کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10594853 | 981852 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Thiazolopyridone ureas as DNA gyrase B inhibitors: Optimization of antitubercular activity and efficacy
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
Scaffold hopping from the thiazolopyridine ureas led to thiazolopyridone ureas with potent antitubercular activity acting through inhibition of DNA GyrB ATPase activity. Structural diversity was introduced, by extension of substituents from the thiazolopyridone N-4 position, to access hydrophobic interactions in the ribose pocket of the ATP binding region of GyrB. Further optimization of hydrogen bond interactions with arginines in site-2 of GyrB active site pocket led to potent inhibition of the enzyme (IC50 2 nM) along with potent cellular activity (MIC = 0.1 μM) against Mycobacterium tuberculosis (Mtb). Efficacy was demonstrated in an acute mouse model of tuberculosis on oral administration.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 3, 1 February 2014, Pages 870-879
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 3, 1 February 2014, Pages 870-879
نویسندگان
Ramesh R. Kale, Manoj G. Kale, David Waterson, Anandkumar Raichurkar, Shahul P. Hameed, M.R. Manjunatha, B.K. Kishore Reddy, Krishnan Malolanarasimhan, Vikas Shinde, Krishna Koushik, Lalit Kumar Jena, Sreenivasaiah Menasinakai, Vaishali Humnabadkar,