Ester-Functionalized Imidazolium- and Pyridinium-Based Ionic Liquids: Design, Synthesis and Cytotoxicity Evaluation

The QSAR model for the prediction of сytotoxicity of Ionic liquids (ILs) was developed using a data set of 1195 compounds. The Artificial Neural Networks learning technique was used. The predictive ability of the models was tested by means of cross-validation; the q2 value was 0.76 for the regression model. The prediction for the external evaluation set afforded high predictive power (q2 =0.75 for 239 compounds). The developed QSAR models evaluated the anticancer activity of a small set of virtual compounds and 6 compounds were selected for synthesis and biological testing. It was found that imidazolium and pyridinium ILs with C12 and C10 alkyl chain length exhibited significant cytotoxicity, particularly, compounds 3 and 6 were identified as the most potent anticancer agents with IC50 values 0.18 µM and 5.75 µM against Hep-2 cell line and different acute toxicity levels to cladoceran Daphnia magna. Molecular docking showed that the high cytotoxic activity of imidazolium and pyridinium ILs with C12 alkyl chain length may be associated with specific DNA binding in the region of CG nucleotides.