1609172-25-9Relevant articles and documents
Azaindolylsulfonamides, with a more selective inhibitory effect on histone deacetylase 6 activity, exhibit antitumor activity in colorectal cancer HCT116 cells
Lee, Hsueh-Yun,Tsai, An-Chi,Chen, Mei-Chuan,Shen, Po-Jung,Cheng, Yun-Ching,Kuo, Ching-Chuan,Pan, Shiow-Lin,Liu, Yi-Min,Liu, Jin-Fen,Yeh, Teng-Kuang,Wang, Jing-Chi,Chang, Chi-Yen,Chang, Jang-Yang,Liou, Jing-Ping
, p. 4009 - 4022 (2014/06/09)
A series of indolylsulfonylcinnamic hydroxamates has been synthesized. Compound 12, (E)-3-(3-((1H-pyrrolo[2,3-b]pyridin-1-yl)sulfonyl)phenyl)-N- hydroxyacrylamide, which has a 7-azaindole core cap, was shown to have antiproliferative activity against KB, H460, PC3, HSC-3, HONE-1, A549, MCF-7, TSGH, MKN45, HT29, and HCT116 human cancer cell lines. Pharmacological studies indicated that 12 functions as a potent HDAC inhibitor with an IC50 value of 0.1 μM. It is highly selective for histone deacetylase 6 (HDAC6) and is 60-fold more active than against HDAC1 and 223-fold more active than against HDAC2. It has a good pharmacokinetic profile with oral bioavailability of 33%. In in vivo efficacy evaluations in colorectal HCT116 xenografts, compound 12 suppresses tumor growth more effectively than SAHA (1, N-hydroxy-N′- phenyloctanediamide) and is therefore seen as a suitable candidate for further investigation.
