A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles has been identified as a new class of histone deacetylase inhibitors. Compounds 8, 11, 12, 13, and 14 demonstrated stronger antiproliferative activities than 1 (SAHA) with GI(50) values ranging from 0.36 to 1.21 mu M against Hep3B, MDA-MB-231, PC-3, and A549 human cancer cell lines. Lead compound 8 showed remarkable HDAC 1, 2, and 6 isoenzymes inhibitory activities with IC50 values of 12.3, 4.0, 1.0 nM, respectively, which are comparable to I. In in vivo efficacy evaluation against lung A549 xenograft model, 8 displayed better antitumor activity than compound 1.
Date:
2012-04
Relation:
Journal of Medicinal Chemistry. 2012 Apr;55(8):3777-3791.
