Waihenya Simon, Şenel Pelin, Osonga Francis J, Erdoğan Taner, Altay Filiz, Gölcü Ayşegül, Sadik Omowunmi A
Department of Chemistry, Center for Research in Advanced Sensing Technologies & Environmental Sustainability (CREATES), State University of New York at Binghamton, P.O. Box 6000, Binghamton, New York 13902-6000, United States.
Department of Chemistry, Faculty of Sciences and Letters, Istanbul Technical University, Istanbul 34469, Turkey.
ACS Omega. 2021 Feb 19;6(8):5124-5137. doi: 10.1021/acsomega.0c02612. eCollection 2021 Mar 2.
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, respectively. The electrochemical binding constants were determined to be (1.05 × 10) ± 0.04, (0.47 × 10) ± 0.02, and (8.13 × 10) ± 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 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.
DNA结合研究对于设计更好的药物化合物至关重要，因为化合物与小沟中的双链DNA结合在药物发现中至关重要。尽管仅进行了一项关于芹菜素（APG）DNA结合模式的体外研究，但尚未有电化学和理论研究报道。我们在此报告APG以及一类新型的磺酰胺修饰黄酮类化合物，芹菜素二磺酰胺（ADSAM）和芹菜素三磺酰胺（ATSAM）与脱氧核糖核酸（DNA）的结合相互作用机制。本研究使用了多光谱仪器技术，包括紫外可见吸收光谱、热变性、荧光光谱和傅里叶变换红外（FTIR）光谱，以及电化学和粘度测量方法。此外，在生理条件（pH 7.4）下于室温进行了分子对接研究。分子对接研究表明，在所有情况下，能量最低的对接构象都与DNA的小沟结合，并且芹菜素-DNA复合物通过几个氢键得以稳定。此外，π-硫相互作用在ADSAM-DNA和ATSAM-DNA复合物的稳定中发挥了作用。发现APG-DNA、ADSAM-DNA和ATSAM-DNA复合物能量最低的对接构象（目录（TOC）示意图）的结合亲和力分别为-8.2、-8.5和-8.4 kcal/mol。APG、ADSAM和ATSAM的电化学结合常数分别测定为(1.05×10)±0.04、(0.47×10)±0.02和(8.13×10)±0.03（所有测试均重复进行三次，并表示为平均值和标准偏差（SD））。通过所有技术计算得到的APG、ADSAM和ATSAM的常数相互吻合。由于在APG结构中引入了氨基磺酸二甲酯基团，在ADSAM-dsDNA和ATSAM-dsDNA复合物中，除了氢键外，π-硫相互作用也有助于配体-DNA复合物的稳定。这项工作提供了新的见解，可能会推动前瞻性药物和疫苗的开发。
