Sharifi-Rad Atena, Amiri-Tehranizadeh Zeinab, Talebi Atiye, Nosrati Niknaz, Medalian Morvarid, Pejhan Mahtab, Hamzkanloo Nazanin, Saberi Mohammad Reza, Mokaberi Parisa, Chamani Jamshidkhan
Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Bioimpacts. 2023;13(1):5-16. doi: 10.34172/bi.2022.23592. Epub 2022 Apr 30.
Here, the interaction behavior between propyl acridones (PA) and calf thymus DNA (ct-DNA) has been investigated to attain the features of the binding behavior of PA with ct-DNA, which includes specific binding sites, modes, and constants. Furthermore, the effects of PA on the conformation of ct-DNA seem to be quite significant for comprehending the medicine's mechanism of action and pharmacokinetics. The project was accomplished through means of absorbance studies, fluorescence spectroscopy, circular dichroism, viscosity measurement, thermal melting, and molecular modeling techniques. The intercalation of PA has been suggested by fluorescence quenching and viscosity measurements results while the thermal melting and circular dichroism studies have confirmed the thermal stabilization and conformational changes that seem to be associated with the binding. The binding constants of ct-DNA-PA complex, in the absence and presence of EMF, have been evaluated to be 6.19 × 10 M and 2.95 × 10 M at 298 K, respectively. In the absence of EMF, the ∆H and ∆S values that occur in the interaction process of PA with ct-DNA have been measured to be -11.81 kJ.mol and 51.01 J.molK, while in the presence of EMF they were observed to be -23.34 kJ.mol and 7.49 J.molK, respectively. These numbers indicate the involvement of multiple non-covalent interactions in the binding procedure. In a parallel study, DNA-PA interactions have been monitored by molecular dynamics simulations; their results have demonstrated DNA stability with increasing concentrations of PA, as well as calculated bindings of theoretical ΔG. The complex formation between PA and ct-DNA has been investigated in the presence and absence of EMF through the multi spectroscopic techniques and MD simulation. These findings have been observed to be parallel to the results of KI and NaCl quenching studies, as well as the competitive displacement with EB and AO. According to thermodynamic parameters, electrostatic interactions stand as the main energy that binds PA to ct-DNA. Regarding the cases that involve the T of ct-DNA, EMF has proved to increase the stability of binding between PA and ct-DNA.
在此，对丙基吖啶酮（PA）与小牛胸腺DNA（ct-DNA）之间的相互作用行为进行了研究，以了解PA与ct-DNA结合行为的特征，包括特异性结合位点、模式和常数。此外，PA对ct-DNA构象的影响对于理解该药物的作用机制和药代动力学似乎相当重要。该项目通过吸光度研究、荧光光谱、圆二色性、粘度测量、热熔和分子建模技术完成。荧光猝灭和粘度测量结果表明PA发生了插入作用，而热熔和圆二色性研究证实了似乎与结合相关的热稳定性和构象变化。在298K时，在不存在和存在电磁场（EMF）的情况下，ct-DNA-PA复合物的结合常数分别评估为6.19×10⁶M和2.95×10⁶M。在不存在EMF的情况下，PA与ct-DNA相互作用过程中出现的∆H和∆S值经测量分别为-11.81kJ·mol⁻¹和51.01J·mol⁻¹K，而在存在EMF的情况下，观察到它们分别为-23.34kJ·mol⁻¹和7.49J·mol⁻¹K。这些数值表明在结合过程中涉及多种非共价相互作用。在一项平行研究中，通过分子动力学模拟监测了DNA-PA相互作用；其结果表明随着PA浓度的增加DNA稳定性增强，并计算了理论∆G的结合情况。通过多光谱技术和分子动力学模拟研究了在存在和不存在EMF的情况下PA与ct-DNA之间的复合物形成。观察到这些发现与KI和NaCl猝灭研究的结果以及与EB和AO的竞争性置换结果相似。根据热力学参数，静电相互作用是将PA与ct-DNA结合的主要能量。关于涉及ct-DNA的T的情况，已证明EMF可增加PA与ct-DNA之间结合的稳定性。
