2. Academic Validation
  3. New orally bioavailable 2-aminobenzamide-type histone deacetylase inhibitor possessing a (2-hydroxyethyl)(4-(thiophen-2-yl)benzyl)amino group

New orally bioavailable 2-aminobenzamide-type histone deacetylase inhibitor possessing a (2-hydroxyethyl)(4-(thiophen-2-yl)benzyl)amino group

  • Bioorg Med Chem. 2010 Jun 1;18(11):3925-33. doi: 10.1016/j.bmc.2010.04.033.
Shingo Kiyokawa 1,  Yoshiyuki Hirata,  Yasuo Nagaoka,  Makio Shibano,  Masahiko Taniguchi,  Masahide Yasuda,  Kimiye Baba,  Shinichi Uesato
Affiliations

Affiliation

  • 1 Department of Life Science and Biotechnology, Kansai University, Suita, Osaka 564-8680, Japan.
PMID: 20452226 DOI: 10.1016/j.bmc.2010.04.033
Abstract

New 2-aminobenzamide-type histone deacetylase (HDAC) inhibitors were synthesized. They feature a sulfur-containing bicyclic arylmethyl moiety-a surface recognition domain introduced to increase in cellular uptake-and a substituted tert-amino group which affects physicochemical properties such as aqueous solubility. Compound 22 with a (2-hydroxyethyl)(4-(thiophen-2-yl)benzyl)amino group reduced the volume of human colon Cancer HCT116 xenografts in nude mice to T/C 67% by oral administration at 45mg/kg, which was comparable to the rate (T/C 62%) for a positive control, MS-275. Western blot analyses as well as cell cycle and TUNEL assays by flow cytometry suggested that the two compounds inhibited the growth of Cancer cells via similar mechanisms.

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