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http://dx.doi.org/10.5012/bkcs.2013.34.5.1487

Synthesis of Novel N-(2-Hydroxyphenyl)arylsulfonamides as Selective HDAC Inhibitory and Cytotoxic Agents  

Kim, Jungsu (Laboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University)
Chun, Pusoon (College of Pharmacy, Inje University)
Moon, Hyung Ryong (Laboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University)
Publication Information
Bulletin of the Korean Chemical Society / v.34, no.5, 2013 , pp. 1487-1493 More about this Journal
Abstract
Based on the finding that the 2-aminobenzamido group of MS-275 plays a crucial role in inhibiting HDACs through chelation of zinc existing at the active site of HDAC enzymes, novel N-(2-hydroxyphenyl)arylsulfonamide derivatives were synthesized for their potential ability to inhibit HDACs and evaluated for anticancer activity against human breast cancer cell line (MCF-7). Although the synthesized arylsulfonamides have failed to significantly inhibit total HDACs activity, phenyl carbamate-linked arylsulfonamide 10 and benzyl thiocarbamate-linked arylsulfonamide 15 exhibited good anticancer activities, which were only 4.3- and 3.6-fold lower anticancer activities, respectively, than MS-275 that is undergoing phase II clinical trials. These results suggest that these compounds may act as a selective HDAC inhibitor and probably N-(2-hydroxyphenyl) sulfamoyl group may play an important role in interacting with HDAC enzymes through chelation of zinc ion.
Keywords
HDAC inhibition; Anticancer activity; MS-275; N-(2-Hydroxyphenyl)sulfamoyl; Arylsulfonamide;
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