Interaction study of monoisoamyl dimercaptosuccinic acid with bovine serum albumin using biophysical and molecular docking approaches

Abstract

Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a lipophilic chelator has been evaluated for its potential use as an antidote in arsenic poisoning. The pharmacokinetics and pharmacodynamics properties of a drug could be understood via study its mechanism of interaction with bovine serum albumin protein (BSA). Therefore, the interaction between MiADMSA with BSA was investigated using various spectroscopic techniques and computational methods. Linear quenching of BSA intrinsic fluorescence intensity with the increasing concentration of MiADMSA was observed in the fluorescence study. Furthermore, synchronous results revealed that MiADMSA slightly changed the conformation of BSA. The binding constant value of the BSA-MiADMSA complex was found 1.60 × 104 M−1 at 298 K. The value of thermodynamic parameters ΔG, ΔH, and ΔS described that the process is spontaneous, endothermic, and hydrophobic forces are involved in the interaction of MiADMSA with BSA. Competitive site marker experiments showed that MiADMSA binds to site-II of BSA. Conformational changes of BSA with the interaction of MiADMSA were apparent by CD, UV–Visible, FT-IR, and 3D fluorescence spectroscopy. To strengthen the experimental findings we have also performed a theoretical study on the BSA-MiADMSA complex. Two sites were identified with docking score of − 6.642 kcal/mol at site IIa and − 3.80 kcal/mol for site IIb via molecular docking study. Molecular dynamics simulation study inferred the stability of the BSA-MiADMSA complex which was analyzed in a long simulation run. The experimental and computational studies have shown the effective binding of MiADMSA with BSA which is essential for the transportation and elimination of a drug from the body.

Chemistry, Pharmacology, and Toxicology of Monoisoamyl Dimercaptosuccinic Acid: A Chelating Agent for Chronic Metal Poisoning

“…Male rats treated with oral MiADMSA (25, 50, and 100 mg/kg showed moderate congestion, hemorrhage and infiltration of mononuclear cells, which caused inflammation, which is a defensive mechanism of the cells. All the changes, which were observed in the liver and kidney, were reversible in nature . Female rats, on the other hand, showed few signs of toxicity in liver and kidneys particularly at the higher dose level while no significant change was observed in the brain variables except for a significant decrease in the thiobarbituric reactive acid reactive substance levels at the lower dose 25 mg/kg.…”

“…All the changes, which were observed in the liver and kidney, were reversible in nature. 116 Female rats, on the other hand, showed few signs of toxicity in liver and kidneys particularly at the higher dose level while no significant change was observed in the brain variables except for a significant decrease in the thiobarbituric reactive acid reactive substance levels at the lower dose 25 mg/kg. No gross pathological changes were observed in these animals.…”

Heme Protein Binding of Sulfonamide Compounds: A Correlation Study by Spectroscopic, Calorimetric, and Computational Methods

“…Fluorescence spectroscopy is an important and useful technique for determining drug–protein interaction and providing information about drug association to proteins. , Various binding mechanism details on the binding site, binding affinity, and structural and conformational adaptations can be studied from fluorescence spectrophotometry studies. − For the binding study of Mb with SMZ and SDZ, the excitation wavelength was examined at 295 nm, which selectively excites the emission maxima at 337 nm. The intrinsic fluorescence is mainly due to tyrosine (Tyr103, Tyr143, Tyr151) and tryptophan (Trp7, Trp14) residues present in Mb, which are subtle for the change in its microenvironment.…”

Interaction Study between ESIPT Fluorescent Lipophile-Based Benzazoles and BSA

“…BSA is composed of a single polypeptide chain of 583 amino acid residues [46] and three domains named I, II, and III, each of which is divided into two subdomains (A and B) [47]. Studies indicate that the main association sites are located in the hydrophobic cavities of the IIA and IIIA subdomains [48]. The BSA structure has two Trp residues, Trp-134 in the first domain, located on the surface of the molecule, and Trp-212 in the IIA subdomain, located in the hydrophobic region of the protein [49,50].…”