Synthesis and DNA binding studies of novel triazine-isatin hybrids: experimental and computational insights

DNA binding is a crucial determinant in developing novel anticancer agents, as it plays a key role in the mechanism of action for many chemotherapeutic drugs. In this study, a series of novel <i>s</i>-triazine-isatin hybrids (7a-f) was synthesized, and their binding interactions with salmon sperm DNA (SS-DNA) were investigated under physiological conditions (pH 7.4) using UV-vis absorption spectroscopy. The experimental findings demonstrated strong DNA-binding affinity through absorption and intensity shifts <i>via</i> groove-binding modes with SS-DNA. The binding constants (<i>K</i> _b) of synthesized hybrids with SS-DNA calculated from the Benesi-Hildebrand plot, ranged from 10⁴ to 10⁵ M^-1, with compound 7f exhibiting the highest binding constant (9.51 × 10⁵ M^-1) at 298 K, surpassing the reference cabozantinib. The Gibbs free energy change in the binding interaction of 7f, was found to be Δ<i>G</i> = -34.1 kJ mol^-1 indicating a spontaneous binding process. The molecular docking results supported experimental findings with a docking score of -10.3 kcal mol^-1 for 7f, highlighting hydrophobic and hydrogen bonding interactions within the AT-rich region of DNA grooves. In addition, DFT and <i>in silico</i> studies provided insights into the charge density of structures and drug-likeness, hence the <i>s</i>-triazine-isatin hybrid core holds promise as a potential therapeutic agent.