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 μM 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 IC 50 values of 12.3, 4.0, 1.0 nM, respectively, which are comparable to 1. In in vivo efficacy evaluation against lung A549 xenograft model, 8 displayed better antitumor activity than compound 1.
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
Lai, M. J., Huang, H. L., Pan, S. L., Liu, Y. M., Peng, C. Y., Lee, H. Y., Yeh, T. K., Huang, P. H., Teng, C. M., Chen, C. S., Chuang, H. Y., & Liou, J. P. (2012). Synthesis and biological evaluation of 1-arylsulfonyl-5-(N -hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo. Journal of Medicinal Chemistry, 55(8), 3777-3791. https://doi.org/10.1021/jm300197a