ABSTRACT
Neuraminidase (NA) is a promising target for development of anti-influenza drugs. In this study a dihydrofurocoumarin derivative ZINC05577497 was discovered as a lead NA inhibitor based on docking-based virtual screening technique. The optimization of lead ZINC05577497 led to the discovery of a series of novel NA inhibitors 5a-5j. Compound 5b has the most potent activity against NA with IC50 = 0.02 µM, which is lower than those of the reference oseltamivir carboxylate (OSC) (IC50 = 0.04 µM) and ZINC05577497 (IC50 = 0.11 µM). Other target compounds also show potential inhibition of NA activity. Molecular docking results indicate that the good potency of 5b may be attributed to the elongation of the dihydrofurocoumarin ring to the 150-cavity. The results of this paper will be useful to discover more potent NA inhibitors.
Subject(s)
Drug Design , Enzyme Inhibitors/pharmacology , Furocoumarins/pharmacology , Neuraminidase/antagonists & inhibitors , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Furocoumarins/chemical synthesis , Furocoumarins/chemistry , Humans , Molecular Dynamics Simulation , Molecular Structure , Neuraminidase/metabolism , Structure-Activity RelationshipABSTRACT
Hepatocellular carcinoma (HCC) is one of the common malignant tumors with poor overall prognosis. As a tumor suppressor, the function of miR-559 in HCC is not clear. In this study, quantitative real-time PCR was carried out to measure the expression of miR-559 in HCC cell lines. The effects of miR-559 on HCC cell proliferation, migration, and invasion were evaluated through a series of functional assays. The mechanism through which miR-559 regulates HCC cells was investigated by dual-luciferase reporter assay and functional experiments. The results revealed that miR-559 expression was low in HCC cell lines. Upregulation of miR-559 suppressed HCC cell proliferation, migration, and invasion. Dual-luciferase reporter assay confirmed Golgi membrane protein 73 (GP73) as a target gene of miR-559. Moreover, miR-559 could negatively regulate GP73 expression in HCC cells. These results demonstrated that low-level expression of miR-559 was associated with HCC, and overexpression of miR-559 could inhibit HCC cell growth and invasion via targeting GP73.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Membrane Proteins/metabolism , MicroRNAs/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Cell Proliferation/physiology , Gene Expression Regulation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic/physiology , Humans , Membrane Proteins/genetics , MicroRNAs/geneticsABSTRACT
PURPOSE: This study was aimed to analyze the differences of condylar position between the mandibular deviation and the individual normal occlusion. METHODS: Databases of PubMed,Embase,CNKI ,Wanfang ,VIP and CBL were searched for the relevant articles about condylar position with mandibular deviation. The deadline was June 2017.Data quality evaluation and extraction were independently conducted by two authors. Then meta analysis was performed using Rev Man 5.3 software. RESULTS: Six articles on controlled study of the condylar position in patients with mandibular deviation and individuals with normal occlusion were included. 122 patients had mandibular deviation and 110 had normal occlusion. Meta analysis results showed that the condylar superior space[MD=-0.38,95%CI(-0.74,-0.01),P=0.04]and anterior space[MD=-0.72,95%CI(-0.99,-0.04),Pï¼0.00001]of the deviation side in mandibular deviation group were significantly greater than that of the opposite side; The condylar posterior space[MD=-0.35,95%CI(0.25,0.45),Pï¼0.00001]of the deviation side in mandibular deviation group was significantly smaller than that of the opposite side. The condylar posterior space of deviation side[MD=-0.58,95%CI(-0.88,-0.28),P=0.0002],opposite side[MD=-0.30,95%CI(-0.59,-0.00),P=0.05] and the anterior space of opposite side[MD=-0.85,95%CI(-1.58,-0.13),P=0.02] in the mandibular deviation group was significantly smaller than that in the individuals with normal occlusion; the differences were statistically significant. There was no significant difference in the condylar superior space between the deviation side[MD=-0.56,95%CI(-1.14,0.02),P=0.06] and the opposite side[MD=-0.58,95%CI(-1.27,0.10),P=0.10] and the anterior space[MD=-0.05,95%CI(-0.35,0.46),P=0.80]in deviation side in the mandibular deviation group ,comparing with individuals with normal occlusion. CONCLUSIONS: The condylar position of deviation side in patients with mandibular deviation is posterior and inferior, comparing with the opposite side. The condylar position of deviation side in patients with mandibular deviation is posterior, comparing with the individuals with normal occlusion.
