Design and synthesis of N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential antitumor agents

A series of novel N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential telomerase inhibitors were synthesized. The bioassay tests show that compound 4a exhibited high activity against human gastric cancer cell SGC-7901, liver cancer Hep-G2 and human prostate PC-3 cell lines with IC50 values of 21.23 +/- 0.99, 29.43 +/- 0.32 and 30.89 +/- 1.07 mu M, respectively. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results show that compound 4a can inhibit telomerase with IC50 value of 4.0 +/- 0.32 mu M. Docking simulation was performed to position compound 4a into the telomerase (3DU6) active site to determine the probable binding model. (C) 2011 Elsevier Ltd. All rights reserved.