Anticancer activity features of imidazole-based ionic liquids and lysosomotropic detergents: in silico and in vitro studies

Long-chain imidazole-based ionic liquids (compounds 2, 4, 9) and lysosomotropic detergents (compounds 7, 3, 8) with potent anticancer activity were synthesized. Their inhibitory activities against neuroblastoma and leukaemia cell lines were predicted by the new in silico QSAR models. The cytotoxic activities of the synthesized imidazole derivatives were investigated on the SK-N-DZ (human neuroblastoma) and K-562 (human chronic myeloid leukaemia) cell lines. Compounds 2 and 7 showed the highest in vitro cytotoxic effect on both cancer cell lines. The docking procedure of compounds 2 and 7 into the NAD + coenzyme binding site of deacetylase sirtuin 1 (SIRT1) showed the formation of protein-ligand complexes with a calculated binding energy of -8.0 and − 8.1 kcal/mol, respectively. The interaction of SIRT1 with compounds 2, 7 and 9 and the interaction of bromodomain-containing protein 4 (BRD4) with compounds 7 and 9 were also demonstrated by thermal shift assay. Compounds 2, 4, 7, and 9 inhibited SIRT1 deacetylase activity in the SIRT-Glo assay. Compounds 7 and 9 showed a moderate inhibitory activity against aurora kinase A. In addition, compounds 3, 4, 8, and 9 inhibited the janus kinase 2 activity. The results obtained showed that long-chain imidazole derivatives exhibited cytotoxic activities on K562 leukaemia and SK-N-DZ neuroblastoma cell lines. Furthermore, these compounds inhibited a panel of molecular targets involved in leukaemia and neuroblastoma tumorigenesis. All these results suggest that both long-chain imidazole-based ionic liquids and lysosomotropic detergents may be an effective alternative for the treatment of neuroblastoma and chronic myeloid leukemia and merit further investigation.