Synthesis and Preliminary Antiproliferative Activity of Novel 4-Substituted Phenylsulfonyl Piperazines with Tetrazole Moiety

A series of 1-substituted-1H-tetrazole-5-thiol building blocks were synthesized (6a-h) and coupled by S-alkylation with 2-bromo-1-(4-(substituted phenylsulfonyl)piperazin-1-yl)ethanone (4a-c) using triethylamine in ethanol under reflux conditions. The structures of newly synthesized compounds were characterised by nuclear magnetic resonance and mass spectral data. Further, the hybrid compounds (7a-x) were screened for in vitro inhibitory effect on human cervical carcinoma (SiHA), breast adenocarcinoma (MDA-MB-235) and human pancreatic carcinoma (PANC-1) cell lines using sulforhodamine B assay. Antiproliferative assay revealed that most of the target compounds exhibited significant growth inhibitory activity (GI(50)<= 0.1 mu M) against all tested cancer cell lines compared to the reference drug. The most promising active compounds in this series were 7e and 7n, which displayed antiproliferative activity with GI(50)<= 0.2 mu M against the SiHa and MIDA-MB-231 cancer cell lines, whereas compounds 7g, 7l, 7p, 7s and 7t exhibited antiproliferative activity with GI(50)<= 0.1 mu M against the PANC-1 cell line. Thus the tetrazole-piperazinesulfonamide hybrid compounds could be potential leads for the development of new antiproliferative agents.