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91.
In the present study, prodrug of ketoprofen was synthesized and evaluated in vitro to optimize the prodrug, and in vivo to observe the reduction in gastrointestinal disturbance and enhanced colonic anti- inflammatory potential for the prodrug. The prodrug was synthesized by coupling ketoprofen with l-glycine (KET-GLY). In vitro reversion of KET-GLY to ketoprofen was carried out in different pHs and in pH 6.8 containing optimized rat fecal material. In vivo healing potential of KET-GLY was evaluated in acetic acid-induced experimental colitis model. In vitro reversion studies suggested that KET-GLY remained intact in stomach but released the free drug at pH 6.8 containing fresh rat fecal material, where the colonic microfloral enzymes (amidase) hydrolyzed the KET-GLY amide linkage, releasing the free drug. In vivo evaluation indicated KET-GLY to be less toxic in stomach, with enhanced anti-inflammatory potential in the colonic region. These findings suggested KET-GLY to be better in action compared with the parent drug. 相似文献
92.
Shailesh D. Shingala G. Venkateswar Reddy R. Sateesh Chandra Kumar P. Ashok Yadav 《Journal of Asian natural products research》2013,15(2):128-135
A total synthesis of guineensine, a secondary metabolite of the Piperaceae family, has been executed in 12 steps with an overall yield of 27%. Key steps in the synthesis featured novel application of a Julia–Kocienski olefination reaction which effectively constructed alkenamide skeleton. This contributes a unique approach to the synthesis of the piperamide alkaloids. 相似文献
93.
目的 研究茄科植物水茄Solanum torvum的化学成分。方法 应用溶剂萃取及柱色谱方法分离水茄的化学成分,通过波谱技术鉴定化合物的结构。结果 从水茄地上全草中分离得到11个化合物,其中有4个酰胺类、4个甾体皂苷类、2个黄酮类、1个有机酸类成分,分别鉴定为N-反式阿魏酸酪酰胺(1)、N-反式-对-香豆酰基酪胺(2)、3-(4-羟基苯基)-N-[2-(4-羟基苯基)-2-甲氧基乙基]丙烯酰胺(3)、N-反式-对-香豆酰基章鱼胺(4)、山柰酚(5)、槲皮素(6)、反式咖啡酸(7)、(25S)-6α-羟基-5α-螺甾烷-3-酮-6-O-(β-D-吡喃鸡纳糖苷)(8)、(25S)-6α-羟基-5α-螺甾烷-3-酮-6-O-[α-L-吡喃鼠李糖基-(1→3)-β-D-吡喃鸡纳糖苷](9)、(25S)-螺甾烷-5-烯-3β-醇-3-O-[β-D-吡喃葡萄糖基-(1→6)-O-β-D-吡喃葡萄糖苷](10)、(25S)-5α-螺甾烷-3β-醇-6α-O-[β-D-吡喃木糖基-(1→3)-β-D-吡喃鸡纳糖苷](11)。结论 化合物3为新的天然产物,化合物1~7为首次从该植物中分得。 相似文献
94.
Carvalho AF Van Bockstaele EJ 《Progress in neuro-psychopharmacology & biological psychiatry》2012,38(1):59-67
The interaction between the endocannabinoid system and catecholaminergic circuits has gained increasing attention as it is recognized that the development of synthetic cannabinoid receptor agonists/antagonists or compounds targeting endocannabinoid synthesis/metabolism may hold some therapeutic potential for the treatment of psychiatric disorders. The noradrenergic system plays a critical role in the modulation of emotional state, primarily related to anxiety, arousal, and stress. Recent evidence suggests that the endocannabinoid system mediates stress responses and emotional homeostasis, in part, by targeting noradrenergic circuits. This review summarizes our current knowledge regarding the anatomical substrates underlying regulation of noradrenergic circuitry by the endocannabinoid system. It then presents biochemical evidence showing an important effect of cannabinoid modulation on adrenergic receptor signaling. Finally, new evidence from behavioral pharmacology studies is provided demonstrating that norepinephrine is a critical determinant of cannabinoid-induced aversion, adding another dimension to how central noradrenergic circuitry is regulated by the cannabinoid system. 相似文献
95.
Bambico FR Hattan PR Garant JP Gobbi G 《Progress in neuro-psychopharmacology & biological psychiatry》2012,38(1):88-96
Preclinical and clinical studies suggest that direct and indirect cannabinoid agonists, including enhancers of endocannabinoids, engender stress-relieving, anxiolytic and antidepressant effects, mediated by central CB(1) receptors (CB(1)Rs). The effect of the main pharmacologically active principle in cannabis, (-)-trans-Δ(9)-tetrahydrocannabinol (delta-9-THC), on depressive behavior and on the serotonin (5-HT) system, which is implicated in the mechanism of action of antidepressants, has not been extensively clarified. Here, we showed that repeated (5 days), but not single (acute) intraperitoneal (ip) treatment with delta-9-THC (1mg/kg) exerts antidepressant-like properties in the rat forced swim test (FST). This effect was CB(1)R-dependent because it was blocked by the CB(1)R antagonist rimonabant (1mg/kg, ip). Using in vivo electrophysiology, we demonstrated that delta-9-THC modulated dorsal raphe (DR) 5-HT neuronal activity through a CB(1)R-dependent mechanism. Acute intravenous delta-9-THC administration (0.1-1.5mg/kg) elicited a complex response profile, producing excitatory, inhibitory and inert responses of 5-HT neurons. Only excitatory responses were blocked by rimonabant. Finally, repeated but not single delta-9-THC administration (1mg/kg, ip) enhanced tonic 5-HT(1A) receptor activity in the hippocampus, a postsynaptic event commonly elicited by standard antidepressants. These results suggest that delta-9-THC, like other CB(1)R agonists and endocannabinoid enhancers, may possess antidepressant properties at low doses, and could modulate 5-HT transmission in the DR and hippocampus as standard antidepressants such as selective serotonin reuptake inhibitors. 相似文献
96.
Wong BS Camilleri M Eckert D Carlson P Ryks M Burton D Zinsmeister AR 《Neurogastroenterology and motility》2012,24(4):358-e169
Background Genetic variation in endocannabinoid metabolism is associated with colonic transit in irritable bowel syndrome (IBS) with diarrhea (IBS‐D). The nonselective cannabinoid (CB) receptor agonist, dronabinol (DRO), reduced fasting colonic motility in nonconstipated IBS. FAAH and CNR1 variants influenced DRO’s effects on colonic motility. Our aims were: (i) to compare dose‐related effects of DRO to placebo (PLA) on gut transit in IBS‐D, and (ii) to examine influence of genetic variations in CB mechanisms on DRO’s transit effects. Methods Thirty‐six IBS‐D volunteers were randomized (double‐blind, concealed allocation) to twice per day PLA (n = 13), DRO 2.5 mg (n = 10), or DRO 5 mg (n = 13) for 2 days. We assessed gastric, small bowel, and colonic transit by validated radioscintigraphy and genotyped the single nucleotide polymorphisms CNR1 rs806378 and FAAH rs324420. Data analysis utilized a dominant genetic model. Key Results Overall treatment effects of DRO on gastric, small bowel, or colonic transit were not detected. CNR1 rs806378 CT/TT was associated with a modest delay in colonic transit at 24 h compared with CC (P = 0.13 for differential treatment effects on postminus pretreatment changes in colonic transit by genotype). No significant interaction of treatment with FAAH rs324420 was detected. Conclusions & Inferences Overall, DRO 2.5 or 5 mg twice per day for 2 days had no effect on gut transit in IBS‐D. There appears to be a treatment‐by‐genotype effect, whereby DRO preferentially delays colonic transit in those with the CNR1 rs806378 CT/TT genotypes. Further study of CB pharmacogenetics may help identify a subset of IBS‐D patients most likely to benefit from CB agonist therapy. 相似文献
97.
Jia G Abaza R Williams JD Zynger DL Zhou J Shah ZK Patel M Sammet S Wei L Bahnson RR Knopp MV 《Journal of magnetic resonance imaging : JMRI》2011,33(3):647-654
Purpose:
To evaluate the capability of amide proton transfer (APT) MR imaging for detection of prostate cancer that typically shows a higher tumor cell proliferation rate and cellular density leading to an MRI‐detectable overall elevated mobile protein level in higher grade tumors.Materials and Methods:
Twelve patients with biopsy‐proven prostate cancer were imaged on a 3 Tesla MR imaging system before prostatectomy. APT‐MR images were acquired by means of a single‐slice single‐shot turbo spin echo sequence with a saturation prepulse preparation using 33 different frequency offsets (?8 to 8 ppm, interval 0.5 ppm). For quantification we used the APT ratio (APTR) based on the asymmetry of the magnetization transfer ratio at 3.5 ppm in respect to the water signal. Tumor and peripheral zone benign regions of interest (ROIs) were delineated based on whole mount pathology slides after prostatectomy.Results:
APTR in prostate cancer ROIs was 5.8% ± 3.2%, significantly higher than that in the peripheral zone benign regions (0.3% ± 3.2%, P = 0.002).Conclusion:
APT‐MR imaging is feasible in prostate cancer detection and has the potential to discriminate between cancer and noncancer tissues. J. Magn. Reson. Imaging 2011;33:647–654. © 2011 Wiley‐Liss, Inc.98.
Akihiro Nishie Yoshiki Asayama Kousei Ishigami Yasuhiro Ushijima Yukihisa Takayama Daisuke Okamoto Nobuhiro Fujita Daisuke Tsurumaru Osamu Togao Koji Sagiyama Tatsuya Manabe Eiji Oki Yuichiro Kubo Tomoyuki Hida Minako Hirahashi‐Fujiwara Jochen Keupp Hiroshi Honda 《Journal of gastroenterology and hepatology》2019,34(1):140-146
99.
培氟沙星C-3(绕丹宁不饱和酮)酰胺的合成及抗肿瘤活性 总被引:2,自引:2,他引:0
为发现将抗菌药氟喹诺酮转化为抗肿瘤药的结构修饰新策略,用酰氨基和绕丹宁不饱和酮分别作为培氟沙星(1)C-3羧基的等排体和修饰基,设计合成了12个新的培氟沙星C-3(绕丹宁不饱和酮)酰胺类目标化合物(6a~6l),其结构经元素分析和光谱数据确证。体外抗增殖活性结果显示,目标化合物对Hep-3B、Capan-1和L1210 3种肿瘤细胞株的活性显著高于母体培氟沙星,含芳杂环或氟苯基化合物的活性与对照抗肿瘤药阿霉素相当。由此推测酰氨基绕丹宁不饱和酮杂合骨架替代C-3羧基有利于提高氟喹诺酮的抗肿瘤活性。 相似文献
100.