کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10584190 | 981326 | 2013 | 45 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Design and synthesis of l- and d-phenylalanine derived rhodanines with novel C5-arylidenes as inhibitors of HCV NS5B polymerase
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Design and synthesis of l- and d-phenylalanine derived rhodanines with novel C5-arylidenes as inhibitors of HCV NS5B polymerase Design and synthesis of l- and d-phenylalanine derived rhodanines with novel C5-arylidenes as inhibitors of HCV NS5B polymerase](/preview/png/10584190.png)
چکیده انگلیسی
Hepatitis C virus (HCV) NS5B polymerase is a key target for anti-HCV therapeutics development. Herein, we report the synthesis and in vitro evaluation of anti-NS5B polymerase activity of a molecular hybrid of our previously reported lead compounds 1 (IC50 = 7.7 μM) and 2 (IC50 = 10.6 μM) as represented by hybrid compound 27 (IC50 = 6.7 μM). We have explored the optimal substituents on the terminal phenyl ring of the 3-phenoxybenzylidene moiety in 27, by generating a set of six analogs. This resulted in the identification of compound 34 with an IC50 of 2.6 μM. To probe the role of stereochemistry towards the observed biological activity, we synthesized and evaluated the d-isomers 41 (IC50 = 19.3 μM) and 45 (IC50 = 5.4 μM) as enantiomers of the l-isomers 27 and 34, respectively. The binding site of compounds 32 and 34 was mapped to palm pocket-I (PP-I) of NS5B. The docking models of 34 and 45 within the PP-I of NS5B were investigated to envisage the molecular mechanism of inhibition.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 11, 1 June 2013, Pages 3262-3271
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 11, 1 June 2013, Pages 3262-3271
نویسندگان
Bhargav A. Patel, Ramalingam Krishnan, Nikhil Khadtare, K.R. Gurukumar, Amartya Basu, Payal Arora, Aaditya Bhatt, Maulik R. Patel, Dibyendu Dana, Sanjai Kumar, Neerja Kaushik-Basu, Tanaji T. Talele,