Design, synthesis and biological evaluation of urea-based benzamides derivatives as HDAC inhibitors
- 274 Downloads
A new class of urea-based benzamides derivatives were designed and synthesized as histone deacetylases inhibitors. Biological evaluations of these compounds included the inhibitory activity of histone deacetylases1 and cytotoxicity against different cancer cell lines in vitro. Most compounds exhibited potential histone deacetylases inhibitory activity and antitumor activities. Compound 5h behaved as potent histone deacetylases1 inhibitor (IC50 = 0.182 μM) and showed comparable cytotoxicity with MS-275, which could be considered as a potential candidate compound for further development.
KeywordsBenzamides derivatives HDAC inhibitors Design Synthesis
This study was supported by the National Natural Science Foundation of China (Grant No. 81202410), Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120096120010) and Fundamental Research Funds for the Central Universities (Grant No. JKPZ2013003).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- Dallavalle S, Cincinelli R, Nannei R, Merlini L, Morini G, Penco S, Pisano C, Vesci L, Barbarino M, Zuco V, De Cesare M, Zunino F (2009) Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. Eur J Med Chem 44:1900–1912. doi: 10.1016/j.ejmech.2008.11.005 CrossRefPubMedGoogle Scholar
- Hu E, Dul E, Sung CM, Chen Z, Kirkpatrick R, Zhang GF, Johanson K, Liu R, Lago A, Hofmann G, Macarron R, De Los Frailes M, Perez P, Krawiec J, Winkler J, Jaye M (2003) Identification of novel isoform-selective inhibitors within class I histone deacetylases. J Pharmacol Exp Ther 307:720–728. doi: 10.1124/jpet.103.055541 CrossRefPubMedGoogle Scholar
- Khan N, Jeffers M, Kumar S, Hackett C, Boldog F, Khramtsov N, Qian X, Mills E, Bergh SC, Carey N, Finn PW, Collins LS, Tumber A, Ritchie JW, Jensen PB, Lichenstein HS, Sehested M (2008) Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem J 409:581–589. doi: 10.1042/bj20070779 CrossRefPubMedGoogle Scholar
- Sakkiah S, Meganathan C, Sohn YS, Namadevan S, Lee KW (2012) Identification of important chemical features of 11beta-hydroxysteroid dehydrogenase type1 inhibitors: application of ligand based virtual screening and density functional theory. Int J Mol Sci 13:5138–5162. doi: 10.3390/ijms13045138 CrossRefPubMedPubMedCentralGoogle Scholar