Mechanism of Interactions of dsDNA Binding with Apigenin and Its Sulfamate Derivatives Using Multispectroscopic, Voltammetric, and Molecular Docking Studies

Abstract

DNA binding investigations are critical for designing better pharmaceutical compounds since the binding of a compound to dsDNA in the minor groove is critical in drug discovery. Although only one in vitro study on the DNA binding mode of apigenin (APG) has been conducted, there have been no electrochemical and theoretical studies reported. We hereby report the mechanism of binding interaction of APG and a new class of sulfonamide-modified flavonoids, apigenin disulfonamide (ADSAM) and apigenin trisulfonamide (ATSAM), with deoxyribonucleic acid (DNA). This study was conducted using multispectroscopic instrumentation techniques, which include UV–vis absorption, thermal denaturation, fluorescence, and Fourier transform infrared (FTIR) spectroscopy, and electrochemical and viscosity measurement methods. Also, molecular docking studies were conducted at room temperature under physiological conditions (pH 7.4). The molecular docking studies showed that, in all cases, the lowest energy docking poses bind to the minor groove of DNA and the apigenin–DNA complex was stabilized by several hydrogen bonds. Also, π–sulfur interactions played a role in the stabilization of the ADSAM–DNA and ATSAM–DNA complexes. The binding affinities of the lowest energy docking pose (schematic diagram of table of content (TOC)) of APG–DNA, ADSAM–DNA, and ATSAM–DNA complexes were found to be −8.2, −8.5, and −8.4 kcal mol–1, respectively. The electrochemical binding constants K b were determined to be (1.05 × 105) ± 0.04, (0.47 × 105) ± 0.02, and (8.13 × 105) ± 0.03 for APG, ADSAM, and ATSAM, respectively (all of the tests were run in triplicate and expressed as the mean and standard deviation (SD)). The K b constants calculated for APG, ADSAM, and ATSAM are in harmony for all techniques. As a result of the incorporation of dimethylsulfamate groups into the APG structure, in the ADSAM–dsDNA and ATSAM–dsDNA complexes, in addition to hydrogen bonds, π–sulfur interactions have also contributed to the stabilization of the ligand–DNA complexes. This work provides new insights that could lead to the development of prospective drugs and vaccines.

Elucidation of DNA-Eltrombopag Binding: Electrochemical, Spectroscopic and Molecular Docking Techniques

“…This binding significantly increases the thermal denaturation temperature of dsDNA. In contrast, groove-binding agents cannot raise the denaturation temperature of dsDNA much, which we have confirmed in several studies [ 26 , 27 , 28 , 29 ]. Table 2 shows T m values based on the interaction of dsDNA with different agents.…”

Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes

“…Furthermore, the affinity of the complexes for the biomolecule can be evaluated applying Eq. ( 1 ) [ 51 ]: [DNA] = concentration of DNA in base, ε a = apparent extinction coefficient obtained from A obs /[complex], ε f = extinction coefficient of the DNA-free complex solution, ε b = extinction coefficient of the DNA-bound complex solution, K b = intrinsic binding constant.…”

“…Furthermore, the affinity of the complexes for the biomolecule can be evaluated applying Eq. ( 1) [51]:…”

The Role of Selected Natural Biomolecules in Sperm Production and Functionality

“…It has been proposed that the antioxidant behavior of API stems from its ability to scavenge free radicals and chelate metal ions [ 247 ]. An important aspect of API lies in its ability to be taken up by cells easily and to bind to DNA via both intercalation and external binding, which forms API-DNA complexes and protects DNA from oxidative stress within cells [ 242 , 248 ].…”