Investigation of the combinatorial anticancer effects of imidazolium-based ionic liquids and lysosomotropic detergents with cisplatin and doxorubicin

In the context of rapidly developing resistance caused by mutations in genes that control oncogenic pathways and cancer cell survival, as well as to known and widely accessible antitumor drugs, combined strategies are critical as a modern approach to cancer therapy. The in vitro results from a study of several long-chain N-alkylimidazole derivatives, combined with the known anticancer drugs doxorubicin and cisplatin, using cell lines of chronic myeloid leukemia K562, neuroblastoma SK-N-DZ, and mammary gland adenocarcinoma MCF7, show that the imidazolium-based ionic liquids 1-dodecyl-3-methylimidazolium chloride (IMC₁₂C₁-Cl), 1-dodecyloxycarbonylmethyl-3-methylimidazolium chloride (IMC₁CH₂COOC₁₂-Cl), and, to a lesser extent, lysosomotropic detergent 1-dodecylimidazole (IMC₁₂) consistently stand out as the most promising across all cell lines. IMC₁₂C₁-Cl demonstrated significant reductions in cisplatin and doxorubicin doses, along with enhanced cytotoxic effects, in both K562 and SK-N-DZ cells, with DRI values of 4.36 μM for cisplatin and 15.00 μM for doxorubicin. IMC₁CH₂COOC₁₂-Cl showed high DRI and synergism in MCF7 cells and moderate activity in SK-N-DZ cells. IMC₁₂C₁-Cl and IMC₁CH₂COOC₁₂-Cl appear to be promising candidates for the development and evaluation of their combinatorial anticancer effects.