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1.
Quantitative structure-activity relationships (QSAR) have been derived for twenty two 5-benzylidene furanones, pyrrolones and thiophenones having antifungal activity against Candida albicans. The correlation with the parabolic (Hansch) or bilinear (McFarland-Kubinyi) models are superior to those with the linear models (Free-Wilson or Fujita-Ban), while no significant differences exist between the parabolic and bilinear models. Lipophilicity was necessary for good in vitro activity of these compounds. 相似文献
2.
Thierry Humbert Cuong Luu-Duc Michel Comet Pierre Demenge 《European journal of nuclear medicine and molecular imaging》1991,18(11):870-878
Previous studies led us to hypothesize that a fatty acid analogue, 15-p-iodophenyl--methyl pentadecanoic acid (IMPPA or BMIPP), which is taken up but not quickly metabolized by heart cells, would be a more suitable tracer of cellular viability than thallium-201. Biodistribution studies of 1-14C-IMPPA in conscious, freely moving rats showed that the concentration ratio of radioactivity in the heart with respect to the blood was about 8 for at least 60 min after intravenous administration, permitting its use as a putative tracer in these conscious, freely moving rats. Thereafter, the myocardial uptake of14C-IMPPA was studied in isoproterenol-treated rats (daily treatment for 10 days in order to induce cardiac hypertrophy and necrotic foci) with respect to control ones. Comparison of myocardial localizations by quantitative autoradiography of the uptake of201Tl and14C-IMPPA with that of triphenyltetrazolium chloride (TTC) staining enabled comparative evaluation of nutritional blood flow, localization and uptake of14C-IMPPA and necrotic foci size. Distributions of14C-IMPPA and2011 T1 in control rats' hearts were homogeneous, like TTC staining. In infarcted hearts, areas of decreased14C-IMPPA uptake were nearly the same (100%±5%) as those unstained by TTC. These areas were larger than those showing a decrease in thallium uptake (about 70%±5% of the total scar size). Therefore, IMPPA seems to be a more accurate and sensitive indicator of necrosis localization compared with thallium. It may be a useful agent for assessment of myocardial viability by single photon emission tomography (SPET) imaging. 相似文献
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Susan J. Murch Barbara A. Hall Cuong H. Le Praveen K. Saxena 《Journal of pineal research》2010,49(1):95-100
Abstract: Melatonin and serotonin have previously been described in mature wine grapes and finished wines, but the metabolism of these signalling molecules in the development of wine grapes has not previously been investigated. We harvested wine grapes at different stages of development from lag phase through véraison from eight different commercial vineyards representing a diversity of growing conditions, management practices, merlot varietals and localized ecosystems to determine whether different patterns in melatonin and serotonin can be found in wine grapes during seed development and berry maturation. Melatonin was detected in 45% of the fully developed purple, postvéraison grapes but only found in 23% of prelag phase samples. However, the actual concentration of melatonin was highest in wine grapes harvested at the early stage of véraison when the seed is developing. Serotonin was not detected in any of the prelag phase grapes but was consistently detected in 30–35% of grapes harvested during the véraison transition at consistent levels of about 8–10 μg/g. Interestingly, the nitrogen storage compound γ‐aminobutyric acid was also found at about 115 μg/g in 77% of early stage green grapes and declined in both prevalence and concentration with ripening. Together, these data are indicative of a potential role for these molecules in the development and maturation of wine grapes. 相似文献
6.
Joo-Hui Han Yohan Kim Sang-Hyuk Jung Jung-Jin Lee Hyun-Soo Park Gyu-Yong Song Nguyen Manh Cuong Young Ho Kim Chang-Seon Myung 《The Korean journal of physiology & pharmacology》2015,19(5):421-426
The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through G0/G1 to S phase of the cell cycle, as measured by [3H]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G0/G1 phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis. 相似文献
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Expression profile of the telomeric complex discriminates between benign and malignant pheochromocytoma 总被引:2,自引:0,他引:2
Boltze C Mundschenk J Unger N Schneider-Stock R Peters B Mawrin C Hoang-Vu C Roessner A Lehnert H 《The Journal of clinical endocrinology and metabolism》2003,88(9):4280-4286
Telomerase, a ribonucleoprotein complex that includes the telomerase RNA component, the telomerase-associated protein (TP1), the telomerase catalytic subunit (hTERT), and the heat shock protein 90 (HSP90), is closely related to the malignant potential of human tumors. In pheochromocytomas (PC) it is very difficult to predict malignant potential by conventional histology or immunohistochemical and molecular markers. To test whether the expression of telomerase subunits is reflected in the malignant transition of PCs, we determined their mRNA and/or protein expression in 28 benign and nine malignant PCs and compared the results with telomerase activity. RT-PCR analysis revealed that TP1 was ubiquitously expressed. The telomerase RNA component was found in all malignant (100%) and in 13 of 28 (46%) benign PCs. In contrast, hTERT was clearly associated with aggressive biological behavior. All of the malignant (100%), but only two of 28 benign (7%) PCs expressed hTERT. HSP90 was increased in malignant PCs, but was also expressed at a lower level in benign tumors. High telomerase activity was measurable in hTERT-positive tissues only. Our data indicate that hTERT, HSP90, and telomerase activity are up-regulated in malignant cells of the adrenal medulla. The common expression of hTERT and telomerase activity thus represents an additional prognostic marker that may identify more aggressive tumors. 相似文献
9.
P Pévet M Masson-Pévet J Chantegrel A Marsura C Luu-Duc B Claustrat 《The Journal of endocrinology》1989,123(2):243-247
Daily injections of 10 micrograms melatonin in the late afternoon into male golden hamsters kept under a long photoperiod (14 h light: 10 h darkness) and at low ambient temperature 6 +/- 1 degrees C) induced a complete gonadal atrophy after 4 weeks. When administered under the same conditions at doses of 25 micrograms, neither N-(3,5-dinitrophenyl)-5-methoxytryptamine or N-(2,4-dinitrophenyl)-5-methoxytryptamine, a putative melatonin antagonist termed ML-23 in the literature, showed any effect on testicular activity. Moreover, these two drugs were also unable to prevent melatonin-induced gonadal atrophy when injected 30 min before melatonin. The results demonstrate that in the golden hamster and in the present experimental conditions, these drugs do not have the melatonin-antagonistic properties as described in the rat. 相似文献
10.
Ramsay E. Beveridge Heidi Ackerly Wallweber Avi Ashkenazi Maureen Beresini Kevin R. Clark Paul Gibbons Elise Ghiro Susan Kaufman Alexandre Larive Melissa Leblanc Jean-Philippe Leclerc Alexandre Lemire Cuong Ly Joachim Rudolph Jacob B. Schwarz Sanjay Srivastava Weiru Wang Liang Zhao Marie-Gabrielle Braun 《ACS medicinal chemistry letters》2020,11(12):2389
Amino-quinazoline BRaf kinase inhibitor 2 was identified from a library screen as a modest inhibitor of the unfolded protein response (UPR) regulating potential anticancer target IRE1α. A combination of crystallographic and conformational considerations were used to guide structure-based attenuation of BRaf activity and optimization of IRE1α potency. Quinazoline 6-position modifications were found to provide up to 100-fold improvement in IRE1α cellular potency but were ineffective at reducing BRaf activity. A salt bridge contact with Glu651 in IRE1α was then targeted to build in selectivity over BRaf which instead possesses a histidine in this position (His539). Torsional angle analysis revealed that the quinazoline hinge binder core was ill-suited to accommodate the required conformation to effectively reach Glu651, prompting a change to the thienopyrimidine hinge binder. Resulting analogues such as 25 demonstrated good IRE1α cellular potency and imparted more than 1000-fold decrease in BRaf activity. 相似文献