کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10587626 | 981431 | 2013 | 21 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase
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کلمات کلیدی
PBSMLMBLMNADPHADMESCEHTSSARDMFInhibitor - بازدارندهsister chromatid exchanges - تبادل کروماتید خواهرabsorption, distribution, metabolism and excretion - جذب، توزیع، متابولیسم و دفعdimethylformamide - دی متیل فرمالیدStructure activity relationship - رابطه فعالیت ساختاریBloom syndrome - سندرم بلومHigh throughput screen - صفحه نمایش قدرت بالاPhosphate buffered saline - فسفات بافر شورSmall molecule - مولکول های کوچکmouse liver microsomes - میکروسوم های کبدی موشHomologous recombination - نوترکیبی همولوگnicotinamide adenine dinucleotide phosphate - نیکوتین آمید adenine dinucleotide phosphate
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase](/preview/png/10587626.png)
چکیده انگلیسی
Human cells utilize a variety of complex DNA repair mechanisms in order to combat constant mutagenic and cytotoxic threats from both exogenous and endogenous sources. The RecQ family of DNA helicases, which includes Bloom helicase (BLM), plays an important function in DNA repair by unwinding complementary strands of duplex DNA as well as atypical DNA structures such as Holliday junctions. Mutations of the BLM gene can result in Bloom syndrome, an autosomal recessive disorder associated with cancer predisposition. BLM-deficient cells exhibit increased sensitivity to DNA damaging agents indicating that a selective BLM inhibitor could be useful in potentiating the anticancer activity of these agents. In this work, we describe the medicinal chemistry optimization of the hit molecule following a quantitative high-throughput screen of >355,000 compounds. These efforts lead to the identification of ML216 and related analogs, which possess potent BLM inhibition and exhibit selectivity over related helicases. Moreover, these compounds demonstrated cellular activity by inducing sister chromatid exchanges, a hallmark of Bloom syndrome.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 20, 15 October 2013, Pages 5660-5666
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 20, 15 October 2013, Pages 5660-5666
نویسندگان
Andrew S. Rosenthal, Thomas S. Dexheimer, Opher Gileadi, Giang H. Nguyen, Wai Kit Chu, Ian D. Hickson, Ajit Jadhav, Anton Simeonov, David J. Maloney,