کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1396053 1501170 2011 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pharmacophore identification, virtual screening and biological evaluation of prenylated flavonoids derivatives as PKB/Akt1 inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Pharmacophore identification, virtual screening and biological evaluation of prenylated flavonoids derivatives as PKB/Akt1 inhibitors
چکیده انگلیسی

A total of 24 well-defined PKB/Akt1 inhibitors were used to generate pharmacophore models applying Catalyst/HypoGen program. The best ranked model (Hypo_1) was then validated by cost analysis, prediction capability, Cat-Scramble and receiver operating characteristic (ROC) studies. Then, pharmacophore-based virtual screening combined with docking study was performed to search an in-house compound database. Nine preferable hits 75–80, HTS-02143, BTB-14740 and HTS-08006 were prepared and biologically evaluated. Several compounds were identified as good PKB/Akt1 inhibitors, suggesting that Hypo_1 would be reliable and useful in virtual screening. Flow cytometric and western blotting analysis on compounds 79 and 80 further demonstrated that the inhibition of phosphorylation of PKB/Akt1 and its substrates (such as GSK3β) was responsible for their cytotoxic activities.

Pharmacophore-based virtual screening combined with docking studies was performed to search an in-house database. A total of nine preferable hits were selected and biologically assayed. Several compounds were identified as good PKB/Akt1 inhibitors.Figure optionsDownload as PowerPoint slideHighlights
► We established a pharmacophore model of PKB/Akt1 inhibitors using HypoGen program.
► We performed pharmacophore-based virtual screening combined with docking studies.
► Several novel PKB/Akt1 inhibitors were identified and biological evaluated.
► The benzopyran skeleton was firstly found in PKB/Akt1 inhibitors.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 46, Issue 12, December 2011, Pages 5949–5958
نویسندگان
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