Noncovalent Conjugates of Ionic Liquid with Antibacterial Peptide Melittin: An Efficient Combination against Bacterial Cells

[Image: see text] Growing antibiotic resistance has become a major health problem and has encouraged many researchers to find an alternative class of antibiotics. Combination therapy (covalent/noncovalent) is supposed to increase antibacterial activity leading to a decrease in administration dosage, thus lowering the risk of adverse side effects. The covalent coupling sometimes leads to instability and loss in the structure of AMPs. Therefore, herein, we have reported innovative research involving the noncovalent coupling of melittin (MEL), an antimicrobial peptide with a series of synthesized less toxic pyrrolidinium-based ionic liquids (ILs) for which MTT assay was performed. The antibacterial results of conjugates showed remarkable improvement in the MIC value as compared to MEL and ILs alone against Escherichia coli and Staphylococcus aureus. In addition, hemocompatibility results suggested good selectivity of the noncovalent conjugate as a potential antibiotic agent. Further, the docking study was employed to acquire the most favorable conformation of MEL in the presence of ILs. The best possible complex was further studied using various spectroscopic techniques, which showed appreciable binding and stability of the complex.