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http://dx.doi.org/10.5012/bkcs.2011.32.6.1891

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

Chun, Pu-Soon (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Kim, Won-Hee (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Kim, Jung-Su (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Kang, Jin-Ah (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Lee, Hye-Jin (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Park, Ji-Young (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Ahn, Mee-Young (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Kim, Hyung-Sik (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Moon, Hyung-Ryong (College of Pharmacy and Research Institute for Drug Development, Pusan National University)
Publication Information
Bulletin of the Korean Chemical Society / v.32, no.6, 2011 , pp. 1891-1896 More about this Journal
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.
Keywords
HDAC inhibition; Anticancer activity; SAHA; Bulky cap;
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