Mushtaq Alia, Naseer Muhammad Moazzam
Department of Chemistry, Quaid-i-Azam University Islamabad 45320 Pakistan
RSC Adv. 2025 Mar 18;15(11):8443-8455. doi: 10.1039/d5ra00899a. eCollection 2025 Mar 17.
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 -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 groove-binding modes with SS-DNA. The binding constants ( ) of synthesized hybrids with SS-DNA calculated from the Benesi-Hildebrand plot, ranged from 10 to 10 M, with compound 7f exhibiting the highest binding constant (9.51 × 10 M) at 298 K, surpassing the reference cabozantinib. The Gibbs free energy change in the binding interaction of 7f, was found to be Δ = -34.1 kJ mol indicating a spontaneous binding process. The molecular docking results supported experimental findings with a docking score of -10.3 kcal mol for 7f, highlighting hydrophobic and hydrogen bonding interactions within the AT-rich region of DNA grooves. In addition, DFT and studies provided insights into the charge density of structures and drug-likeness, hence the -triazine-isatin hybrid core holds promise as a potential therapeutic agent.
DNA结合是开发新型抗癌药物的关键决定因素，因为它在许多化疗药物的作用机制中起着关键作用。在本研究中，合成了一系列新型的三嗪-异吲哚酮杂化物（7a-f），并在生理条件（pH 7.4）下使用紫外可见吸收光谱研究了它们与鲑鱼精DNA（SS-DNA）的结合相互作用。实验结果表明，通过吸收和强度变化，这些杂化物与SS-DNA具有很强的DNA结合亲和力，呈现出沟槽结合模式。根据Benesi-Hildebrand图计算，合成杂化物与SS-DNA的结合常数（）范围为10至10 M，化合物7f在298 K时表现出最高的结合常数（9.51×10 M），超过了参考药物卡博替尼。发现7f结合相互作用中的吉布斯自由能变化为Δ = -34.1 kJ mol，表明这是一个自发的结合过程。分子对接结果支持了实验结果，7f的对接分数为-10.3 kcal mol，突出了DNA沟槽富含AT区域内的疏水和氢键相互作用。此外DFT和研究提供了对结构电荷密度和药物相似性的见解，因此三嗪-异吲哚酮杂化核心有望成为一种潜在的治疗剂。
