Evaluation of the binding effect and cytotoxicity assay of 2‐Ethyl‐5‐(4‐methylphenyl) pyramido pyrazole ophthalazine trione on calf thymus DNA: spectroscopic, calorimetric, and molecular dynamics approaches

Abstract

With advances in new drug therapies, it is essential to understand the interactions between drugs and target molecules. In this study, we applied multiple spectroscopic techniques including absorbance, fluorescence, circular dichroism spectroscopy, viscosity, thermal melting, calorimetric, and molecular dynamics (MD) simulation to study the interaction between 2-Ethyl-5-(4-methylphenyl) pyramido pyrazole ophthalazine trione (PPF) and calf thymus DNA (ct DNA) in the absence or presence of histone H1. PPF exhibits a high binding affinity towards ct DNA in binary and ternary systems. In addition, the result for the binding constant was observed within the range 10 4 M À1 achieved through fluorescence quenching data, while the values for enthalpy and entropy changes for ct DNA-PPF and (ct DNA-H1) PPF complexes were measured to be À72.54 kJ.mol À1 , À161.14 J.mol À1 K À1 , À85.34 kJ.mol À1 , and À19.023 J.mol À1 K À1 , respectively. Furthermore, in accordance with circular dichroism spectra, the inducement of ct DNA structural changes was observed during binding of PPF and H1 in binary and ternary system forms. The essential roles of hydrogen bonding and van der Waals forces throughout the interaction were suggested using thermodynamic parameters. According to the obtained data, the interaction mode of ct DNA-PPF and (ct DNA-H1) PPF complexes was intercalation binding. Suggested by the MD simulation study, the ct DNA-H1 complex caused a reduction in the stability of the DNA structure in the presence or absence of ligand, which demonstrated that PPF as an intercalating agent can further distort the structure. The information achieved from this study will be very helpful in understanding the effects of PPF on the conformational state of ct DNA in the absence or presence of the H1 molecule, which seems to be quite significant for clarifying the mechanisms of action and its pharmacokinetics.

Study on the binding behavior and functional properties of soybean protein isolate and β-carotene

“…As described in section “Fluorescence quenching,” different addition ratios of β-carotene caused different changes in the conformation of SPI. Moreover, with the increase of K a value, the binding affinity also raised, meaning a more stable bonding occurred, indicating an efficient interaction between SPI and BC that could be an excellent carrier in vivo being to take shape, which is consistence with the findings of Chamani et al ( 44 , 45 ).…”

Molecular recognition between bacterial phosphorothioate DNA and sulfur-binding domain (SBD): competition between the water cage and chalcogen-hydrophobic packet

“…Several experimental approaches including calorimetry and spectroscopy were used to evaluate the binding affinity among biomolecules; [26][27][28][29] recently, molecular modeling approaches have also prevailed to illustrate the detailed structures inside. [30][31][32] Here, we employed all-atom molecular dynamics (MD) simulations, alchemical free energy calculations, quantum chemical calculations, and non-covalent interaction (NCI) analysis, to extensively quantify the S-O swap effects in the molecular recognition. We also performed fluorescence polarization assays to validate our computational predictions.…”

A novel angiotensin-I-converting enzyme inhibitory peptide from oyster: Simulated gastro-intestinal digestion, molecular docking, inhibition kinetics and antihypertensive effects in rats

“…Various spectroscopy methods are widely used to reveal molecular interactions, such as spectrophotometers, fluorescence spectroscopy, etc., circular dichroism (CD) ( 14 – 17 ). In addition, molecular docking, a simulation algorithm is also used to calculate the physical and chemical properties, spatial structure, and biological activity of protein or peptides ( 18 – 20 ). Based on the lock and key principle of ligand and receptor, molecular docking can calculate the detailed interaction information between receptor and ligand, to screen out potentially effective ACEI peptides ( 21 ).…”