Die Pharmazie. Beihefte最新文献_第3页

Safety, pharmacokinetics and efficacy of donafenib in treating advanced hepatocellular carcinoma: report from a phase 1b trial. 多纳非尼治疗晚期肝细胞癌的安全性、药代动力学和有效性:来自1b期试验的报告

Die Pharmazie. Beihefte Pub Date : 2019-11-01 DOI: 10.1691/ph.2019.9626

Jingrui Liu, Xiaojiao Li, Hong Zhang, Guiling Chen, Hong Chen, Yue Hu, J. Niu, Yanhua Ding

{"title":"Safety, pharmacokinetics and efficacy of donafenib in treating advanced hepatocellular carcinoma: report from a phase 1b trial.","authors":"Jingrui Liu, Xiaojiao Li, Hong Zhang, Guiling Chen, Hong Chen, Yue Hu, J. Niu, Yanhua Ding","doi":"10.1691/ph.2019.9626","DOIUrl":"https://doi.org/10.1691/ph.2019.9626","url":null,"abstract":"Background: Donafenib is a novel compound similar to sorafenib that functions as a multikinase inhibitor. This phase 1b trial aimed to assess the safety, pharmacokinetics and efficacy of donafenib in treating Chinese patients with advanced hepatocellular carcinoma. Methods: From July 2014 to April 2015, 27 eligible advanced hepatocellular carcinoma patients were enrolled in the trial. They were randomly divided into 200 mg and 300 mg bid groups and received these oral doses of donafenib until the appearance of intolerance or disease progression. Results: Overall, donafenib was safe and well tolerated in the two groups, and most adverse events were grade 1 or 2. Elevated transaminase (n=19, 70.4 %), hypocalcemia (n=19, 70.4 %), and skin toxicity (n=17, 63.0 %) were the most frequently encountered adverse events. Donafenib exhibited high variability in pharmacokinetic parameters. Areas under the plasma concentration-time curve from 0-12 h increased disproportionally to the dose escalation. The treatment resulted in partial response in two patients and a stable disease status in 17 patients, and the median time to progression was 120 days for both groups. Conclusion: The results from this phase 1b trial indicate a favorable safety profile and notable anticancer efficacy of donafenib for treating advanced hepatocellular carcinoma. Comparable or better safety and efficacy were observed for a lower dosage of donafenib compared with sorafenib in the literature.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"12 1","pages":"688-693"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86245010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Inhibitory effect of icaritin on proliferation, migration, and invasion of human nasopharyngeal carcinoma cell CNE2 by regulating STAT3 activation. 淫羊藿苷通过调控STAT3激活抑制人鼻咽癌细胞CNE2增殖、迁移和侵袭的作用

Die Pharmazie. Beihefte Pub Date : 2019-11-01 DOI: 10.1691/ph.2019.9632

Xiangdong Li, Chunlei Li, Peiyu Zhou, Shaohua Chen

引用次数: 3

Determination of lovastatin, mevastatin, rosuvastatin and simvastatin with HPLC by means of gradient elution. 梯度洗脱HPLC法测定洛伐他汀、美伐他汀、瑞舒伐他汀和辛伐他汀的含量。

Die Pharmazie. Beihefte Pub Date : 2019-11-01 DOI: 10.1691/ph.2019.8192

S. Marais, J. D. du Preez, L. D. du Plessis, J. du Plessis, M. Gerber

{"title":"Determination of lovastatin, mevastatin, rosuvastatin and simvastatin with HPLC by means of gradient elution.","authors":"S. Marais, J. D. du Preez, L. D. du Plessis, J. du Plessis, M. Gerber","doi":"10.1691/ph.2019.8192","DOIUrl":"https://doi.org/10.1691/ph.2019.8192","url":null,"abstract":"A novel HPLC method with UV detection was developed and validated in skin penetration (in vitro) studies to identify and quantify lovastatin, mevastatin, rosuvastatin and simvastatin. A Venusil XBP C18 (2), 150 x 4.6 mm, 5 μm column (Agela Technologies, Newark, DE) was used with gradient elution (start at 45 % acetonitrile and increase linearly to 90 % after 1 min; hold at 90 % until 6 min and then re-equilibrate at start conditions) and the mobile phase consisted of (A) Milli-Q ® water and 0.1% orthophosphoric acid, and (B) HPLC grade acetonitrile. The flow rate was set at 1 ml/min, 240 nm UV detection and an injection volume of 10 μl. Linearity was obtained over a range of 0.50-200.00 μg/ml and correlation coefficients ranging from 0.998-1.000 were obtained. Average recovery ranged from 95.9-100.6 %. The LOD and LOQ values obtained from the slope of a calibration curve and the standard deviation of the response ranged from 0.0138-0.0860 μg/ml and 0.0419-0.2615 μg/ml, respectively, where lovastatin and simvastatin could be detected at a concentration similar to the other statins, but could only be quantified at a higher concentration than the remaining statins. The specificity of the method was proved as accurate and quantification of statins was found, even within the incorporation of other compounds.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"32 1","pages":"658-660"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82037782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Ginkgolide A protects adverse cardiac remodeling through enhancing antioxidation and nitric oxide utilization in mice with pressure overload. 银杏内酯A通过增强压力过载小鼠的抗氧化和一氧化氮利用来保护不利的心脏重构。

Die Pharmazie. Beihefte Pub Date : 2019-11-01 DOI: 10.1691/ph.2019.9615

W. You, Zhi-ming Wu, F. Ye, Xiang-Qi Wu

{"title":"Ginkgolide A protects adverse cardiac remodeling through enhancing antioxidation and nitric oxide utilization in mice with pressure overload.","authors":"W. You, Zhi-ming Wu, F. Ye, Xiang-Qi Wu","doi":"10.1691/ph.2019.9615","DOIUrl":"https://doi.org/10.1691/ph.2019.9615","url":null,"abstract":"In this study, we aimed to explore whether ginkgolide A (GA) would exhibit cardio-protective effects in mice with pressure overload through enhancing antioxidation and nitric oxide (NO) bioavailability. 21 male mice were randomly assigned into three groups as follows: sham group (10 ml/kg/day PBS, n=7), transverse aortic constriction (TAC) group (TAC and 10 ml/kg/day PBS, n=7) and GA group (TAC and 20 mg/kg/day GA, n=7). All groups received an intraperitoneal injection for four weeks. Heart and body mass were measured. Cardiac function was assessed by echocardiography. The collagen deposition, area of cardiomyocytes, number of capillaries and cell apoptosis were evaluated using Masson's staining, WGA staining, CD31 staining and TUNEL assay, respectively. Cadiac oxidative and antioxidative indexes were measured by colorimetry. Nitrotyrosine (NT) and transforming growth factor-β (TGF-β) were determined by ELISA. Phospho-endothelial NO synthases (eNOS) (Ser1177), phospho-eNOS (Thr 495), eNOS, neuronal NOS (nNOS), inducible NOS (iNOS) and GAPDH were analyzed by western blot. GA treatment greatly improved cardiac dysfunction, suppressed cardiac hypertrophy and increased capillary number at 4 weeks after TAC (P<0.05). Fibrotic area, cardiomyocyte area, and cell apoptosis of GA group were declined notably as compared to those of TAC group (P<0.05). GA administration substantially attenuated cardiac oxidative stress, and reduced NT and TGF-β levels (P<0.05). Besides, GA medication can enhance eNOS signaling, resulting in increased cardiac NO production (P<0.05). GA had a cardioprotective effect in mice with pressure overload, which was closely related with reducing oxidative stress and enhancing NO bioavailability in hearts.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"19 1","pages":"698-702"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88686552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

The influence of viscosity-enhancing agents on oral absorption of drugs. 增粘剂对药物口服吸收的影响。

Die Pharmazie. Beihefte Pub Date : 2019-11-01 DOI: 10.1691/ph.2019.9097

Y. Tanaka, R. Matsubara, K. Furukawa, S. Satonaka, S. Kasaoka

引用次数: 0

Synthesis and cytotoxic evaluation of benzoxazole/benzothiazole-2-imino-coumarin hybrids and their coumarin analogues as potential anticancer agents. 苯并恶唑/苯并噻唑-2-亚胺香豆素复合物及其香豆素类似物的合成及细胞毒性评价。

Die Pharmazie. Beihefte Pub Date : 2019-11-01 DOI: 10.1691/ph.2019.9664

A. Makowska, L. Wolff, F. Sączewski, P. Bednarski, A. Kornicka

{"title":"Synthesis and cytotoxic evaluation of benzoxazole/benzothiazole-2-imino-coumarin hybrids and their coumarin analogues as potential anticancer agents.","authors":"A. Makowska, L. Wolff, F. Sączewski, P. Bednarski, A. Kornicka","doi":"10.1691/ph.2019.9664","DOIUrl":"https://doi.org/10.1691/ph.2019.9664","url":null,"abstract":"Two series of 2-imino-coumarin based hybrids: 3-(benzoxazol-2-yl)-2H-chromen-2-imines 3-9 (series A-I) and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 10-16 (series A-II), as well as their coumarin analogues: 3-(benzoxazol-2-yl)-2H-chromen-2-ones 17-21 (series B-I) and 3-(benzothiazol-2-yl)-2H-chromen-2-ones 22-28 (series B-II) were prepared as potential antitumor agents. The in vitro cytotoxic potency of the synthesized compounds was evaluated against five human cancer cell lines: DAN-G, A-427, LCLC-103H, RT-4 and SISO, and relationships between structure and anticancer activity are discussed. Among the compounds tested, 3-(benzo[d] oxazol-2-yl)-N,N-diethyl-2-imino-2H-chromen-7-amine (6, series A-I) and 3-(benzo[d]thiazol-2-yl)-6-fluoro-2H-chromen-2-one (26, series B-II) exhibited the most potent cytotoxic activity with IC50 values ranging from <0.01 μM to 1.1 μM. In particular, compound 6 demonstrated remarkable cytotoxicity against the A-427 ovarian cancer, the lung cancer LCLC-103H, urinary bladder cancer RT-4 and cervical cancer SISO cell lines with IC50 <0.01-0.30μM, inducing apoptosis in two representative cell lines.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"1 1","pages":"648-657"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91231629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Diosgenin inhibits tumor angiogenesis through regulating GRP78-mediated HIF-1α and VEGF/VEGFR signaling pathways. 薯蓣皂苷元通过调节grp78介导的HIF-1α和VEGF/VEGFR信号通路抑制肿瘤血管生成。

Die Pharmazie. Beihefte Pub Date : 2019-11-01 DOI: 10.1691/ph.2019/9526

H. Cai, Liyan Gong, Jie Liu, Qinfei Zhou, Zengguang Zheng

{"title":"Diosgenin inhibits tumor angiogenesis through regulating GRP78-mediated HIF-1α and VEGF/VEGFR signaling pathways.","authors":"H. Cai, Liyan Gong, Jie Liu, Qinfei Zhou, Zengguang Zheng","doi":"10.1691/ph.2019/9526","DOIUrl":"https://doi.org/10.1691/ph.2019/9526","url":null,"abstract":"The present paper describes the molecular mechanism of diosgenin on tumor microenvironment angiogenesis and the regulation of GRP78 in angiogenesis signaling pathway. CCK8 method was used to evaluate the effect of different concentrations of diosgenin on HUVEC activity in hypoxic microenvironment. Apoptosis was detected by Annexin V/PI staining. Tube Formation experiment was conducted to evaluate angiogenesis. Western Blot assay was applied to detect the expressions and phosphorylation levels of the angiogenesis-related pathways HIF-1α, GRP78, VEGF/VEGFR, PI3K/AKT, ERK, and FAK in rheumatoid HUVEC. Silencing GRP78 by siRNA interference technology was employed to investigate the mechanism of GRP78 involved in the regulation of angiogenesis. The results indicated that diosgenin can significantly inhibit the cell viability of hypoxic HUVEC and the significance is dependent on drug concentration. As the concentration increases, HUVEC activity decreases. Cell apoptosis is induced in a dose-dependent manner and angiogenesis can be significantly inhibited. The hypoxic microenvironment can significantly increase the expressions of HIF-lα, GRP78, VEGF/VEGFR, PI3K/AKT, ERK, FAK proteins in angiogenesis-related pathways, and can also enhance the phosphorylation of AKT, ERK1/2 and FAK proteins, which can be decreased by drug intervention. After silencing GRP78, the angiogenesis-related pathway proteins HIF-lα and VEGF/VEGFR are significantly reduced, thus inhibiting the activation of AKT, ERK1/2, and FAK. The anti-tumor angiogenesis mechanism of diosgenin inhibiting the expression of HIF-lα, GRP78, VEGF/VEGFR, PI3K/AKT, ERK1/2 and FAK signaling pathways may be through multiple pathways and targets, and GRP78 is involved in the regulation of angiogenesis signaling pathway.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"28 1","pages":"680-684"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88789605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Antimicrobial effect of a local release system containing metronidazole against a Porphyromonas gingivalis biofilm. 含甲硝唑局部释放系统对牙龈卟啉单胞菌生物膜的抗菌作用。

Die Pharmazie. Beihefte Pub Date : 2019-11-01 DOI: 10.1691/ph.2019.8241

A. C. S. Ré, M. P. Ferreira, O. Freitas, C. P. Aires

引用次数: 0

N-Acetylglucosamine is the most effective glucosamine derivative for the treatment of membranous nephropathy in rats. n -乙酰氨基葡萄糖是治疗大鼠膜性肾病最有效的氨基葡萄糖衍生物。

Die Pharmazie. Beihefte Pub Date : 2019-11-01 DOI: 10.1691/ph.2019.9733

S. Shebeko, I. Zupanets, O. S. Popov

引用次数: 1

Docosahexaenoic acid inhibits lipopolysaccharide-induced metastatic activities by decreasing inflammation on prostate cancer cell. 二十二碳六烯酸通过降低前列腺癌细胞的炎症来抑制脂多糖诱导的转移活性。

Die Pharmazie. Beihefte Pub Date : 2019-11-01 DOI: 10.1691/ph.2019.9686

Zhengping Wu, Chung-Yi Chen, C. Kao, Yi-Hai Jiang, Chi-Ming Liu

{"title":"Docosahexaenoic acid inhibits lipopolysaccharide-induced metastatic activities by decreasing inflammation on prostate cancer cell.","authors":"Zhengping Wu, Chung-Yi Chen, C. Kao, Yi-Hai Jiang, Chi-Ming Liu","doi":"10.1691/ph.2019.9686","DOIUrl":"https://doi.org/10.1691/ph.2019.9686","url":null,"abstract":"Docosahexaenoic acid (DHA) is rich in fish oil with many pharmacological impacts such as anti-inflammation and anti-cancer activities. In the present study, we aimed to investigate the inhibitory effects of DHA on the invasion and inflammation in prostate cancer cells. The cytotoxicity of DHA with or without lipopolysaccharides (LPS) treatment was evaluated by MTT assay. The invasion and wound healing assays were used to determine the roles of DHA in cell migration and invasion after LPS treatment. The expression levels of IL-6 and IL-8 were detected using ELISA assay. The protein expression was investigated by Western blotting. DHA exhibited significant cytotoxicity at the concentration of 100 μM in PC3 cells. Exposure to DHA (6, 12 and 25 μM) dose-dependently inhibited invasion and wound closure potential in PC3 cells after LPS treatment. DHA dose-dependently downregulated LPS-induced expression levels of IL-6 and IL-8. In addition, the LPS-induced protein levels of p-AKT and COX-2 were suppressed by DHA treatment. Our results indicate that low doses of DHA effectively inhibit metastasis by decreasing IL-6, IL-8, p-AKT and COX-2 expression levels after LPS treatment.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"16 1","pages":"675-679"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72965577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2