A new flavone glycoside from Eriocaulon buergerianum / 药学学报

Ten compounds were isolated from the water extract of Eriocaulon buergerianum by HP20, ODS, Sephadex LH-20 and MCI Gel CHP-20 column chromatographic methods. Their structures were identified by spectroscopic and chemical approaches as 6-methoxyquercetin-3-O-(2′′′-vanilloyl)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (1), syringaresinol-4′-O-β-D-glucopyranoside (2), rutin (3), 1-O-feruloylglycerol (4), 1,2-benzenediol (5), vomifoliol (6), β-D-(6-O-trans-feruloyl) fructofuranosyl-α-D-O-glucopyranosied (7), dihydroferulic acid (8), guanosine (9) and quercetin-3-O-β-gentiobioside (10). The compound 1 is a new compound, the compounds 2 and 4-10 were obtained from Eriocaulon genus for the first time, and the compound 3 was isolated from this plant for the first time. Molecular docking study showed that 1 is a potential inhibitor of TNF-α. The compound 1 was evaluated for their anti-inflammatory activities in vitro, and 1 showed significant inhibitory activity against TNF-α production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells at the concentrations of 1, 10 and 100 μmol·L-1.

A new hexenol glycoside from Buddleja officinalis / 中国中药杂志

The chemical constituents of the flower buds of Buddleja officinalis were investigated in this study. Eight compounds were isolated from the water extract of B. officinalis by column chromatography, and their structures were elucidated on the basis of physicochemical properties and spectral data. These compounds were identified as(Z)-hex-3-en-1-ol-1-O-β-D-glucopyranosyl-(1→2)-[β-D-xylcopyranosyl-(1→6)]-β-D-glucopyranoside(1), ebracteatoside B(2), jasmonic acid-11-O-β-D-glucopyranoside(3), 6-hydroxyluteolin-7-O-β-D-glucopyranoside(4), luteolin-7-O-galacturonide(5), vicenin-2(6), decaffeoylverbascoside(7), and 6-O-(E)-feruloyl-D-glucopyranoside(8). Compound 1 is a new 3-hexenol glycoside. Compounds 2, 3, and 6 were isolated from Buddleja genus for the first time, and compounds 4 and 5 were isolated from this plant for the first time.

Complicated intermolecular interactions formed between organofluorine and drug target / 药学学报

Fluorinated compounds, which now make up 20%-25% of all marketed chemical drugs, are playing significant role and showing great potential in medicinal chemistry. Fluorine substitution is always utilized to change the physicochemical properties of the compounds to improve the ADME/T properties. In addition, fluorine substitution leads to improvement of the ligand binding affinity. With respect to molecular level, organofluorine can form various intermolecular interactions with the target proteins, e.g., hydrogen bond, halogen bond, C-F…π interaction, polar interaction and so on. These interactions display unique properties or nature due to the specificity of fluorine atom, which are at the center of attention. This paper reviews the related research background, followed by the research progress of hydrogen bond, halogen bond, C-F…π interaction, polar interaction and some other interactions involved organofluorine.

Research progress in VEGFR-2 inhibitors / 药学学报

Vascular endothelial growth factor receptor (VEGFR-2), a member of the super family of protein tyrosine kinase receptors, plays a vital role in the regulation of tumor metastasis and angiogenesis. Several VEGFR-2 inhibitors have been marketed as antitumor drugs and a range of inhibitors are undergoing clinical or preclinical studies. According to the principle of multi-targeted pharmacolgy, in the field of tumor treatment, nonselective drugs targeting on more than one kinase to inhibit different cell pathways can be more effective than drugs specific for one kinase. Multi-target treatment does not mean abandonment of selectivity, but a precise selectivity for several kinases related to tumor, which is also a big challenge in the development of small molecular antitumor drugs. This paper reviews briefly the advances in research of the VEGFR-2 inhibitors and selectivity strategy in recent years.

Two new sulfated sesquiterpenoids from Petasites tricholobus / 药学学报

Two new sulfated sesquiterpenoids, megastigman-7-ene-3, 5, 6, 9-tetrol-3-O-β-D-6'-sulfonated-glucopyranoside (1) and 3-O-β-D-6'-sulfonated-glucopyranosyl-6-(3-oxo-2-butenylidenyl)-1, 1, 5-trimethylcyclohexan-5-ol (2), along with one known sesquitepenoid compound icariside B1 (3) were isolated from the whole herb of Petasites tricholobus Franch. Their structures were identified by their chemical and spectroscopic characters. All obtained compounds were tested for their cytotoxicity against four cancer cell lines.

Phenolic constituents from Lysimachia patungensis / 药学学报

To study the chemical constituents of Lysimachia patungensis Hand.-Mazz., silica gel column chromatography, reverse phase ODS column chromatography, MCI and Sephadex LH-20, were used to separate the 95% EtOH extract of the whole plant of Lysimachia patungensis Hand.-Mazz.. The structures of the isolated compounds have been established on the basis of chemical and NMR spectroscopic evidence as well as ESI-MS in some cases. Twelve phenolic compounds were obtained and identified as quercetin-3, 3'-di- O-alpha-L-rhamnoside (1), myricetrin (2), quercitrin (3), rutin (4), 2-hydroxynaringenin-4'-O-glucopyranoside (5), naringenin 7-O-glucopyranoside (6), liquiritin apioside (7), licochalcone B (8), tetrahydroxymethoxy chalcone (9), methyl-p-coumarate (10), 2, 4, 6-trihydroxy acetophenone-2-O-glucopyranoside (11) and vaccihein A (12). Among them, compound 1 is a new compound, and compounds 5, 11 and 12 are isolated from the genus Lysimachia L. for the first time, and the others are isolated from the plant for the first time.

Progress of anti-tumor study based on BRAF / 药学学报

BRAF is one of the most important pro-oncogenes, which is mutated in approximately 8% of human tumors. The most common BRAF mutation is a valine-to-glutamate transition (V600E) that is expressed primarily in melanoma, colorectal cancer and thyroid carcinoma. MEK/ERK is constitutively activated in the cells expressing BRAFV600E, leading to tumor development, invasion, and metastasis. Therefore, BRAFV600E is a therapeutic target for melanoma and some other BRAFV600E tumors. Vemurafenib, a BRAFV600E inhibitor, which was approved by FDA for the treatment of late-stage melanoma in 2011, produces improved rates of overall and progression-free survival in patients with the BRAFV600E mutation, making a dramatic breakthrough in melanoma treatment. Vemurafenib is also an individual target drug based on genetic diagnosis. However, its therapeutic success is limited by the emergence of drug resistance. Therefore, it is important to explore the mechanisms underlying the resistance for developing new inhibitor drugs and for preventing or delaying the resistance evolution to BRAF inhibitor drugs. In this review, we described the role of BRAFV600E as an anti-tumor drug target and the development of BRAF inhibitors. We also discussed the mechanisms leading to resistance of BRAFV600E inhibitors. Furthermore, therapeutic strategies that might be employed to overcome acquired resistance were proposed.

Advances in the structure-activity relationship study of natural flavonoids and its derivatives / 药学学报

Flavonoids are a large class of compounds widely distributed in nature. Many pharmacological activities of flavonoids have been reported such as anti-cancer, antioxidant, anti-inflammatory, hepatoprotective, antithrombotic, vasodilator, antiviral, antibacterial, antiallergic, and so on. In recent years, domestic and foreign research groups choose natural flavonoids and optimize their chemical structures in order to develop a number of new derivatives with stronger pharmacological activities. As part of the mechanisms are not clear, we need to strengthen in-depth research in the SAR (structure-activity relationship) study for targeted and efficient structure optimization. This paper systematically summarize current researches in the SAR studies of flavonoids and their derivatives, which can serve as a reference for synthesizing new flavonoid derivatives.

Endostatin in different administration routes combined with adriamycin chemotherapy in the treatment of liver cancer xenograft in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the antiangiogenetic and tumor inhibitory effects of endostatin (Es) by intratumoral versus intravenous administration combined with adriamycin (Adm) for treatment of transplanted tumor in mice.</p><p><b>METHODS</b>Forty mice were subjected to subcutaneous implantation of H22 cells and randomly divided into 4 groups by the body weight when the tumor diameter reached 1 cm, namely the control group (with intratumoral and intravenous injection of normal saline), Es intratumoral group (with intratumoral injection Es and intraperitoneal Adm injection), Es vein group (with intravenous Es injection and intraperitoneal Adm injection), and Adm group (with intratumoral saline injection and intraperitoneal Adm injection). The tumor volumes and tumor inhibition rates were calculated, and the expression of vascular endothelial growth factor (VEGF) and the microvessel density (MVD) of the tumors were examined, with the survival time of the mice also observed.</p><p><b>RESULTS</b>The tumor volume was smaller in Es intratumoral group than in the other groups (P<0.05). The expression of VEGF and M VD in Es intratumoral group was significantly decreased as compared with that in the other groups (P<0.05). The survival time was significantly longer in Es intratumoral group and Es vein group than in the other groups (P<0.05), but showed no significant difference between Es intratumoral group and Es vein group (P>0.05).</p><p><b>CONCLUSION</b>In combination with Adm regimen, Es given intratumoral injection produces better effect than intravenous Es injection against angiogenesis and tumor growth, no significant difference can be found in the survival time between them.</p>

Therapeutic effect of para-toluenesulfonamide on transplanted hepatocarcinoma in nude mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of of percutaneous para-toluenesulfonamide (PTS) injection on transplanted hepatocarcinoma in nude mice.</p><p><b>METHODS</b>Sixty nude mice with subcutaneous transplanted hepatocarcinoma were randomized into 6 groups, namely PTS, chemotherapy, radiotherapy, PTS+chemotherapy, PTS+radiotherapy and control groups. PTS were injected into the tumor in the nude mouse models as indicated, and the tumor growth rate and survival time of the mice were recorded.</p><p><b>RESULTS</b>All the treatments resulted in effective arrest of the tumor growth, but the effects of PTS+chemotherapy and PTS+radiotherapy were more obvious. No significant difference in the survival time of the mice were noted between the groups.</p><p><b>CONCLUSION</b>PTS+chemotherapy and PTS+radiotherapy are safe and reliable, and produces better effects than either radiotherapy or chemotherapy alone.</p>

Advances in the study of berberine and its derivatives / 药学学报

Berberine is a isoquinoline alkaloid extracted from Chinese herbs such as Coptidis rhizome. In the past decade, there are more than 2 000 published papers studying the clinical application, pharmacodynamic mechanism and structure-activity relationship (SAR) of berberine and its derivatives, for treating tumor, diabetes, cardiavascellum disease, hyperlipemia, inflammation, bacterium and virus infection, cerebral ischemia trauma, mental disease, Alzheimer disease, osteoporosis, and so on. These results demonstrate that berberine has wide physiologic function and has great potential for structural modification as new drug lead. However, there is no systematic review about the study of berberine and its derivatives up to now. This paper is a systematic review of the research advances of berberine and its derevatives in clinical application, pharmacodynamic mechanisms, molecular pharmacology, absorption and metabolism, and SAR studies. The current review would provide some useful information for further study on structural modification of berberine for discovering new drug leads based on its pharmacodynamic mechanisms.

Dose-effect relationship of para-toluenesulfonamide for treatment of hepatocellular carcinoma in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the dose-effect relationship of para-toluenesulfonamide (PTS) for treatment of hepatocellular carcinoma in rats.</p><p><b>METHODS</b>Forty-two SD rats bearing subcutaneous transplanted hepatocellular carcinoma were randomly divided into 6 groups (n=7), in which 0.02, 0.04, 0.06, 0.08, and 0.10 ml PTS and 0.10 ml normal saline were injected into the tumor, respectively. All of the rats were executed 24 h after the injection to observe the pathological changes in the tumor.</p><p><b>RESULTS</b>In rats with saline injection, the tumor tissues exhibited no obvious changes and the tumor cells retained the active proliferation. PTS, in contrast, caused coagulation necrosis of the tumor tissue, and the necrotic area expanded with the increase of the injected doses. The necrotic volume of the tumor was in roughly linear correlation with the dose of PTS injected, with the linear regression equation of V (cm(3))=-0.018+2.595Y (where V represents tumor necrosis volume, and Y the injected dose of PTS).</p><p><b>CONCLUSION</b>The dose-effect relationship of PTS is roughly linear, and the PTS dose for injection can be estimated according to the diameter of the tumor.</p>

Association of single nucleotide polymorphism at interleukin-10 gene 1082 nt with the risk of gastric cancer in Chinese population / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the association of single nucleotide polymorphism at interleukin-10 gene 1082 locus with Helicobacter pylori (Hp) infection and the risk of gastric cancer in high prevalent region (Shaanxi Province)aand low prevalence region (Guangdong Province) in China.</p><p><b>METHODS</b>The genomic DNA was extracted from the peripheral blood of 104 healthy individuals, 104 gastric cancer patients from Guangdong Province, and from 102 healthy volunteers and 102 gastric cancer patients in Shaanxi Province, China. The single nucleotide polymorphism at IL-10 gene 1082 locus was analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The serum levels of anit-Hp IgG was measured by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>The frequencies of IL-10-1082 A/A, A/G and G/G genotypes in the 412 subjects were 86.7%, 10.7% and 2.4%, respectively. In the low prevalence region, the number of carriers of IL-10-1082 G* was much greater in the cancer patients than in the healthy controls (14.4% vs 7.7%, Chi2=4.02, P<0.05, OR=1.01, 95% CI=1.08-3.10). The presence of IL-10-1082 G* was associated with significantly increased risk of gastric cancer following Hp infection (Chi(2)=5.36, P<0.05, OR=6.0, 95% CI=1.23-17.52). In the high prevalence region, the frequency of IL-10-1082 G* was slightly higher among the cancer patients than in the healthy controls, but this difference was not statistically significant (12.7% vs 16.6%, P>0.05).</p><p><b>CONCLUSION</b>The G* genotype of IL-10 gene 1082 locus may be associated with increased risk of gastric cancer in China.</p>