Unveiling the interaction, cytotoxicity and antibacterial potential of pyridine derivatives: an experimental and theoretical approach with bovine serum albumin.

The binding interactions between bovine serum albumin (BSA) and three pyridine derivatives, i.e., 2-(5-bromopyridin-3-yl) acetic acid (L1), 3-bromo-5-nitropyridine (L2) and 2-chloro-4-nitropyridine (L3), have been carried out using UV-Vis and fluorescence spectroscopic methods. Fluorescence intensity quenching is observed by adding L2 and L3 to the BSA solution. The quenched fluorescence emission is due to the static nature. An isothermal titration calorimetry (ITC) experiment shows the binding ability of L1 with BSA. The binding constants are found to be 7.23 ± 0.32 × 105 M-1 for L1. The thermodynamic parameters were calculated from ITC measurements (i.e., ∆H = -2.78 ± 0.08 kcal/mol, ∆G = -5.65 ± 0.25 kcal/mol, and -T∆S = -2.87 ± 0.11 kcal/mol), which indicated that the protein-ligand complex formation between L1 and BSA is mainly due to the hydrogen bonds and van der Waals interactions. Cyclic voltammetry (CV) and structure activity and relationship (SAR) studies have been carried out to establish the relationship between ligands and proteins. Additionally, we conducted an antibacterial assay with gram-positive Staphylococcus aureus, Enterococcus faecalis, and negative bacterial strains Acinetobacter baumannii and Escherichia coli against L1, L2, and L3, aiming to address the challenges posed by the co-existence of multidrug-resistant bacteria. Finally, drosophila is used to test the cytotoxicity of ligands L1, L2, and L3's in vitro.

Antibacterial and cytotoxicity studies of pyrrolo-based organic scaffolds and their binding interaction with bovine serum albumin.

Two pyrrolo-based compounds, 1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid (L1) and 1H-pyrrolo[3,2-c]pyridine-4-carboxylic acid (L2), were employed for the detection of bovine serum albumin (BSA) by UV-Vis and fluorescence spectroscopic methods in phosphate buffer solution (pH = 7). In the presence of L1 and L2, the fluorescence emission of BSA at 340 nm was quenched and concomitantly a red-shifted emission band appeared at 420 nm (L1)/450 nm (L2). The fluorescence spectral changes indicate the protein-ligand complex formation between BSA and L1/L2. An isothermal titration calorimetry (ITC) experiment was conducted to determine the binding ability between BSA and L1/L2. The binding constants are found to be 4.45 ± 0.22 × 104 M-1 for L1 and 2.29 ± 0.11 × 104 M-1 for L2, respectively. The thermodynamic parameters were calculated from ITC measurements (i.e. ∆rH = -40 ± 2 kcal/mol, ∆rG = -4.57 ± 0.22 kcal/mol and -T∆rS = 35.4 ± 1.77 kcal/mol), which indicated that the protein-ligand complex formation between L1/L2 with BSA is mainly due to the electrostatic interactions. The protein-ligand interactions were studied by performing molecular docking. Further, the antibacterial assay of L1 and L2 was conducted against gram-positive and gram-negative bacterial strains in an effort to address the difficulties caused by the co-occurrence of antimicrobial and multidrug-resistant bacteria. E. coli and S. aureus were significantly inhibited by L1 and L2. The L1 exhibits 13, 12 and 15 mm, whereas L2 exhibits a 2, 3 and 5 mm zone of inhibition against S. aureus, S. pyogenes and E. coli, respectively. In silico molecular docking of L1 and L2 was performed with bacterial DNA gyrase to establish the intermolecular interactions. Finally, the in vitro cytotoxicity activities of the ligands L1 and L2 have been carried out using drosophila.

Protein interactions, molecular docking, antimicrobial and antifungal studies of terpyridine ligands.

Resistance to antibiotics/antibacterials/antifungals in pathogenic microbes has been developing over the past few decades and has recently become a commonplace public-health peril. Thus, alternative nontoxic potent antibiotic agents are covertly needed to control antibiotic-resistant outbreaks. In an effort to combat the challenges posed by the co-occurrence of multidrug resistance, two terpyridine ligands 4'-(4-N,N'-dimethylaminophenyl)-2,2':6',2″-terpyridine (L1) and 4'-(4-tolyl)-2,2':6',2″-terpyridine (L2) have been designed, prepared and confirmed their structure by spectral studies. Thereafter, antimicrobial assay was performed against gram positive and negative bacterial strains along with fungal strains. Both compounds L1 and L2 exhibited remarkable inhibitory activities against bacteria, Escherichia coli and Staphylococcus aureus at MIC values 6.25 and 3.125 µg/ml, respectively. In addition, in silico molecular docking studies were ascertained with bacterial DNA gyrase and fungal demethylase. Furthermore, both L1 and L2 could bind Bovine Serum Albumin (BSA) protein and binding interaction has been studied with the help of UV-Visible and fluorescence spectroscopy. While fluorescence of BSA unperturbed in the presence of L2, an addition of L1 to the solution of BSA resulted significant quenching. The binding constant calculations at different temperature confirmed that the fluorescence quenching between BSA and L1 is predominantly static in nature. The toxicity of L1 and L2 was checked using Drosophila melanogaster. The toxicity analysis suggest both the dyes are non-cytotoxic in nature.Communicated by Ramaswamy H. Sarma.