Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives
摘要:
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. Published by Elsevier Ltd.
Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives
摘要:
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. Published by Elsevier Ltd.
AITF (4-acetamidophenyl triflimide) mediated synthesis of amides, peptides and esters
作者:Eti Chetankumar、Swetha Bharamawadeyar、Chinthaginjala Srinivasulu、Vommina V. Sureshbabu
DOI:10.1039/d3ob01351k
日期:——
A simple, broadly applicable protocol for amidation and esterification reactions is described. Thereby, 4-acetamidophenyl triflimide (AITF), a crystalline stable reagent, is employed for the activation of carboxylic acids. The use of AITF as a coupling agent is demonstrated in the synthesis of peptides, amides and esters under mild conditions in good to excellent yields. Notably, peptide segment condensations
Rajanarendar; Mohan; Rao, E. Kalyan, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2008, vol. 47, # 5, p. 781 - 786
作者:Rajanarendar、Mohan、Rao, E. Kalyan、Reddy, A. Siva Rami、Praveen、Rao, M. Srinivasa
DOI:——
日期:——
Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives
作者: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、Chung-Mao Pan、Shelli R. McAlpine
DOI:10.1016/j.bmc.2010.07.042
日期:2010.9
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. Published by Elsevier Ltd.