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Indexed by:期刊论文

Date of Publication:2012-06-01

Journal:EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Included Journals:SCIE、PubMed、Scopus

Volume:52

Page Number:111-122

ISSN No.:0223-5234

Key Words:Histone deacetylase; Histone deacetylase inhibitor; Docking; Molecular dynamics

Abstract:Histone deacetylases inhibitors (HDACIs) have become an attractive class of anticancer agents. In order to find some novel potent HDACIs, we designed and synthesized a series of L-2-benzyloxycarbonylamino-8-(2-pyridyl)-disulfidyloctanoic acid derivatives. All compounds exhibited potent HDAC-inhibitory activity, and two of them had similar potency to TSA. The introduction of 2-amino-4-phenylthiazole or 9-methyleneoxy-fluorenyl group at the surface recognize domain of these HDACIs could greatly increase their HDAC-inhibitory activity. Molecular modeling studies indicated that coordination of the zinc ion by these inhibitors, and formation of hydrogen bond and hydrophobic interaction between inhibitors and HDACs were essential for the HDAC-inhibitory activities of these inhibitors. Asp181, Asp269, Leu276 and Tyr308 in the active site of HDAC2 gave favorable contributions for binding with all compounds. (C) 2012 Elsevier Masson SAS. All rights reserved.