Search

Natural triterpenoids, such as oleanolic acid (OA) and hederagenin, display anti-lung cancer effects, and nitric oxide (NO) is associated with some oncogenic signaling pathways. Accordingly, 17 OA/hederagenin-NO donor hybrids were designed, synthesized, and evaluated against tumor cells. The most potent compound, 13, significantly inhibited the proliferation of five tumor cell lines (IC50 4.6-5.2 μM), while hederagenin inhibited the growth of only A549 tumor cells (IC50 > 10 μM). Furthermore, compound 13 showed stronger inhibitory effects on EGFR-LTC kinase activity (IC50 0.01 μM) than hederagenin (IC50 > 20 μM) and inhibited the proliferation of gefitinib-resistant H1975 (IC50 8.1 μM) and osimertinib-resistant H1975-LTC (IC50 7.6 μM) non-small-cell lung cancer (NSCLC) cells. Moreover, compound 13 produced the most NO in H1975 tumor cells, which indicated that NO may play a synergistic role. Collectively, compound 13, a novel hederagenin-NO donor hybrid with a different chemical structure from those of the current FDA-approved EGFR-targeted anti-NSCLC drugs, may be a promising lead compound for the treatment of NSCLC expressing gefitinib-resistant EGFR with a T790 M mutation or osimertinib-resistant EGFR-LTC with an L858R/T790M/C797S mutation. This work should shed light on the discovery of new anti-NSCLC drugs targeting EGFR from natural products.

A novel palladium-catalyzed oxidative three-component coupling of easily accessible N-substituted anthranilamides with isocyanides and arylboronic acids is achieved. This protocol offers an alternative approach toward 2,3-disubstituted quinazolinones with a wide substrate scope and good functional group tolerance.

Six undescribed withanolides were isolated and characterized during the investigation of anti-inflammatory and cytotoxic constituents from the whole plants of Physalis minima L. Their structures were elucidated by extensive spectroscopic analyses (IR, UV, HR-ESI-MS, 1D-NMR, and 2D-NMR), and their anti-inflammatory and cytotoxic activities were evaluated in vitro. All the compounds exhibited anti-inflammatory ability via inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. Moderate cytotoxic activities against A549 lung adenocarcinoma cells, SMMC-7721 hepatic carcinoma cells and MCF-7 breast cancer cells with IC50 values in the range of 40.01–82.17 μM were observed for these withanolides.

The present study was designed to investigate the chemical constituents of the roots of Cudrania fruticosa Wight. Compounds were isolated by various column chromatographic methods including silica gel, polyamide, sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by a combination of 1D and 2D NMR techniques, mass spectrometry, and chemical methods. Two new xanthones, Cudraxanthone T and U (1-2), along with four known compounds (3-6) were isolated from the roots of Cudrania fruticosa Wight.

A new ferulic acid ester named 4-methyl-3-trans-hexenylferulate (1), together with eight known phenolic acid esters (2-9), was isolated from the methanolic extract of the roots and rhizomes of Notopterygium incisium. Their structures were elucidated by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. 4-Methoxyphenethyl ferulate (8) NMR data is reported here for the first time. The uptake and transepithelial transport of the isolated compounds 1-9 were investigated in the human intestinal Caco-2 cell monolayer model. Compounds 2 and 6 were assigned for the well-absorbed compounds, compound 8 was assigned for the moderately absorbed compound, and compounds 1, 3, 4, 5, 7, and 9 were assigned for the poorly absorbed compounds. Moreover, all of the isolated compounds were assayed for the inhibitory effects against nitric oxide (NO) production in the lipopolysaccharide-activated RAW264.7 macrophages model and L-N⁶-(1-iminoethyl)-lysine (L-NIL) was used as a positive control. Compounds 1, 5, 8, and 9 exhibited potent inhibitory activity on NO production with the half maximal inhibitory concentration (IC50) values of 1.01, 4.63, 2.47, and 2.73 μM, respectively, which were more effective than L-NIL with IC50 values of 9.37 μM. These findings not only enriched the types of anti-inflammatory compounds in N. incisum but also provided some useful information for predicting their oral bioavailability and their suitability as drug leads or promising anti-inflammatory agents.

A sensitive and simple high-performance liquid chromatography method with UV detection was developed and validated for determining picroside II in dog plasma. Paeoniflorin was employed as internal standard and the sample pre-treatment procedure consists of deproteinization by addition of acetonitrile. Chromatographic separations were performed on a Shimadzu VP-ODS column (250 x 4.6 mm i.d., 5 microm). The mobile phase consisted of acetonitrile-0.1% acetic acid aqueous (v/v), 23:77, v/v, at a rate of 1 mL/min. Detection was carried out at a wavelength of 266 nm. Calibration standards ranged from 0.25 to 500 microg/mL in dog plasma and the mean correlation coefficient of 0.9981 was found for the linear calibration curves (n = 6). The limit of quantification (LOQ) was 0.25 microg/mL. Intra- and inter-assay RSD ranged from 0.70 to 7.5%. Accuracy (%bias) ranged from -6.3 to 6.0%. This method was applied to the pharmacokinetic study of picroside II in dogs. The study demonstrated the plasma picroside II concentration-time curves were fitted to the two-compartment open model and showed linear pharmacokinetics.

The stereochemistry of two 6, 9-oxygen bridge dibenzocyclooctadiene lignans from Kadsura coccinea, are difficult to separate and very unstable. The present study was designed to develop a high-performance liquid chromatography using circular dichroism detection for the analysis of the stereochemistry. A new 6, 9-oxygen bridge dibenzocyclooctadiene lignans named Kadsulignan Q was firstly found with an S-biphenyl configuration. The other compound was identified as Kadsulignan L with an R- biphenyl configuration. In order to obtain kinetic data on their reversible interconversion, the stability was measured at different deuterated solvents such as deuterated methanol, deuterated chloroform and deuterated dimethylsulfoxide. The lignans were more unstable and converted more easily in deuterated methanol than in deuterated chloroform and deuterated dimethylsulfoxide.

The present study was designed to establish and optimize a new method for extracting chlorogenic acid and cynaroside from Lonicera japonica Thunb. through orthogonal experimental designl. A new ultrahigh pressure extraction (UPE) technology was applied to extract chlorogenic acid and cynaroside from L. japonica. The influential factors, including solvent type, ethanol concentration, extraction pressure, time, and temperature, and the solid/liquid ratio, have been studied to optimize the extraction process. The optimal conditions for the UPE were developed by quantitative analysis of the extraction products by HPLC-DAD in comparison with standard samples. In addition, the microstructures of the medicinal materials before and after extraction were studied by scanning electron microscopy (SEM). Furthermore, the extraction efficiency of different extraction methods and the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of the extracts were investigated. The optimal conditions for extracting chlorogenic acid and cynaroside were as follows: ethanol concentration, 60%; extraction pressure, 400 MPa; extraction time, 2 min; extraction temperature, 30 °C; and the solid/liquid ratio, 1 : 50. Under these conditions, the yields of chlorogenic acid and cynaroside were raised to 4.863% and 0.080%, respectively. Compared with other extraction methods, such as heat reflux extraction (HRE), ultrasonic extraction (UE), and Sohxlet extraction (SE), the UPE method showed several advantages, including higher extraction yield, shorter extraction time, lower energy consumption, and higher purity of the extracts. This study could help better utilize L. japonica flower buds as a readily accessible source of natural antioxidants in food and pharmaceutical industries.

In our research, ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (U-HPLC/Q-TOF-MS) was established for analyzing the metabolite profiles of Danshensu (DSS) in rat feces, bile, urine, plasma and the possible metabolic pathways were subsequently proposed after the oral dose of 80mg/kg; rat biological samples were collected and pretreated by protein precipitation. Then, the samples were injected into an Acquity ultraperformance liquid chromatography BEHC column with mobile phase consisted of acetonitrile (solvent A)-0.1% formic acid-water (solvent B) with a linear gradient elution program. Totally, 17 metabolites of DSS were identified, including 4, 5, 4 and 4 metabolites in the feces, urine, blood, and bile samples respectively. Most of them were to our knowledge reported for the first time. The results indicated that DSS was metabolized via dehydrogenation, deoxygenation, methylation, glucuronidation, and sulfation pathways in vivo. Among these, methylation was considered as the main physiologic processes of it. This study revealed that U-HPLC/Q-TOF-MS was more accurate and sensitive to detect and identify the possible metabolites and to better understand the metabolism of DSS in vivo.

The antiinflammatory activity of five structurally related binaphthaquinones and plumbagin has been studied using a blood platelet aggregation assay. The results suggest that for maximum activity a free hydroxyl peri to the quinoid ring is important. Antiplatelet activity does not correlate with other previously determined biological activity, such as antitumour action, but is consistent with the theory of free radical generation as a mechanism for cytotoxicity and enzyme inhibition but not antiinflammatory activity. © 1998 John Wiley & Sons, Ltd.

A new diterpene, 10-isopropyl-2,2,6-trimethyl-2,3,4,5-tetrahydronaphtha[1,8-bc]oxocine-5,11-diol (1), and a new monoterpene, 6-hydroxy-7-(hydroxymethyl)-4-methylenehexahydrocyclopenta[c]pyran-1(3H)-one, together with four known sesquiterpenes, delta1(10)-aristolene-9beta-ol, debilon, nardosinone, and kanshone A, were isolated from the roots of Nardostachys chinensis. The structures of the new compounds were established on the basis of their spectroscopic data, and the structure of 1 was confirmed by X-ray crystallographic analysis.

The cytotoxic activity of 36 saponins isolated from roots of Pulsatilla chinensis (Bunge) Regel against the human cancer cell lines (A549, SGC-7901) and the human hepatic cell line (HL-7702) was tested by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. Saponins 1–14 showed considerable cytotoxic activity, whereas saponins 15–36 showed no significant activity, which suggested that a free carboxylic group located at C-28 of aglycon is essential for their cytotoxic activity. Moreover, the analysis of structure–activity relationships also suggested that the oleanane-type saponins showed better cytotoxic activity than lupane-type saponins, and the length and linkage of glycolic chain attached to C-3 of aglycon displayed an important effect to the potent cytotoxicity. In conclusion, oleanolic acid 3-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-glucopyranosyl-(1 → 4)]-α-l-arabinopyranoside (5) exhibited the most significant cytotoxic activity.

OBJECTIVE To study the chemical constituents and bacteriostatic activity of Psammosilene tunicoides. METHOD Such methods as silica gel column chromatography and gel column chromatography were adotped separate and purify the compounds, and their structures were indentified on the basis of their spectral data and physicochemical properties. RESULT Ten compounds were separated from ethanol extracts and identified as methyl-4-hydroxybenzoate (1), N-methylsaccharin (2), 3-hydroxy-4-methoxybenzoic acid (3), germanicol (4), tricosanoic acid (5), octacosane (6), amber acid (7), succinic acid (8), stellarine A (9), and oleanane-12-ene-3alpha, 16alpha-two hydroxy-23,28-acid (10). CONCLUSION All compounds except compound 10 were separated from P. tunicoides for the first time. Compounds 8 and 9 showed the bacteriostatic activity to a certain extent.

Two new flavonol glycosides, larycitrin 3- O - α -arabinofuranoside and syringetin 3- O - α -rhamnopyranosyl(1 → 5)- α -arabinofuranoside, together with syringetin and six known flavonol glycosides, kaempferol 3- O - α -arabinofuranoside, myricetin 3-rhamnoside and 3- O -arabinofuranoside, syringetin 3- O - α -arabinofuranoside and 3-rhamnoside, and larycitrin 3-rhamnoside were isolated from the whole plant of Lysimachia congestiflora . All structures were established on the basis of UV, MS and NMR spectral analyses.

The ethyl acetate fraction obtained from the extraction of Artemisia annua yielded 11 flavones, four flavone glycosides and two chromene derivatives. Three new compounds were isolated: quercetagetin 4′-methyl ether, 2,2-dihydroxy-6-methoxychromene and 2,2,6-trihydroxychromene.

Cell suspension cultures developed from Artemisia annua exhibited antimalarial activity against Plasmodium faldparum in vitro both in the n-hexane extract of the plant cell culture medium and in the chloroform extract of the cells. Trace amounts of the antimalarial sesquiterpene lactone artemisinin may account for the activity of the n-hexane fraction but only the methoxylated flavonoids artemetin, chrysoplenetin, chrysosplenol-D and cirsilineol can account for the activity of the chloroform extract. These purified flavonoids were found to have IC50 values at 2.4 - 6.5 × 10(-5)M against P. falciparum in vitro compared with an IC50 value of about 3 × 10(-8)M for purified artimisinin. At concentrations of 5 × 10(-6)M these flavonoids were not active against P. falciparum but did have a marked and selective potentiating effect on the antiplasmodial activity of artemisinin.

Phytochemical studies on aerial parts of Kalanchoe gracilis resulted in the isolation of nine flavonoids and one coumarin. Among the nine flavonoids, four new flavonoids were identified as eupafolin-rhamnosides. The five known compounds were determined as luteolin, quercetin, quercitrin, haempferol, and eupafolin, based on spectroscopic analysis