67 research outputs found
Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells
BACKGROUND: Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and PKD by curcumin causes stabilization of the tumor suppressor p53. It has been shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun steady state levels in HeLa cells. The aim of this work was to search for new CSN kinase inhibitors analogue to curcumin and emodin by means of an in silico screening method. METHODS: Here we present a novel method to identify efficient inhibitors of CSN-associated kinases. Using curcumin and emodin as lead structures an in silico screening with our in-house database containing more than 10(6 )structures was carried out. Thirty-five compounds were identified and further evaluated by the Lipinski's rule-of-five. Two groups of compounds can be clearly discriminated according to their structures: the curcumin-group and the emodin-group. The compounds were evaluated in in vitro kinase assays and in cell culture experiments. RESULTS: The data revealed 3 compounds of the curcumin-group (e.g. piceatannol) and 4 of the emodin-group (e.g. anthrachinone) as potent inhibitors of CSN-associated kinases. Identified agents increased p53 levels and induced apoptosis in tumor cells as determined by annexin V-FITC binding, DNA fragmentation and caspase activity assays. CONCLUSION: Our data demonstrate that the new in silico screening method is highly efficient for identifying potential anti-tumor drugs
A seven- to 14-year follow-up study of bipolar hip arthroplasty in the treatment of osteonecrosis of the femoral head
The Contribution of Water to the Specific Heat Change at the Glass-to-Rubber Transition of the Ternary System BSA-Water-NaCl
Case files of the Drexel University medical toxicology fellowship: Methadone-induced QTc prolongation
Modelling Knee Range of Motion Post Arthroplasty: Clinical Applications
Purpose: To model change in knee range of motion (ROM) post total knee arthroplasty (TKA) and to show how this information can be incorporated into clinical decision making
Site-directed mutagenesis of human papillomavirus 18 promoter elements and tissue-specific expression in cervical carcinoma cells
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