Structure-activity relationship studies of a series of novel delta-lactam-based histone deacetylase inhibitors

  • J Med Chem. 2007 May 31;50(11):2737-41. doi: 10.1021/jm0613828.
Hwan Mook Kim  1 ,  Dong-Kyu Ryu ,  Yongseok Choi ,  Bum Woo Park ,  Kiho Lee ,  Sang Bae Han ,  Chang-Woo Lee ,  Moo-Rim Kang ,  Jong Soon Kang ,  Shanthaveerappa K Boovanahalli ,  Song-Kyu Park ,  Jung Whan Han ,  Tae-Gyu Chun ,  Hee-Yoon Lee ,  Ky-Youb Nam ,  Eun Hyun Choi ,  Gyoonhee Han
Affiliations
  • 1. Bioevaluation Center, KRIBB, Daejeon 305-806, Korea.
Abstract

We synthesized a series of delta-lactam-based HDAC inhibitors that were identified with various degrees of anti-inflammatory and cell growth inhibitory activities. Compounds possessing significant HDAC inhibitory activity exhibited both anti-inflammatory and cell growth inhibitory activities as well as significant tumor growth inhibition in the in vivo tumor xenograft experiments. Besides, these compounds demonstrated anti-inflammatory properties in vitro via suppression of the production of the proinflammatory cytokine TNF-alpha and nitric oxide by LPS-stimulated RAW264.7 cells.