Novel imidazole-based hydrazonoyl cyanides and amidrazones containing N(N,O)-heterocycles: selective synthesis, reaction mechanisms and preliminary anticancer evaluation

Abstract

Two series of novel hybrid heterocyclic compounds that combine the imidazole ring with bioactive piperidine, morpholine or piperazine heterosystems, through a hydrazone unit, were easily obtained by two competitive pathways. Starting from 5-amino-4-cyanoformimidoyl imidazoles and 1-aminopiperidine, 4-aminomorpholine or 1-amino-4-methylpiperazine under mild acidic media led to the selective synthesis of 5-aminoimidazole 4-carboxamidrazones, whereas the corresponding 4-hydrazonoyl cyanide derivatives were obtained under stronger acidic conditions. These highly functionalized imidazoles provide convenient synthetic precursors to a vast array of heterocycles with potential pharmaceutical applications. The reaction mechanisms were elucidated on the basis of experimental assays and in silico calculations. The compounds were screened against colorectal cancer HCT116-p53 wt cell line, and significant IC50 values of 3.69 µM and 4.83 µM were obtained.