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

Simon Waihenya, Pelin Şenel, Francis J. Osonga, Taner Erdoǧan, Filiz Altay, Ayşegül Gölcü, Omowunmi A. Sadik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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 Kb 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 Kb 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.

Original languageEnglish
Pages (from-to)5124-5137
Number of pages14
JournalACS Omega
Issue number8
Publication statusPublished - 2 Mar 2021

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society.


The authors acknowledge the National Science Foundation Grant # IOS-1543944 and Bill & Melinda Gates Foundation for funding. The authors thank Istanbul Technical University for all experimental conditions (Lab L-105 belonging to Prof. Gölcü).

FundersFunder number
National Science FoundationIOS-1543944
Bill and Melinda Gates Foundation


    Dive into the research topics of 'Mechanism of Interactions of dsDNA Binding with Apigenin and Its Sulfamate Derivatives Using Multispectroscopic, Voltammetric, and Molecular Docking Studies'. Together they form a unique fingerprint.

    Cite this