Safe and selective anticancer agents from tetrafluorinated azobenzene-imidazolium ionic liquids: Synthesis, characterization, and cytotoxic effects.

Abstract

A new series of tetrafluorinated azobenzene-imidazolium salts is reported. The azobenzene and imidazolium moieties were functionalized with long alkyl chains and connected via a methylene spacer of varying lengths (n = 3-12). They were characterized using FTIR and NMR spectroscopy, and elemental microanalysis. The cytotoxic potential of these ionic dimers against neuroblastoma (SHSY-5Y), estrogen-positive breast cancer cells (MCF-7), triple-negative breast cancer cells (MDA-MB-231), cervical cancer cells (HeLa), and human skin fibroblasts (Hs27) was evaluated using the MTT assay. The cytotoxicity of these ionic liquids (ILs) was dependent on the spacer length. A cut-off effect was observed, wherein the cytotoxicity of the ILs was enhanced by increasing the nonpolar, hydrophobic spacer length up to a threshold and the potency was leveled off upon chain elongation. All ILs exhibited selective and remarkable inhibition potentials against HeLa cells in a dose-dependent manner, which was 2-22 times stronger than that of etoposide, a clinical anticancer drug. These ILs were less toxic toward skin fibroblasts as implied by much higher IC50 values. The long-spacer ILs (n = 7-10) were very selective toward HeLa cells. They had a broad safety window with selectivity indices ranging between 5.6 and 11.0. The selectivity of these compounds toward HeLa cells may serve as a new strategy for the design and development of safe and effective chemotherapeutics.