کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10588564 | 981474 | 2010 | 35 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 18, 15 September 2010, Pages 6822-6856
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 18, 15 September 2010, Pages 6822-6856
نویسندگان
Robert P. Sellers, Leslie D. Alexander, Victoria A. Johnson, Chun-Chieh Lin, Jeremiah Savage, Ricardo Corral, Jason Moss, Tim S. Slugocki, Erinprit K. Singh, Melinda R. Davis, Suchitra Ravula, Jamie E. Spicer, Jenna L. Oelrich, Andrea Thornquist,