Title of article :
Synthesis and biological activity of cyclotetrapeptide analogues of the natural HDAC inhibitor FR235222 Original Research Article
Author/Authors :
Stefania Terracciano، نويسنده , , Simone Di Micco، نويسنده , , Giuseppe Bifulco، نويسنده , , Paola Gallinari، نويسنده , , Raffaele Riccio، نويسنده , , Ines Bruno، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2010
Pages :
9
From page :
3252
To page :
3260
Abstract :
In the course of our ongoing efforts to discover new and more effective HDAC inhibitors useful for the development of promising anticancer candidates, we have recently undertaken a molecular modelling study on a small collection of FR235222 analogues, synthesized by us in the frame of a structure–activity relationship investigation, made in order to identify the key structural elements essential for the activity. Progress made in structure elucidation of HDAC active site, together with accurate docking calculations, provided new structural insights useful for a further refinement of the tetrapeptide scaffold which should assure an optimal interaction between the synthetic ligands and the biological target. Following the computer aided suggestions we synthesized six new cyclotetrapeptide analogues of the lead compound (3–8), bearing a carboxylic or an hydroxamic acid functionality as Zn binding moiety. Herein we describe their synthesis and their inhibition activity on different HDAC isoforms.
Journal title :
Bioorganic and Medicinal Chemistry
Serial Year :
2010
Journal title :
Bioorganic and Medicinal Chemistry
Record number :
1307328
Link To Document :
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