis of extensive spectroscopic analyses. Among the isolated compounds, ursolic acid, oleanolic acid and (±)-boehmenan showed the most potent PTP1B inhibitory activity in vitro with the IC50 values of 4.1, 14.4 and 43.5 μm, respectively. The kinetic analysis indicated that (±)-boehmenan inhibits PTP1B activity in a competitive manner.
In this study, we investigated the surface properties of raw wheat bran (R-WB) and wheat bran treated with Pectinase PL (P-WB) to evaluating its efficacy for removal of cadmium from waste water. The concentration of cadmium ions adsorbed by them was evaluated. The concentration of carboxyl groups of R-WB (3.56 mmol/g) was greater than that of P-WB (2.11 mmol/g), which indicated that the pectin of R-WB was broken down, resulting in a decrease in the concentration of carboxyl groups due to the enzyme treatment. From the scanning electron microscope (SEM) images of P-WB, the pores were newly generated with enzyme treatment. The concentration of cadmium ions adsorbed onto R-WB was greater than that of cadmium ions adsorbed onto P-WB. These results show that the adsorption mechanism of cadmium ions onto R-WB and P-WB depends on the carboxyl groups of pectin.
A new solanocapsine-type tomato glycoside, a novel and interesting natural steroidal glycoside, was isolated from a mini tomato, Solanum lycopersicum L. The chemical structure of the new minor glycoside, esculeoside B-5 (3), was determined to be (5S,22R,23S,24R,25S)-22,26-epimino-16β,23-epoxy-3β,23,24-trihydroxycholestane 3-O-β-lycotetraoside.
In the conventional method of mixer blending extraction, the yields of the tomato-saponin, esculeoside A, in the mini and middy tomatoes were found to be 0.043% and 0.046%, respectively. In order to improve the yields, we attempted a more efficient extraction using shock waves. The yields of esculeoside A were 0.0987% in air after 1 shock, 0.0792% in air after two shots, 0.0648% in half water after 1 or 2 shocks, and 0.0599% in water after 1 or 2 shocks. The yields obtained by the proposed method were approximately twice those of the conventional mixer blending method; therefore, this method is regarded to be very efficient. Moreover, two spirosolane glycosides, tomatine and lycoperoside A, were obtained for the first time from the ripe tomato fruit in this method. To date, these compounds have not been obtained with the mixer blending method. However, whether these glycosides are produced from esculeoside A or are newly extracted from the plant organ by the shock wave is still unclear.
Two new cannabinoid-like chromane and chromene derivatives named anthopogocyclolic acid (1) and anthopogochromenic acid (2) and five related compounds (3—7) which are known as synthetic analogues of cannabinoids: cannabichromene (CBC) type, cannabicyclol (CBL) type, and cannabicitran (CBT) type, have been isolated together with geranyl orsellinic acid (8) from the Chinese medicinal plant Rhododendron anthopogonoides. Their structures were elucidated based on spectroscopic and chemical evidence. The absolute configuration of the asymmetric carbons at C-2 of 1—7 was determined to be S from their circular dichroism (CD) spectra. Compounds 2, 4 and 6 inhibited compound 48/80-induced histamine release from rat peritoneal mast cells.
A series of 5-phenyl-4,5-dihydro-1,3,4-thiadiazoles were synthesized and their cytotoxicity was examined against four human cancer cell lines, e.g. lung cancer (A549), ovarian cancer (SK-OV-3), skin cancer (SK-MEL-2), and colon cancer (HCT15). The title compounds were synthesized by condensation of thiosemicarbazide with substituted benzaldehydes, followed by cyclization with acetic anhydrides in good yields. Most of the compounds exhibited significant suppressive activity against the growth of all of the cancer cell lines. The 4-hydroxy analogue of 5-phenyl-4,5-dihydro-1,3,4-thiadiazole (2h) was most active in the inhibition of growth of the SK-MEL-2 cell line, with an IC50 value of 4.27 μg/ml; followed by compound 2a (IC50 5.16 μg/ml). The compounds 2j, 2h, and 2b, bearing 3-methoxy-4-hydroxy-, 4-hydroxy- and 4-methyl substituents in the C-5 phenyl ring respectively, exhibited the highest activity against the SK-OV-3 (IC50 7.35 μg/ml), HCT15 (IC50 8.25 μg/ml) and A549 (IC50 9.40 μg/ml) cell lines, respectively. A structure–activity relationship study revealed that an optimal electron density on the C-5 phenyl ring of 1,3,4-thiadiazoles is crucial for their cytotoxic activity against the human cancer cell lines used in the present study.
Ten oleanane-type saponins (1—10), including three new compounds, namely bifinosides A—C (1—3), were isolated from the roots of Panax bipinnatifidus SEEM. Their structures were elucidated on the basis of chemical and spectroscopic methods.
Two new secolignans and one new neolignan, named feddeiphenols A—C (1—3), together with eight known compounds (4—11), were isolated from the leaves and stems of Daphne feddei. Their structures were established on the base of spectroscopic methods, mainly extensive NMR, UV spectroscopy, and MS spectrometry. Compounds 1—11 were tested for their anti-human immunodeficiency virus (HIV)-1 activity and cytotoxicity. The results revealed that compounds 1, 2, 3, 7, and 9 showed therapeutic index (TI) values above 30, respectively, and the other compounds also showed weak anti-HIV-1 activity. Compound 1 showed modest cytotoxic activity. The other compounds also showed weak cytotoxic activity.
Two new lignans, termed pharsyringaresinol (1) and pharbilignoside (2), a new phenylethanoid glycoside, termed pharbiniloside (3), and 22 known compounds, were isolated from the ethanol extract of the seeds of Pharbitis nil. The structures of the new compounds (1—3) were determined on the basis of spectroscopic analyses, including 2D-NMR and circular dichroism (CD) spectroscopy studies. Among the isolates, compounds 2, 11, 12, and 24 exhibited significant cytotoxicity against human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) with IC50 values ranging from 8.07 to 28.30 μM. In addition, compounds 11, 12 and 24 potently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, a microglia cells with IC50 values ranging from 14.7 to 19.9 μM.
Three new sesquiterpenes were isolated from the fermentation broth of Streptomyces sp. and their structures were determined as caryolane-1,7α-diol (1), 1,6,11-eudesmanetriol; (1α,6β)-form (2), 11-eudesmene-1,6-diol; (1α,6β)-form (3), together with nine known compounds as caryolane-1,9α-diol (4), 2-methyl-5-nonanol (5), soyasaponin I (6), cyclo (Ala-Leu) (7), homononatinic acid (8), β-sitosteryl glucoside-3′-O-heptadecoicate (9), 2′-deoxythymidine (10), 2′-deoxyuridine (11), trehalose (12). The structures were elucidated by spectral analysis.