Phenylpropanoids from Brachybotrys paridiformis maxim. Ex oliv. And their anti-HBV activities (II).

Five undescribed phenylpropanoids, one undescribed phenolic glucoside, and sixteen known compounds were isolated from Brachybotrys paridiformis Maxim. Ex Oliv. The undescribed compounds were named brachoside B-C, brach acid A-B, brachnan A, and brachin D, respectively. Additionally, the anti-hepatitis B virus activities of all isolated compounds were studied. Among them, brachnan A, brach acid A, globoidnan A, 3-carboxy-6,7-dihydroxy-1-(3',4'-dihydroxy-phenyl)-naphthalene, and 3,4-dihydroxybenzaldehyde showed significant anti-hepatitis B virus activities.

Phenylpropanoids from Brachybotrys paridiformis Maxim. ex Oliv. and their anti-HBV activities.

Using chemical and spectroscopic data, this study on Brachybotrys paridiformis Maxim. ex Oliv. identified four undescribed phenylpropanoids, brachin A-C and brachoside A, together with nine other known compounds. The isolated compounds were tested for anti-hepatitis B virus activities in the HepG2.2.15 cell line. Among them, caffeic anhydride showed the most potent activity.

Bioactive oleanane-type saponins from Hylomecon Japonica.

Six undescribed oleanane-type saponins, named as Hylomeconosides L-Q, were isolated from the whole herb of Hylomecon Japonica, their structures were determined by analysis of 1D and 2D-NMR (1H-1H COSY, HSQC, and HMBC) spectroscopic data, mass spectrometry (HRESI-MS) and chromatographic data (GC and LC). Their structures were identified as 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-galactopyranosyl-(1 â†’ 3)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-L-arabinopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-[α-L-rhamnopyranosyl-(1 â†’ 3)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-[α-L-rhamnopyranosyl-(1 â†’ 3)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-galactopyranoside. Hylomeconosides L-Q showed selective cytotoxicities against human cancer cell lines A549, AGS, HeLa, Huh 7, HT29 and K562. These results represent a contribution to the chemotaxonomy of the saponins of Hylomecon Japonica and their bioactivities.

Studies on isolation and structural identification of saponins from the herb Hylomecon japonica and their bioactivities.

Three undescribed oleanane type triterpenoid saponins (1-3), along with one known saponin (4) were isolated from the whole herb of Hylomecon japonica. Their structures were elucidated by analysis of 1D and 2D-NMR (1H-1H COSY, HSQC, and HMBC) spectroscopic data, mass spectrometry (HR-ESI-MS) and chromatographic date (GC and LC) as 3-O-ß-d-glucopyranosyl-(1 â†’ 2)-ß-d-glucuronopyranosyl gypsogenin 28-O-ß-d-galactopyranosyl-(1 â†’ 3)-[ß-d-xylopyranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-l-arabinopyranosyl ester (1), 3-O-ß-d-galactopyranosyl-(1 â†’ 2)-ß-d-glucuronopyranosyl gypsogenin 28-O-α-l-arabinopyranosyl-(1 â†’ 3)-[ß-d-xylopyranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-l-arabinopyranosyl ester (2), 3-O-ß-d-galactopyranosyl-(1 â†’ 2)-ß-d-glucuronopyranosyl gypsogenin 28-O-ß-d-galactopyranosyl-(1 â†’ 3)-[ß-d-xylopyranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-galactopyranosyl ester (3), 3-O-ß-d-galactopyranosyl-(1 â†’ 2)-[α-l-arabinopyranosyl-(1 â†’ 3)]-ß-d-glucuronopyranosyl gypsogenin 28-O-ß-d-glucopyranosyl-(1 â†’ 3)-[ß-d-xylopyranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-fucopyranosyl ester (4). All saponins possess a partial sequence ß-d-galactopyranosyl-(1 â†’ 2)-ß-d-glucuronopyranosyl at C-3 of the aglycon. Compound 1 has cytotoxic activity against human colon cancer cell lines HT29, 3 against human gastric cancer cell lines AGS, and 4 against human lung cancer cell lines A549, AGS and HT29. Among them, compounds 3 and 4 showed significant inhibitory effect against AGS with IC50 value of 6.01 ± 1.4 µM, 3.66 ± 1.8 µM, respectively. These results represent a contribution to the chemotaxonomy of the saponins of Hylomecon japonica and their bioactivities.

Triterpenoid saponins from the herb Hylomecon japonica.

Six undescribed triterpenoid saponins, named as hylomeconoside C-H, were isolated from the EtOH extract of Hylomecon japonica. On the basis of spectroscopic and chemical evidence, their structures were identified as 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-L-arabinopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-L-arabinopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-[α-L-arabinopyranosyl-(1 â†’ 3)]-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-glucopyranosyl-(1 â†’ 3)-[ß-D-xylopyranosyl-(1 â†’ 4)]-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-L-arabinopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-galactopyranosyl-(1 â†’ 3)-[ß-D-xylopyranosyl-(1 â†’ 4)]-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-fucopyranoside; 3-O-α-L-rhamnopyranosyl-(1 â†’ 3)-[ß-D-galactopyranosyl-(1 â†’ 4)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-galactopyranosyl-(1 â†’ 3)-[ß-D-xylopyranosyl-(1 â†’ 4)]-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-fucopyranoside; 3-O-α-L-rhamnopyranosyl-(1 â†’ 3)-[ß-D-galactopyranosyl-(1 â†’ 4)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside. The 50% EtOH extract showed moderate inhibitory activity on the human cancer cell line HeLa, HepG-2, MCF-7, A549, K562 and TE-1. And these six compounds were tested for cytotoxicity against K562. Among them, hylomeconoside H was found to be the most active on the K562 cell lines (IC50 6.60 µM).

Design, Synthesis and Biological Evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors.

Polymyxins are considered to be the last-line antibiotics that are used to treat infections caused by multidrug-resistant (MDR) gram-negative bacteria; however, the plasmid-mediated transferable colistin resistance gene (mcr-1) has rendered polymyxins ineffective. Therefore, the protein encoded by mcr-1, MCR-1, could be a target for structure-based design of inhibitors to tackle polymyxins resistance. Here, we identified racemic compound 3 as a potential MCR-1 inhibitor by virtual screening, and 26 compound 3 derivatives were synthesized and evaluated in vitro. In the cell-based assay, compound 6g, 6h, 6i, 6n, 6p, 6q, and 6r displayed more potent activity than compound 3. Notably, 25 µΜ of compound 6p or 6q combined with 2 µg·mL-1 colistin could completely inhibit the growth of BL21(DE3) expressing mcr-1, which exhibited the most potent activity. In the enzymatic assay, we elucidate that 6p and 6q could target the MCR-1 to inhibit the activity of the protein. Additionally, a molecular docking study showed that 6p and 6q could interact with Glu246 and Thr285 via hydrogen bonds and occupy well the cavity of the MCR-1 protein. These results may provide a potential avenue to overcome colistin resistance, and provide some valuable information for further investigation on MCR-1 inhibitors.

New Triterpenoid Saponins from the Herb Hylomecon japonica.

Background: Hylomecon japonica, a plant of the Papaveraceae family which is well-known for the alkaloids they produce, is a perennial plant widely distributed in the northeast, central and east regions of China. Although a variety of chemical constituents, including alkaloids, flavonoids, and megastigmoids, have been isolated from H. japonica, the investigation of saponins in H. japonica has not been reported until now. Methods: Various separation techniques, including polyporous resin column chromatography, silica gel column chromatography and hemi-preparative HPLC were applied to the isolation of triterpenoid saponins, and chemical methods such as acid hydrolysis and spectroscopic methods including HRESIMS and NMR were applied to their structure elucidation, and the XTT reduction method was used to assay cytotoxicity. Results: Two new triterpenoid saponins, named hylomeconoside A (1) and B (2) which were identified as 3-O-ß-d-galactopyranosyl-(1→2)-ß-d-glucuronopyranosyl-gypsogenin-28-O-ß-d-xylopyranosyl-(1→3)-ß-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-ß-d-quinovopyranoside (1) and 3-O-ß-d-galactopyranosyl-(1→2)-ß-d-glucuronopyranosyl-gypsogenin-28-O-ß-d-xylopyranosyl-(1→3)-ß-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside (2), and two known triterpenoid saponins identified as dubioside C (3) and lucyoside P (4) on the basis of spectroscopic and chemical evidence, were isolated from H. japonica. Compound 1 exhibited moderate cytotoxicity on MGC-803 and HL-60 cells, with IC50 values of 43.8 and 32.4 µg·mL-1, respectively. Conclusions: Compounds 1 and 2 are new saponins, and 1 is considered to be one of the antitumor principles in this plant. This is the first time that triterpenoid saponins have been isolated from plants of the Papaveraceae family.

Preparative Separation and Purification of the Total Flavonoids in Scorzonera austriaca with Macroporous Resins.

The use of macroporous resins for the separation and purification of total flavonoids to obtain high-purity total flavonoids from Scorzonera austriaca was studied. The optimal conditions for separation and purification of total flavonoids in S. austriaca with macroporous resins were as follows: D4020 resin columns were loaded with crude flavonoid extract solution, and after reaching adsorptive saturation, the columns were eluted successively with 5 bed volumes (BV) of water, 5 BV of 5% (v/v) aqueous ethanol and 5 BV of 30% (v/v) aqueous ethanol at an elute flow rate of 2 BV·h(-1). Total flavonoids were obtained from the 30% aqueous ethanol eluate by vacuum distillation recovery. The content of flavonoid compounds in the total flavonoids was 93.5%, which represents an improvement by about 150%. In addition, five flavonoid compounds in the product were identified as 2″-O-ß-d-xylopyranosyl isoorientin, 6-C-α-l-arabipyranosyl orientin, orientin, isoorientin and vitexin by LC-ESI-MS analysis and internal standard methods. The results in this study could represent a method for the large-scale production of total flavonoids from S. austriaca.

Flavonoid Glycosides and Their Derivatives from the Herbs of Scorzonera austriaca Wild.

Five flavonoid glycosides and two derivatives were isolated from the herbs of Scorzonera austriaca Wild by silica gel column chromatography and preparative HPLC. Their structures were identified, using chemical and spectroscopic methods, as 5,7,4'-trihydroxyflavone 6-C-(2''-O-ß-d-glucopyranosyl ß-d-glucopyranoside) (1), 5,7,3',4'-tetrahydroxyflavone 6-C-(2''-O-ß-d-glucopyranosyl ß-d-glucopyranoside) (2), quercetin 3-O-rutinoside (3), 5,7,4'-trihydroxyflavone 6-C-ß-d-glucopyranoside (4), 3'-methoxy-5,7,4'-trihydroxyflavone 6-C-ß-d-glucopyranoside (5), 5,7,4'-trihydroxyflavone 8-C-(6''-O-trans-caffeoyl ß-d-glucopyranoside) (6), and 5,7,3',4'-tetrahydroxyflavone 8-C-(6''-O-trans-caffeoyl ß-d-glucopyranoside) (7). Compounds 6 and 7 are new flavonoid glycoside derivatives, and compounds 1-5 were isolated from the herbs of Scorzonera austriaca for the first time. Compounds 6 and 7 were also assayed for their hepatoprotective activities with rat hepatocytes in vitro.

Pheonolic Compounds from the Fruits of Viburnum sargentii Koehne.

Seven phenolic compounds were isolated from the fruits of Viburnum sargentii Koehne by silica gel column chromatography and preparative HPLC. On the grounds of chemical and spectroscopic methods, their structures were identified as (-)-Epicatechin (1), 5,7,4'-trihydroxy-flavonoid-8-C-ß-D-glucopyranoside (2), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-α-L-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propane-diol (erythro) (3), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-α-L-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propanediol (threo) (4), (R)-4-hydroxylphenol O-(6-O-oleuropeoyl)-ß-D-glucopyranoside (5), (R)-3-methoxy-4-hydroxylphenol O-(6-O-oleuropeoyl)-ß-D-glucopyranoside (6), quercetin-3-O-rutinoside (7). Compounds 5 and 6 are new monoterpene phenolic glycosides, compounds 1, 3 and 4 were isolated from the Viburnum genus for the first time, and compounds 2 and 7 from the Viburnum sargentii Koehne for the first time. Compounds 1-7 were also assayed for their antioxidant activities with DPPH free radicals.

Isolation and identification of the phenolic compounds from the roots of Sanguisorba officinalis L. and their antioxidant activities.

Four phenolic compounds were isolated from the roots of Sanguisorba officinalis L. by silica gel column chromatography and preparative HPLC. On the basis of chemical and spectroscopic methods, their structures were identified as methyl 4-O-ß-D-glucopyranosy-5-hydroxy-3-methoxylbenzoate (1), 3,3',4'-tri-O-methylellagic acid (2), fisetinidol-(4α-8)-catechin (3), and (+)-catechin (4). Compound 1 is a new phenolic glycoside and compounds 2 and 3 were isolated from the Sanguisorba genus for the first time. Compounds 1­4 were also assayed for their antioxidant activities using the DPPH free radical assay.

Terpene glycosides from the roots of Sanguisorba officinalis L. and their hemostatic activities.

Guided by a hemostasis bioassay, seven terpene glycosides were isolated from the roots of Sanguisorba officinalis L. by silica gel column chromatography and preparative HPLC. On the grounds of chemical and spectroscopic methods, their structures were identified as citronellol-1-O-α-L-arabinofuranosyl-(1→6)-ß-D-glucopyranoside (1), geraniol-1-O-α-L-arabinofuranosyl-(1→6)-ß-D-glucopyranoside (2), geraniol-1-O-α-Larabinopyranosyl-(1→6)-ß-D-glucopyranoside (3), 3ß-[(α-L-arabinopyranosyl)oxy]-19α-hydroxyolean-12-en-28-oic acid 28-ß-D-glucopyranoside (4), 3ß-[(α-L-arabinopyranosyl)-oxy]-19α-hydroxyurs-12-en-28-oic acid 28-ß-D-glucopyranoside (ziyu-glycoside I, 5), 3ß,19α-hydroxyolean-12-en-28-oic acid 28-ß-D-glucopyranoside (6) and 3ß,19α-dihydroxyurs-12-en-28-oic acid 28-ß-D-glucopyranoside (7). Compound 1 is a new mono-terpene glycoside and compounds 2, 3 and 5 were isolated from the Sanguisorba genus for the first time. Compounds 1­7 were assayed for their hemostatic activities with a Goat Anti-Human α2-plasmin inhibitor ELISA kit, and ziyu-glycoside I (5) showed the strongest hemostatic activity among the seven terpene glycosides. This is the first report that ziyu-glycoside Ι has strong hemostatic activity.

Design, synthesis, and in-vivo evaluation of 4,5-diaryloxazole as novel nonsteroidal anti-inflammatory drug.

A series of 4,5-diaryloxazole analogs were designed and the interaction between oxaprozin and cyclooxygenase-2 studied by the docking method to improve the biological activity and reduce the gastrointestinal side effects of oxaprozin. Finally, 3-(4-(4-fluorophenyl)-5-(4-aminosulfonyl-3-fluorophenyl)-oxazole-2-yl) propanoic acid (NC-2142), the best candidate, was selected for synthesis and bioassay based on the screening result. NC-2142 could lower the tumefaction rates of back metatarsus in rats, as well as reduce the writhing times in mice. NC-2142 produced fewer gastric lesions than oxaprozin. After the aminosulfonyl group was introduced into the benzene ring of oxaprozin, its analgesic and anti-inflammatory activities remained unchanged, and it reduced the number of gastric lesions. This provided a feasible method for further structure modification and optimization of oxaprozin.

[Progress in the studies on small molecule IGF-1R inhibitors].

The importance of insulin-like growth factor 1 receptor (IGF-1R) signaling in malignant behaviour of tumour cells is well established. Inhibiting the activity of IGF-1R may result in striking apoptosis in malignant cells growing. IGF-1R antibodies which are currently in phase I and II clinical trials and several IGF-IR TKIs have preclinically been characterized. This review describes recent developments of small molecule tyrosine kinase inhibitors.

Structures of four new triterpenoid saponins from the leaves of Oplopanax elatus Nakai.

AIM: Isolation and structural elucidation of the triterpenoid saponins of Oplopanax elatus Nakai. METHODS: Solvent extraction and column chromatography were used to isolate the triterpenoid saponins, physico-chemical constants and spectroscopic analysis were employed for structural elucidation. RESULTS: Four newtriterpenoid saponins named cirenshenoside S (1), cirenshenoside T (2), cirenshenoside U (3) and cirenshenoside V (4) were isolated, and their structures were elucidated to be 3-O-beta-D-glucopyranosyl 3beta,23-dihydroxylup-20 (29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl (1 --> 4)-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranoside (1), 3-O-beta-D-glucopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4)-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranoside (2), 3-O-beta-D-glucopyranosyl 3beta-hydroxyolean-9(11),12-dien-28-oic acid 28-O-alpha-L-rhamnopyranosyl (1 --> 4)-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranoside (3) and 3alpha-hydroxyolean-12-dien-23,28-dioic acid 28-O-alpha-L-rhamnopyranosyl (1 --> 4 )-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranoside (4), respectively. CONCLUSION: Compounds 1-4 are new triterpenoid saponins and isolated from the leaves of Oplopanax elatus Nakai for the first time.