Biophysical insight into the binding mechanism of 1,3-benzodioxole-based lidocaine tagged ionic liquids with BSA: An in-silico, and spectroscopic studies

Abstract

The interaction between bio-macromolecules and drugs has attracted significant interest for several decades due to their pharmacokinetics and pharmacological implications. Ionic liquids have a major importance in the development of effective drugs that can majorly target and bind to the proteins present in the body. A slight disturbance in the micro-environment of protein induced by a drug can alter the conformations of proteins to lead them to work differently. The interaction of ionic liquids with proteins present in blood such as HSA (Human Serum Albumin) and BSA (Bovine Serum Albumin) provides useful evidence for synthesizing API-based liquid drug and their delivery. In this study, the interaction of BSA with LPAc & LPOT ILs (LPAc: N-(benzo[d][1,3]dioxol-5-ylmethyl)-2-((2,6-dimethylphenyl)amino)-N,N-diethyl-2-oxoethan-1-aminium acetate and LPOT: N-(benzo[d][1,3]dioxol-5-ylmethyl)-2-((2,6-dimethylphenyl)amino)-N,N-diethyl-2-oxoethan-1-aminiumtrifluoromethane sulfonate) using spectroscopic methods like UV–visible, fluorescence, CD spectroscopy, computational studies (molecular docking, MD simulation studies, and ADMET studies). UV–vis spectra showed a slight rise in absorbance intensity with the addition of ionic liquid. A static quenching of BSA with blue shift was observed according to fluorescence spectra on the addition of ionic liquids (LPAc & LPOT) and conformational alterations of BSA were observed by analyzing CD spectra. LPAc and LPOT showed strong binding with BSA with molecular docking scores of −330.2 and −365.2 kcal/mol respectively. The molecular dynamic simulation and in-silico pharmacological and pharmacokinetics studies support the spectroscopic study and molecular docking results inferring that LPOT ionic liquid showed strong binding interactions with BSA. In-vitro studies against A549 cell lines showed that both LAPc and LPOT ionic liquids had antiproliferative properties and LPOT has better anticancer activity as inferred by IC50 value: 38.83 and may be further useful for drug design as cancer therapeutic.