Determination on the binding of thiadiazole derivative to human serum albumin: a spectroscopy and computational approach

Abstract

4-[3-acetyl-5-(acetylamino)-2,3-dihydro-1,3,4-thiadiazole-2-yl]phenyl benzoate from the family of thiadiazole derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of thiadiazole derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance, r between the donor (HSA) and acceptor (thiadiazole derivative) was estimated according to Forster's theory of non-radiative energy transfer. The Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) changes of temperature-dependent K was calculated, which explains that the reaction is spontaneous and exothermic. The microenvironment of HSA have also been studied using synchronous fluorescence spectroscopy, and the feature of thiadiazole derivative-induced structural changes of HSA have been carried using Fourier transform infrared spectroscopy and the Molecular modelling simulations explore the hydrophobic and hydrogen bonding interactions.

4-Hydroxycoumarin Derivative:N-(diphenylmethyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide Interaction with Human Serum Albumin

“…Secondary structure calculations were carried out using the DichroWeb (http://dichroweb.cryst.bbk.ac.uk/html/home. shtml) online tool for the free HSA that consists of ∼54.2% α-helix, ∼22.1% β sheets, and 16.3% of the random coil, which are almost comparable with previously published data [17,24].…”

“…e emission spectrum of HSA (1 µM) and various concentrations of the coumarin derivative (0-3.6 µM) is shown in Figure 2(a), and it is indicated that there is a decrease without a shift in emission maximum of the HSA-coumarin derivative complex. Hence, we may conclude that fluorescence quenching occurs due to the presence of the coumarin derivative [17].…”

“…where R is the gas constant and T is the temperature, and here, three different temperatures are used: 293 K, 298 K, and 303 K. According to Ross and Subramanian [17,21,22], the enthalpy change (ΔH°) and entropy change (ΔS°) tabulated in Table 1 indicate that (ΔH°< 0 and ΔS°> 0) type of interaction between HSA and the coumarin derivative complex is maybe due to the electrostatic interaction.…”

Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

“…The binding of CDX enantiomers in HSA subdomain IIIA present differences concerning the number of hydrogen interactions. For example, the complex ( R )-CDX1-HSA is stabilized by three hydrogen-bond interactions with residues Leu-430, Ser-489, and Asn-391, already described as being involved in the binding of drugs to HSA [57,58,59], whereas (S)-CDX1 lacks those interactions (Figure 3B). Therefore, there is concordance between in silico and in vitro studies, as enantiosselectivity can be found on the binding of CDX1 to HSA.…”

A cytotoxicity, optical spectroscopy and computational binding analysis of 4‐[3‐acetyl‐5‐(acetylamino)‐2‐methyl‐2,3‐dihydro‐1,3,4‐thiadiazole‐2‐yl]phenyl benzoate in calf thymus DNA

“…4‐[3‐Acetyl‐5‐(acetylamino)‐2‐methyl‐2,3‐dihydro‐1,3,4‐thiadiazole‐2‐yl]phenyl benzoate (thiadiazole derivative) drug was synthesized according to the previous literature already reported (Figure ).…”