کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1357975 981306 2015 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Exploring the gyrase ATPase domain for tailoring newer anti-tubercular drugs: Hit to lead optimization of a novel class of thiazole inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Exploring the gyrase ATPase domain for tailoring newer anti-tubercular drugs: Hit to lead optimization of a novel class of thiazole inhibitors
چکیده انگلیسی

Gyrase ATPase domain, the pharmaceutical underexploited segment of DNA gyrase, the sole Type II topoisomerase present in Mycobacterium tuberculosis represents an attractive target for anti-tubercular drug discovery. Here we report, the development of a novel series of MTB DNA gyraseB inhibitor identified through a medium throughput screening (MTS) of BITS in-house chemical library (3000 compounds). The MTS hit was further remodeled by chemical synthesis to identify the most potent analogue 27 exhibiting an in vitro gyrB inhibitory IC50 of 0.15 μM. The series also demonstrated well correlating gyrase super coiling activity and in vitro anti-mycobacterial potency against MTB H37Rv strain. Furthermore the compounds displayed good safety profile in their subsequent cytotoxicity and hERG toxicity evaluations, to be worked out from a pharmaceutical point of view as potential anti-tubercular agents.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 23, Issue 3, 1 February 2015, Pages 588–601
نویسندگان
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