Binding Study of Antibacterial Drug Ciprofloxacin with Imidazolium-Based Ionic Liquids Having Different Halide Anions: A Spectroscopic and Density Functional Theory Analysis.

Herein, we have shown the interaction of an antibiotic drug ciprofloxacin (CIP) with three surface-active ionic liquids (ILs), having the same cation and different anions, namely, 1-decyl-3-methylimidazoliumtetrafluoroborate [C10mim][BF4], 1-decyl-3-methylimidazolium bromide [C10mim][Br], and 1-decyl-3-methylimidazolium chloride [C10mim][Cl]. This study has been performed by exploiting various spectroscopic techniques such as steady-state fluorescence, time-resolved fluorescence, and UV-visible spectroscopy. The fluorescence emission study of CIP with ILs was performed at various concentrations of all the three ILs. The emission spectra of CIP decreased in the presence of ILs, suggesting complex formation between CIP-IL. The effect of different concentrations of ILs on the emission spectra of CIP was exploited in terms of quenching and binding parameters. Further, fluorescence emission study was validated by the time-resolved fluorescence technique by measuring the average lifetime (τavg) of CIP in the presence of all the three ILs. The τavg value of the drug changed with the addition of ILs, which suggests complex formation between the drug and ILs. This complex formation was also confirmed by UV-visible spectroscopy results of CIP with all the three ILs. Further, for evaluating the thermodynamic parameters of the CIP-IL interactions, isothermal titration calorimetry (ITC) was performed. The ITC experiment yielded the thermodynamic parameters, ΔH (change in the enthalpy of association), ΔG (Gibbs free energy change), ΔS (entropy change), and binding constant (Ka). The binding parameters driven by ITC revealed that CIP-IL interactions are spontaneous in nature and enthalpy-driven, involving hydrophobic forces. Further, the classical density functional theory (DFT) calculations were performed, which provided deep insight for CIP-IL complex formation.

A biophysical approach to study the impact of muscle relaxant drug tizanidine on stability and activity of serum albumins.

The binding affinity of a drug with carrier proteins plays a major role in the distribution and administration of the drug within the body. Tizanidine (TND) is a muscle relaxant having antispasmodic and antispastic effects. Herein, we have studied the effect of tizanidine on serum albumins by spectroscopic techniques, such as absorption spectroscopic analysis, steady, state fluorescence, synchronous fluorescence, circular dichroism, and molecular docking. The binding constant and number of binding sites of TND with serum proteins were determined by means of fluorescence data. The thermodynamic parameters, like Gibbs' free energy (ΔG), enthalpy change (ΔH), and entropy change (ΔS), revealed that the complex formation is spontaneous, exothermic, and entropy driven. Further, synchronous spectroscopy revealed the involvement of Trp (amino acid) responsible for quenching of intensity in fluorescence in serum albumins in presence of TND. Circular dichroism results suggest that more folded secondary structure of proteins. In BSA the presence of 20 µM concentration of TND was able to gain most of its helical content. Similarly, in HSA the presence of 40 µM concentration of TND has been able to gain more helical content. Molecular docking and molecular dynamic simulation further confirm the binding of TND with serum albumins, thus validating our experimental results.

Synthesis of Novel Benzimidazolium Gemini Surfactants and Evaluation of Their Anti-Candida Activity.

Owing to the rise in antimicrobial and chemotherapeutic drug resistance, there is a desperate need to formulate newer as well as more effective agents. With this perspective, here we outline the synthesis of two novel gemini surfactants with different substitutions at the nitrogen atom of the benzimidazolium ring. Both the compounds induced significant reductions in Candida growth in various yeast strains. The reduction in Candida growth seemed likely through the reduction in ergosterol biosynthesis: a sterol constituent of yeast cell membranes. Different concentrations of both compounds were used to determine the cellular ergosterol content which indicates an important disordering of the ergosterol biosynthetic pathway. Cytotoxic studies were carried out using HEK 293 (human embryonic-kidney cells) and Galleria mellonella larvae (an in vivo model of antimicrobial studies). Administration of both the compounds to G. mellonella larvae diseased by the yeast Candida albicans resulted in increased survival indicating their in vivo activity.