Appraisal of 1-Butylimidazole-Derived Ionic Liquids as Anthelmintic Agents: An Experimental and In Silico Approach

We have synthesized and characterized 1-butyl-3-alkylimidazolium derived ionic liquids (ILs) functionalized with various alkyl groups (-C2H5, -C4H9, -C6H13, -C8H17, and -C10H21) and counter anions ((Formula presented.)). Further, these ILs were tested for the vermicidal activity and cell-viability study against the Pheretima posthuma (Indian earthworm) and MC3T3-L1 cells, respectively. IL-OH with higher alkyl chains (-C10H21) displayed promising vermicidal activity as compared to other counterparts (IL−Br and IL-BF4). Further, quantitative-structure-activity-relationships (QSAR) modelling was carried out using density functional theory (DFT) derived quantum mechanical descriptors to assess the factors responsible for the biological activities. Based on the QSAR study it was found that LUMO of the anion and polar surface area of the cation possess significant correlation (r2, 0.85; RMSE, 0.06). Also, receptor-binding based molecular docking was carried out to study the binding patterns of the tested IL. Introduction. In past few decades, ionic liquids (ILs) have generated paramount interest in several field of chemistry, i.e., catalysis, electrochemistry,, biotechnology, biomass energy and pharmaceutical applications–, and many others. This wide range of applications are due to their characteristic tunable nature of ILs which facilitate desired biochemical properties via varying their counter anions and alkyl chain length., Subsequent tailoring of biologically active cations or anions can add substantial potential to their therapeutic implication and administration as active pharmaceutical ingredients (APIs)., Efforts are made to probe the effects of various anions, alkyl chains and charge on the quaternary nitrogen atom. It has been articulated that medicinal aspect of ILs is greatly impeded by their toxicity; however, attempts are in the progress to afford a balance between toxicity and biochemical/ biopharmaceutical properties. In particular, the maxim “poison is in the dose”, encouraged to develop ILs as useful therapeutics. Earlier, we have screened the imidazolium derived ILs for their vermicidal activity with varying alkyl chains (R= -C2H5, -C4H9, -C6H13, -C8H17) and Br−/OH− as counter anions.