Investigation of the ability of 3-((4-chloro-6-methyl pyrimidin-2-yl)amino) isobenzofuran-1(3H)-one to bind to double-stranded deoxyribonucleic acid

Phthalides represent a notable category of secondary metabolites that are prevalent in various plant species, certain fungi, and liverworts. The significant pharmacological properties of these compounds have led to the synthesis of a novel phthalide derivative. The current study focuses on investigating the binding interactions of a newly synthesized 3-substituted phthalide derivative, specifically 3-((4-chloro-6-methyl pyrimidine-2-yl)amino) isobenzofuran-1(3H)-one (Z11), with double-stranded deoxyribonucleic acid (dsDNA). Research in the pharmaceutical and biological fields aimed at developing more potent DNA-binding agents must take into account the mechanisms by which these newly synthesized compounds interact with DNA. This investigation seeks to explore the binding dynamics between dsDNA and our compound through a variety of analytical techniques, such as electrochemistry, UV spectroscopy, fluorescence spectroscopy, and thermal denaturation. The binding constant (K_b) of Z11 with DNA was determined using both spectroscopic and voltammetric approaches. The research revealed that Z11 employs a groove binding mechanism to associate with dsDNA. To further explore the interactions between Z11 and dsDNA, the study utilized density functional theory (DFT) calculations, molecular docking, and molecular dynamics simulations. These analyses aimed to ascertain the potential for a stable complex formation between Z11 and dsDNA. The results indicate that Z11 is situated within the minor groove of the dsDNA, demonstrating the ability to establish a stable complex. Furthermore, the findings imply that both π-alkyl interactions and hydrogen bonding play significant roles in the stabilization of this complex. Graphical Abstract: (Figure presented.)