کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2401492 1102343 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lead selection and characterization of antitubercular compounds using the Nested Chemical Library
ترجمه فارسی عنوان
انتخاب راهنمایی و شناسایی ترکیبات ضدسل با استفاده از کتابخانه مواد شیمیایی تو در تو
کلمات کلیدی
بیماری سل؛ مهار کننده آنزیم؛ هدفمند درمان؛ مهار کننده کیناز؛ غربالگری فنوتیپی
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروبیولوژی و بیوتکنولوژی کاربردی
چکیده انگلیسی

SummaryDiscovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find novel antitubercular agents several approaches have been used in various institutions worldwide, including target-based approaches against several validated mycobacterial enzymes and phenotypic screens. We screened more than 17,000 compounds from Vichem's Nested Chemical Library™ using an integrated strategy involving whole cell-based assays with Corynebacterium glutamicum and Mycobacterium tuberculosis, and target-based assays with protein kinases PknA, PknB and PknG as well as other targets such as PimA and bacterial topoisomerases simultaneously. With the help of the target-based approach we have found very potent hits inhibiting the selected target enzymes, but good minimal inhibitory concentrations (MIC) against M. tuberculosis were not achieved. Focussing on the whole cell-based approach several potent hits were found which displayed minimal inhibitory concentrations (MIC) against M. tuberculosis below 10 μM and were non-mutagenic, non-cytotoxic and the targets of some of the hits were also identified. The most active hits represented various scaffolds. Medicinal chemistry-based lead optimization was performed applying various strategies and, as a consequence, a series of novel potent compounds were synthesized. These efforts resulted in some effective potential antitubercular lead compounds which were confirmed in phenotypic assays.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Tuberculosis - Volume 95, Supplement 1, June 2015, Pages S200–S206
نویسندگان
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