Discovery of adamantane based highly potent HDAC inhibitors

  • Bioorg Med Chem Lett. 2013 May 1;23(9):2532-7. doi: 10.1016/j.bmcl.2013.03.002.
Balasubramanian Gopalan  1 ,  Thanasekaran Ponpandian ,  Virendra Kachhadia ,  Kuppusamy Bharathimohan ,  Radhakrishnan Vignesh ,  Velaiah Sivasudar ,  Shridhar Narayanan ,  Bhonde Mandar ,  Rajendran Praveen ,  Nithyanandan Saranya ,  Sriram Rajagopal ,  Sridharan Rajagopal
Affiliations
  • 1. Drug Discovery Research Centre, Orchid Chemicals & Pharmaceuticals Ltd, Chennai 600119, India.
PMID: 23538115 DOI: 10.1016/j.bmcl.2013.03.002
Abstract

Herein, we report the development of highly potent HDAC inhibitors for the treatment of Cancer. A series of adamantane and nor-adamantane based HDAC inhibitors were designed, synthesized and screened for the inhibitory activity of HDAC. A number of compounds exhibited GI50 of 10-100 nM in human HCT116, NCI-H460 and U251 Cancer cells, in vitro. Compound 32 displays efficacy in human tumour animal xenograft model.