Synthesis, enzymatic inhibition, and cancer cell growth inhibition of novel delta-lactam-based histone deacetylase (HDAC) inhibitors

  • Bioorg Med Chem Lett. 2006 Aug 1;16(15):4068-70. doi: 10.1016/j.bmcl.2006.04.091.
Hwan Mook Kim  1 ,  Kiho Lee ,  Bum Woo Park ,  Dong Kyu Ryu ,  Kangjeon Kim ,  Chang Woo Lee ,  Song-Kyu Park ,  Jung Whan Han ,  Hee Yoon Lee ,  Hyun Yong Lee ,  Gyoonhee Han
Affiliations
  • 1. Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-333, Republic of Korea.
PMID: 16723227 DOI: 10.1016/j.bmcl.2006.04.091
Abstract

delta-Lactam-based hydroxamic acids, inhibitors of histone deacetylase (HDAC), have been synthesized via ring closure metathesis of key diene intermediates followed by conversion to hydroxamic acid analogues. The hydroxamic acids 12a, 12b, and 17c showed potent inhibitory activity in HDAC enzyme assay. The hydroxamic acid 12b exhibited growth inhibitory activity on five human tumor cell lines, showing good sensitivity on the MDA-MB-231 breast tumor cell.