کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10129210 | 1645202 | 2018 | 47 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structure based identification and biological evaluation of novel and potent inhibitors of PCAF catalytic domain
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
p300/CBP Associated Factor (PCAF), a GNAT family member protein, represent a valid target for therapeutic interventions since its dysfunction has implicated in variety of diseases like cancer, diabetes, inflammatory diseases, etc. Despite its potential for therapeutics, only a small number of PCAF inhibitors were reported. Hence, in this study, the catalytic domain of PCAF was explored to screen novel, potent and cell permeable inhibitor from three small molecule databases like Life Chemical, Maybridge and Chembridge by using Structure Based Virtual Screening (SBVS) method. Further, Induced Fit Docking, Binding Free Energy calculation, Single Point Energy calculation and Molecular Dynamics Simulation were performed on selected hits. In silico results revealed that F2209-0381 has higher binding energy of â109.722 and have greater cell permeability (QPPCacoâ¯=â¯1456.764; QPPMDCKâ¯=â¯742.941) than rest of hits. Cytotoxicity effect and protein expression analysis of F2209-0381 on A549 cells reveals that it exhibited strong inhibition with IC50 value of 58.31â¯Î¼g/ml and significantly reduced the expression of PCAF after 72â¯h time point. Thus, this study warrants that F2209-0381 could become a novel, potent and cell permeable drug of PCAF thereby it could combat its mediated diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 120, Part A, December 2018, Pages 823-834
Journal: International Journal of Biological Macromolecules - Volume 120, Part A, December 2018, Pages 823-834
نویسندگان
Venkatesan Suryanarayanan, Tamilselvam Rajavel, Kasi Pandima Devi, Sanjeev Kumar Singh,