Synthesis and biological evaluation of novel aliphatic amido-quaternary ammonium salts for anticancer chemotherapy: Part I

We synthesized novel aliphatic amido-quaternary ammonium salts in an effort to discover anticancer agents that increase Ras homolog gene family, member B, (RhoB) levels. These compounds exert anti-proliferative activities against several human cancer cell types. Seventeen compounds, varying in aliphatic carbon chain length and N-substituents, were synthesized and their biological activities were evaluated. Of these 17 compounds, compound 3i emerged as the most promising anticancer compound by promoting apoptosis through the RhoB mediated pathway. Potent biological activities observed for these novel aliphatic amido-quaternary ammonium salt analogues support their potential as anticancer, chemotherapeutic agents. A series of aliphatic amido-quaternary ammonium salts were designated, synthesized and evaluated for anticancer chemotherapy. Compound 3i was emerged as the most promising anticancer compound promoting apoptosis through RhoB mediated pathway. [Display omitted] ►17 Novel aliphatic amido-quaternary ammonium salts were synthesized and evaluated.► 3c, 3f, and 3i showed better in vitro activity than the lead compound.► 3i emerged as the most promising agent through RhoB mediated pathway.►Anti-proliferative activity is significantly related to the RhoB activation.►These compounds could be promising anticancer agents for anticancer chemotherapy.