JOURNAL OF MOLECULAR STRUCTURE, vol.2022, pp.1-20, 2022 (SCI-Expanded)
Flavonoids have an important place in chemistry and pharmacology. Several flavonoids, especially Quercetin, have the potential to form molecular complexes with nucleic acid structure and have re-cently attracted attention due to their prospective clinical and pharmacological uses. DNA is the main target for a wide variety of therapeutic agents. Therefore, there is great interest in studies of binding small molecules with DNA. The interaction of small molecules with DNA provides a structural guide in rational drug design and the synthesis of new and improved drugs with enhanced selective activity and higher clinical efficacy. Even if newly synthesized candidate drug molecules with small molecular weight are capable of indirectly interacting with DNA, the mechanisms that accomplish this need to be clearly known. In this study, the mechanism of fish sperm double strain deoxyribonucleic acid (dsDNA) binding with Quercetin (QCR) and its two novel sulfonate derivatives (quercetin mesylate (QMS) and quercetin tosylate-A (QTS-A)) were researched. For investigating the interaction between the molecules and dsDNA was studied by analytical (spectrophotometric, viscosimetric, and electrochemical) methods. The interaction of dsDNA and two quercetin sulfonate derivatives were compared with the interaction of the QCR standard after all experimental studies. Moreover, the DNA binding constants Kb were deter-mined using each method. The Kb constants calculated for QCR, QMS, and QTS-A are in harmony for all techniques. The results showed that QCR binds to dsDNA via intercalation mode, while QMS and QTS-A bind through minor groove binding mode. In addition to experimental studies, theoretical studies were conducted at room temperature under physiological conditions (pH 7.4). Molecular docking calcu-lations and molecular dynamics (MD) simulations have been found to be compatible with experimental studies.(c) 2022 Elsevier B.V. All rights reserved.