Design, synthesis and preliminary activity assay of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as novel Histone deacetylases (HDACs) inhibitors

Histone deacetylases (HDACs) are enzymes involved in tumor genesis and development. Herein, we report a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDACs inhibitors. The preliminary biological screening showed that most of our compounds exhibited potent inhibitory activity against HDACs. Within this series, five compounds, 13a (IC50 = 0.58 +/- 0.10 mu M), 7d (IC50 = 1.00 +/- 0.16 mu M), 81 (IC50 = 1.06 +/- 0.14 mu M), 7i (IC50 = 1.17 +/- 0.19 mu M) and 7a (IC50 = 1.29 +/- 0.15 mu M) possessed better HDACs inhibitory activity than Vorinostat (IC50 = 1.48 +/- 0.20 mu M). So these five compounds could be used as novel lead compounds for further design of HDACs inhibitors. The anti-proliferative activities of a few compounds and the structure-activity relationships are also briefly discussed. (C) 2010 Elsevier Ltd. All rights reserved.