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51.
Identification of Aminoimidazole and Aminothiazole Derivatives as Src Family Kinase Inhibitors 下载免费PDF全文
Dr. Cinzia Maria Francini Dr. Anna Lucia Fallacara Dr. Roberto Artusi Dr. Laura Mennuni Dr. Alessia Calgani Dr. Adriano Angelucci Prof. Silvia Schenone Prof. Maurizio Botta 《ChemMedChem》2015,10(12):2027-2041
Src family kinases (SFKs) are a family of non‐receptor tyrosine kinases (TKs) implicated in the regulation of many cellular processes. The aberrant activity of these TKs has been associated with the growth and progression of cancer. In particular, c‐Src is overexpressed or hyperactivated in a variety of solid tumors and is most likely a strong promoting factor for the development of metastasis. Herein, the synthesis of new 4‐aminoimidazole and 2‐aminothiazole derivatives and their in vitro biological evaluation are described for their potential use as SFK inhibitors. Initially, 2‐aminothiazole analogues of dasatinib and 4‐aminoimidazole derivatives were synthesized and tested against the SFKs Src, Fyn, Lyn, and Yes. Five hits were identified as the most promising compounds, with Ki values in the range of 90–480 nm . A combination of molecular docking, homology modeling, and molecular dynamics were then used to investigate the possible binding mode of such compounds within the ATP binding site of the SFKs. Finally, the antiproliferative activities of the best candidates were evaluated against SH‐SY5Y and K562 cell lines. Compound 3 b [2‐(4‐{2‐methyl‐6‐[(5‐phenylthiazol‐2‐yl)amino]pyrimidin‐4‐yl}piperazin‐1‐yl)ethanol] was found to be the most active inhibitor. 相似文献
52.
Yoshida N Akazawa S Karino T Ishida H Hata Y Katsuragi T Tani Y Takagi H 《Journal of Bioscience and Bioengineering》2007,104(5):424-427
We found 11 genes (FAO1-11) encoding putative oxidoreductases in the Aspergillus oryzae genome, which are similar to fungal fructosyl-amino acid oxidases. The cDNAs corresponding to the genes were cloned and expressed in Escherichia coli. rFao2 had fructosyl-amino acid oxidase activity, whereas rFao1 did not show any enzyme activity, even though the deduced amino acid sequence of Fao1 is identical to that of one of the fructosyl-amino acid oxidase isozymes from Aspergillus oryzae. rFao7 and rFao8 showed oxidase activity toward sarcosine, L-pipecolate, and L-proline. rFao10 was active toward only sarcosine, of the substrates tested. The functions of the other proteins were also predicted from a phylogenetic analysis. 相似文献
53.
Two genes encoding acyl-CoA dehydrogenases, acdA and acdB, arranged in tandem, were found in the chromosomal DNA of Acinetobacter sp. strain M-1. AcdA was purified from the parental strain and AcdB was purified from an Escherichia coli strain expressing the cloned gene. The substrate specificities of the two enzymes suggest that AcdA is a medium-chain acyl-CoA dehydrogenase and that AcdB is a long-chain acyl-CoA dehydrogenase. Characterization of n-alkane metabolism in Acinetobacter sp. strain M-1 has revealed parallel pathways as well as enzymes with overlapping specificities in a single pathway. The two acyl-CoA dehydrogenases described here provide another example of the physiological complexity underlying n-alkane utilization. 相似文献
54.
Brett J West Hisanori Tani Afa K Palu Charles B Tolson C Jarakae Jensen 《Journal of the science of food and agriculture》2007,87(14):2583-2588
BACKGROUND: Noni (Morinda citrifolia L.) leaves have a documented history of food use. However, previous safety and antinutrient studies are absent. The current investigation was conducted to assess the utility of noni leaves as food. RESULTS: No evidence of toxicity or differences in weight gain were observed in acute, subacute, and subchronic oral toxicity tests of ethanol–water (1:1 v/v) and hot‐water extracts of noni leaves in mice at doses of 2000, 200, and 20 mg kg?1 body weight, respectively. Acute systemic anaphylaxis tests of the ethanol–water (4:1 v/v) and hot‐water extracts were negative. Further, leaf proteins were readily digested in simulated gastric fluid. Tannic acid concentrations in frozen and dried leaf were 1.6 and 25.8 g kg?1, respectively. Phytic acid was not detected in the raw leaf (<1 g kg?1). The average oxalic acid content was 1 g kg?1 and was fairly uniform among 22 leaf samples from 11 islands throughout French Polynesia. Similarly, campesterol, stigmasterol, and β‐sitosterol content did not vary widely, suggesting low inter‐island content variability. CONCLUSIONS: The apparent lack of toxicity of the leaves and the hardiness of the plant make it ideal for further agricultural development, especially where sustained growth of other food crops is difficult. Copyright © 2007 Society of Chemical Industry 相似文献
55.
We have constructed new yeast vectors for targeted integration and conditional expression of any sequence at the Saccharomyces cerevisiae TYR1 locus which becomes disrupted. We show that vector integration is not neutral, causing prototrophy for tyrosine and auxotrophy for the vector's selectable marker (uracil or leucine, depending on the vector used). This feature allows a double screening of transformed yeast cells, improving the identification of colonies with the desired chromosomal structure. The GAL10 gene promoter has been added to drive conditional expression of cloned sequences. Using these vectors, chromosomal structure verification of recombinant clones is no longer necessary, since the noise of non-homologous recombination, as well as spontaneous reversion of the selected phenotype, can easily be identified. The ability of the vector to conditionally control gene expression has been confirmed using the gene for the green fluorescent protein (GFP) as a reporter. 相似文献
56.
L Mazzanti P Ambrosetto R Libri R Pascarella A Balsamo G Tani 《Canadian Metallurgical Quarterly》1999,29(1):16-18
OBJECTIVE: To evaluate whether mutation in the exon 10 of the fibroblast growth factor receptor 3(FGFR3) gene in common in Chinese patients with achondroplasia. METHODS: Genomic DNA from seven sporadic cases of achondroplasia was studied by using PCR-SSCP and restriction enzymes. RESULTS: All patients carried the same glycine-to-arginine mutation at codon 380(G380R) of the transmembrane domain of FGFR3. CONCLUSION: The results suggest that the G380R mutation of FGFR3 is also a frequent mutation causing achondroplasia in Chinese. Detecting FGFR 3 gene mutation with PCR-SSCP and restriction enzymes analysis is a convenient, rapid and reliable molecular diagnostic assay for prenatal and early diagnosis of achondroplasia. 相似文献
57.
Alessia Marigo 《Mathematics of Control, Signals, and Systems (MCSS)》2010,22(2):129-153
Limited capacity of communication channels has strongly pushed the analysis of control systems subject to a quantized input
set. Quantized control system of type x
+ = x + u, where the u takes values in a set of 2m + 1 integer numbers, symmetric with respect to 0 arise in some fundamental situations, e.g., flat, nilpotent, and linear
systems with quantized feedback. In this paper we consider this special type of systems and analyze the reachable set after
K steps. We find explicit expressions, for each K and for each m, of m input values such that the reachable set after K steps is as large as possible. 相似文献
58.
59.
An autopsy case of cytokeratin 7-positive minute adenocarcinoma of the lung with systemic metastases
Y Ise H Yanagawa T Hirose K Tani S Yano Y Suzuki E Takeuchi K Maniwa E Shimizu F Ogushi T Sano S Sone 《Canadian Metallurgical Quarterly》1998,37(9):766-769
We describe a 60-year-old woman with leg pain. Although metastatic bone tumor and atypical cells mimicking signet-ring cells in the bone marrow picture were observed, systemic survey revealed no primary lesion. The patient died two months after admission from systemic progress of the disease. Autopsy revealed a small focus of adenocarcinoma within the right upper lobe of the lung and systemic metastases without any particular changes in the gastrointestinal tract. The tumor cells of the lung were diffusely positive for cytokeratin 7, whereas cytokeratin 20 immunoreactivity was weak and focal, and that supported the lung origin of the present tumor. Moreover, the tumor cells in the bone marrow showed a similar pattern in immunoreactivity. These findings suggest that cytokeratin 7 and cytokeratin 20 immunoreactivity is helpful for the premortem diagnosis of the metastatic tumor of unknown origin. 相似文献
60.
K Ohara M Nagai K Tani T Tsukamoto Y Suzuki K Ohara 《Canadian Metallurgical Quarterly》1998,9(7):1291-1294
Alpha 2 adrenergic receptors are thought to play a crucial role in the etiology or treatment of mood disorders. Polymorphism(s) in the promoter region of the alpha 2 receptor may affect the gene expression and be associated with mood disorders. We studied the previously reported polymorphisms of the alpha 2A receptor gene at position-1291 in 114 healthy controls and 103 mood disorder patients. There was statistically no difference between controls and patients in either the genotype or the allele frequency. There was statistically no difference between the genotype and the clinical characteristics. Our results suggest there is no association between this polymorphism in the promoter region of the alpha 2A receptor gene and mood disorders. 相似文献