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Synthesis and Importance of Bulky Aromatic Cap of Novel SAHA Analogs for HDAC Inhibition and Anticancer Activity

Authors :
Mee-Young Ahn
Pusoon Chun
Hyung Sik Kim
Hye Jin Lee
Jiyoung Park
Jungsu Kim
Won Hee Kim
Jin-Ah Kang
Hyung-Ryong Moon
Source :
Bulletin of the Korean Chemical Society. 32:1891-1896
Publication Year :
2011
Publisher :
Korean Chemical Society, 2011.

Abstract

On the basis of potent HDAC-inhibitory activity and anticancer activity of SAHA, novel SAHA derivatives 3a-d and 7 with a bulky cap such as p-dimethylaminophenyl, 4-phenylaminophenyl, 4-phenyloxyphenyl, 9H-fluorenyl or naphthalenyl ring were synthesized starting from the corresponding aryl amines or naphthalenyl acetic acid using an EDC-mediated amide coupling reaction in the presence of HOBt followed by a nucleophilic addition-elimination reaction with hydroxylamine. Compounds 3b, 3c and 3d showed more potent inhibitory activity on total HDACs (14~27-fold), HDAC1 (8~15-fold), HDAC2 (1.3~25-fold) and HDAC7 (1~3-fold) and more potent anticancer activity (2~22-fold) against MCF-7, MDA-MB-231, MCF-7/Dox, MCF-7/Tam, SK-OV-3, LNCaP and PC3 human cancer cell lines than SAHA.

Details

ISSN :
02532964
Volume :
32
Database :
OpenAIRE
Journal :
Bulletin of the Korean Chemical Society
Accession number :
edsair.doi...........8c1c912c6ab1b8fc5f7bf87a93bacc9f
Full Text :
https://doi.org/10.5012/bkcs.2011.32.6.1891