کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1368597 981704 2016 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and docking studies of pyrazine–thiazolidinone hybrid scaffold targeting dormant tuberculosis
ترجمه فارسی عنوان
مطالعات سنتز و دوختن داربست هیبرید پریازیناز تازولیدینون
کلمات کلیدی
بیماری سل، خاموش پیازین، تیازولیدونون، طراحی هیبریدی، داکت
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی

The persistence of Mycobacterium tuberculosis (MTB) in dormant stage assists the pathogen to develop resistance against current antimycobactrial drugs. To address this issue, we report herein the synthesis of N-(4-oxo-2 substituted thiazolidin-3yl) pyrazine-2-carbohydrazide derivatives designed by following the molecular hybridization approach using pyrazine and thiazolidenone scaffolds. The compounds were evaluated against MTB H37Ra and Mycobacterium bovis BCG in dormancy model. Most of the compounds had IC50 values in 0.3–1 μg/ml range. The active compounds were further tested for anti-proliferative activity against THP-1, Panc-1, A549, and MCF-7 cell lines using MTT assay and exhibited no significant cytotoxicity. We also report molecular docking studies using active analogs and MTB – Decaprenylphosphoryl-β-d-ribose-2′-epimerase (DprE1) to rationalize the biological activity and to provide an insight into the probable mechanism of action and binding mode of hybridized structures. The results obtained validate the use of molecular hybridization approach and also suggest that reported compounds can provide a novel pharmacophore to synthesize lead compounds against dormat MTB.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 9, 1 May 2016, Pages 2224–2228
نویسندگان
, , , , , , , , ,