Design, Synthesis and Anti-tumor Activity Evaluation of a Novel Series of Isoxazoles Bearing (1-Bi(4-fluorophenyl)methyl)piperazine Unit

Twelve novel isoxazoles containing (1-bi(4-fluorophenyl) methyl) piperazine unit were prepared in two steps starting from propargyl bromide, (1-bi(4-fluorophenyl) methyl) piperazine and hydroxymoyl chlorides with moderate yield (21%similar to 76%). The structures of the new compounds were characterized by IR, MS, H-1 NMR, C-13 NMR and elemental analysis, and their in vitro anti-tumor activity was screened. The bioactive assay for the newly prepared compounds manifested that ten newly isoxazole derivatives exhibited good to excellent inhibitory activity against CDC25B in 20 mu g/mL with inhibition of 64.15% similar to 95.87% and IC50 of 35.62 similar to 13.67 mu g/mL. Four isoxazoles exhibited good to excellent inhibitory activity against Leukemia cell HL-60 in 40 mu mol/L (IC50: 36.51 similar to 15.25 mu g/mL), 2-(2-fluorophenyl)-5-(1-(bi-(4-fluorophenyl) methyl)piperazine) methylisoxazole (5g) and 2-(4-fluorophenyl)-5-(1-(bi-(4-fluorophenyl) methyl) piperazine) methylisoxazole (5h) exhibited good to excellent inhibitory activity against Lung cancer cell A-549 (IC50 value up to 21.09 and 35.36 mu g/mL, respectively).