Hajian Reza, Hossaini Parvin, Mehrayin Zahra, Woi Pei Meng, Shams Nafiseh
Department of Chemistry, College of Science, Gachsaran Branch, Islamic Azad University, 75818-63876, Iran.
Institute of Advanced Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
J Pharm Anal. 2017 Jun;7(3):176-180. doi: 10.1016/j.jpha.2017.01.003. Epub 2017 Jan 11.
In this study, the molecular interactions between valrubicin, an anticancer drug, and fish sperm DNA have been studied in phosphate buffer solution (pH 7.4) using UV-Vis spectrophotometry and cyclic voltammetry techniques. Valrubicin intercalated into double stranded DNA under a weak displacement reaction with methylene blue (MB) molecule in a competitive reaction. The binding constant () of valrubicin-DNA was determined as 1.75×10 L/mol by spectrophotometric titration. The value of non-electrostatic binding constant ([Formula: see text]) was almost constant at different ionic strengths while the ratio of [Formula: see text]/ increased from 4.51% to 23.77%. These results indicate that valrubicin binds to ds-DNA via electrostatic and intercalation modes. Thermodynamic parameters including ΔH, ΔS and ΔG for valrubicin-DNA interaction were determined as -25.21×10 kJ/mol, 1.55×10 kJ/mol K and -22.03 kJ/mol, respectively. Cyclic voltammetry study shows a pair of redox peaks for valrubicin at 0.45 V and 0.36 V (vs. Ag/AgCl). The peak currents decreased and peak positions shifted to positive direction in the presence of DNA, showing intercalation mechanism due to the variation in formal potential.
在本研究中,使用紫外可见分光光度法和循环伏安法技术,在磷酸盐缓冲溶液(pH 7.4)中研究了抗癌药物缬柔比星与鱼精DNA之间的分子相互作用。在与亚甲蓝(MB)分子的竞争反应中,缬柔比星在弱置换反应下插入双链DNA。通过分光光度滴定法测定缬柔比星-DNA的结合常数()为1.75×10 L/mol。在不同离子强度下,非静电结合常数([公式:见正文])的值几乎恒定,而[公式:见正文]/的比值从4.51%增加到23.77%。这些结果表明缬柔比星通过静电和插入模式与双链DNA结合。缬柔比星-DNA相互作用的热力学参数,包括ΔH、ΔS和ΔG,分别测定为-25.21×10 kJ/mol、1.55×10 kJ/mol K和-22.03 kJ/mol。循环伏安法研究表明,缬柔比星在0.45 V和0.36 V(相对于Ag/AgCl)处有一对氧化还原峰。在DNA存在下,峰电流降低,峰位置向正方向移动,由于形式电位的变化显示出插入机制。