Insights into the binding of thiosemicarbazone derivatives with human serum albumin: spectroscopy and molecular modelling studies

Abstract

4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl acetate [Ace semi],4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl propanoate [Pro semi] from the family of thiosemicarbazones derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and it is also less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of thiosemicarbazone derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance (r) between donor (HSA) and acceptor (thiosemicarbazone derivative) was estimated according to Forster's theory of non-radiative energy transfer using fluorescence spectroscopy. The binding dynamics has been elaborated using synchronous fluorescence spectroscopy, and the feature of thiosemicarbazone derivative induced structural changes of HSA has been studied by circular dichorism, Fourier transform infrared spectroscopy. Molecular modelling simulations explore the hydrophobic interaction and hydrogen bonding which stabilizes the interaction.

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

“…Figure 3(a) shows the emission decay profile of free HSA and HSA-coumarin derivative complex; each point consists of average photons of respective wavelengths. All the recorded emission profiles of HSA and HSA complex followed the multiexponential decay kinetics, and the average lifetime decay for free HSA was found to be 4.83 ns which is almost equal to previously reported values [21,23]. However, in the case of HSA-coumarin derivative complex, the decay is slightly faster compared to that of free HSA, and the average estimation of the HSA complex is 4.67 ns ( Table 2).…”

“…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.…”

Underlying the Mechanism of 5-Fluorouracil and Human Serum Albumin Interaction: A Biophysical Study

“…. Thus we carried out computational studies to analyse the binding mode of 5-FU with HSA using molecular docking (Glide) and dynamic simulation, which helps us in understanding stability of protein-ligand complex in terms of thermodynamics parameter and docking result of 5-FU with HSA suggest that drug 5-FU favourably binds to lower region of proximal site in sub domain IB and interact with alpha helices H7, H8 and H9 with binding energy -25.45 Kcal/mol (in term of Glide energy) [28][29][30][31]. Uracil ring of 5-FU showed a π -π interaction with Phe149 and His146, hydrogen bond with Tyr 138 and many hydrophobic interactions with HSA ( Figure 10; Table 2).…”

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

“…In general, the interaction of biomolecules with small molecules may have the possibility of hydrogen bonding, hydrophobic interaction, van der Waals interaction, electrostatic forces etc., which can be calculated using von't Hoff plots. Before the suggestion of interaction types between the thiadiazole drug with the EB–ctDNA system, enthalpy (Δ H °), entropy (Δ S °) and free energy changes (Δ G °) need to be calculated using the following equations where R is the gas constant.…”