Interactions of linagliptin, rabeprazole sodium, and their formed complex with bovine serum albumin: Computational docking and fluorescence spectroscopic methods

Abstract

The foremost aim of this thermodynamic study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of linagliptin (LG), rabeprazole sodium (RS), and their 1:1 formed complex by interacting with bovine serum albumin (BSA) at physiological pH 7.4. The molecular interactions of these ligands with the desired biomolecule were substantiated by the spectral quelling of fluorescence intensity of BSA. The fluorescent test and molecular docking revealed that the quenching mechanism was a spontaneous and exothermic static process, and the protein gained its secondary structure due to the interactions. The spectroscopic method was exercised to determine the thermodynamic factors that supported the interactions mediated by van der Waals forces and hydrogen bonds. The activation energy of the formed complex was higher than its precursor drugs while interacting with BSA, and the energy transformation profiles were studied by UV-fluorescence overlaid curves according to Förster resonance energy transfer (FRET) theory. The double log plot verified that these ligands bound with protein at a 1:1 ratio, which was confirmed by the approximately estimated values of the binding parameters. The drastically lower value of the binding constant of the formed complex suggested the lower half-life as well as its triggered elimination rate from the cardiovascular system, which may be an initial indicator of the reduced hypoglycemic property of linagliptin. Moreover, the UV-vis and synchronous fluorescence spectroscopic methods affirmed the conformational changes of the BSA due to drug-protein complexation and polarity alterations in the microenvironment of disparate chromophores of the biomolecule.

Influence of ultrasound on the mechanism of conjugation between epigallocatechin gallate and β‐lactoglobulin for function improvement

“…The fluorescence intensity could be quenched, when tryptophan and tyrosine residues of βLg accessed the quencher, providing a convenient tool to investigate the interaction between proteins and ligands (Swain et al ., 2020). The results of fluorescence quenching can be described in terms of binding affinities (Ka) (Hossain et al ., 2021). Ka is obtained as follows (Yang et al ., 2020): where F 0 and F are the protein's maximal fluorescence intensities in the absence or presence of ligand respectively; Ka is the binding constant; D is the ligand concentration and n is the number of binding sites on a single protein molecule.…”

Ligand-Based Virtual Screening and Molecular Docking of Benzimidazoles as Potential Inhibitors of Triosephosphate Isomerase Identified New Trypanocidal Agents

“…After that, 1604 molecules by molecular docking showed better binding energy than ligand L1. The lead compound of the ten groups obtained from molecular docking analysis showed interactions with amino acid residues previously reported as important for the binding on the Tc TIM interface, such as Tyr102 (A), Tyr103 (A), and Ile69 (B) [ 25 , 26 , 29 , 31 ]. The presence of hydrogen bonds, as well as hydrophobic interactions, also promote the formation of stronger and more robust ligand–protein complexes [ 32 ].…”

“…In the present work, a ligand-based virtual screening (LBVS) from the ZINC15 database using benzimidazole substructure was carried out; the compounds obtained were analyzed by molecular docking, and subsequently, a selection of compounds was made based on the interaction profile and docking score for an in vitro evaluation against trypomastigotes of T. cruzi and a molecular dynamics simulation analysis. Benzimidazole derivatives have been used in drug designing; however, these kinds of compounds have shown some disadvantages such as hepatotoxicity, among others [ 26 , 27 , 28 , 29 , 30 ]. Therefore, in this study, a prediction of the adsorption, distribution, metabolism and excretion (ADME) properties by computational analysis was performed.…”

Chemical and Pharmacological Profiling of Wrightia coccinea (Roxb. Ex Hornem.) Sims Focusing Antioxidant, Cytotoxic, Antidiarrheal, Hypoglycemic, and Analgesic Properties

“…Molecular docking analysis was performed to interpret the interactive profile of the four isolated compounds from W. coccinea with their target proteins. The widely used popular software packages, including PyRx, PyMoL 2.3, and BIOVA Discovery Studio version 4.5, were utilized during for the in silico study of the isolated compounds from W. coccinea according to the semiflexible procedures described in several studies [36][37][38][39][40][41].…”