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251.
Purification of the apolar extracts of the marine ascidian Phallusia fumigata, afforded two new sulfated sterols, phallusiasterols A (1) and B (2). The structures of the new compounds have been elucidated using mass spectrometry and NMR experiments. The effects of phallusiasterols A and B as modulators of pregnane-X-receptor (PXR) have been investigated. These studies revealed that phallusiasterol A induces PXR transactivation in HepG2 cells and stimulates the expression of the PXR target genes CYP3A4 and MDR1 in the same cell line. Molecular docking calculations suggested the theoretical binding mode of phallusiasterol A with hPXR and revealed that phallusiasterol A fitted well in the LBD of PXR.  相似文献   
252.
In recent years many sterols with unusual structures and promising biological profiles have been identified from marine sources. Here we report the isolation of a series of 24-alkylated-hydroxysteroids from the soft coral Sinularia kavarattiensis, acting as pregnane X receptor (PXR) modulators. Starting from this scaffold a number of derivatives were prepared and evaluated for their ability to activate the PXR by assessing transactivation and quantifying gene expression. Our study reveals that ergost-5-en-3β-ol (4) induces PXR transactivation in HepG2 cells and stimulates the expression of the PXR target gene CYP3A4. To shed light on the molecular basis of the interaction between these ligands and PXR, we investigated, through docking simulations, the binding mechanism of the most potent compound of the series, 4, to the PXR. Our findings provide useful functional and structural information to guide further investigations and drug design.  相似文献   
253.
A subset of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to preferentially reduce the secretion of the highly amyloidogenic, 42-residue amyloid-beta peptide Abeta42. We found that Rho and its effector, Rho-associated kinase, preferentially regulated the amount of Abeta42 produced in vitro and that only those NSAIDs effective as Rho inhibitors lowered Abeta42. Administration of Y-27632, a selective Rock inhibitor, also preferentially lowered brain levels of Abeta42 in a transgenic mouse model of Alzheimer's disease. Thus, the Rho-Rock pathway may regulate amyloid precursor protein processing, and a subset of NSAIDs can reduce Abeta42 through inhibition of Rho activity.  相似文献   
254.
Three dogs diagnosed with aspergillosis developed sinonasal tumors several months after successful treatment with topical clotrimazole solution. Chronic rhinosinusitis was also detected in all cases prior to diagnosis of sinonasal tumors. The inflammatory response to Aspergillus, clotrimazole treatment, and chronic inflammation after treatment are discussed as possible neoplastic promoting factors.  相似文献   
255.
The kinetics of inhibition of human and horse sera butyryl cholinesterases by solanaceous glycoalkaloids α-solanine, α-chaconine and tomatine has been studied by means of a potentiometric biosensor based on pH-sensitive field effect transistors (pH-FETs). Using acetyl- and butyryl choline as substrates, the optimal pH and the apparent kinetic parameters (Kmapp, Vmaxapp) of immobilized cholinesterases have been calculated in the absence of inhibitors. All studied glycoalkaloids were reversible inhibitors of both butyryl cholinesterases, and inhibited the horse and human immobilized enzymes in competitive and mixed modes, respectively. The affinity of each enzyme towards α-solanine, α-chaconine and tomatine has been estimated through calculation of apparent inhibition constants Kiapp and inhibition coefficients I50. An application of the butyryl cholinesterases studied in the biosensors for glycoalkaloids determination in the concentration range of 10−7 to 10−4 M has been discussed.  相似文献   
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