Design, synthesis and biological evaluation of novel aliphatic amido/sulfonamido-quaternary ammonium salts as antitumor agents

Abstract

RhoB, one of the upstream signaling proteins of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway, is frequently mutated in human cancer. Based on a piperazine alkyl derivative that induced apoptosis via up-regulation of RhoB, we synthesized novel aliphatic amido/sulfonamido-quaternary ammonium salts and evaluated their biological activities using an in vitro growth inhibition assay and RhoB promoter assay in human cancer cells. Compound 3a was the most promising anticancer agent in the series, based upon its potent growth inhibition via RhoB-mediated signaling. These novel aliphatic amido/sulfonamido- quaternary ammonium salts may be useful as a platform for development of anticancer chemotherapeutic agents. (C) 2012 Elsevier Ltd. All rights reserved.