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抗癌药物伊立替康与双链DNA和单链DNA相互作用的比较研究。

Comparative studies on the interaction of anticancer drug irinotecan with dsDNA and ssDNA.

作者信息

Temerk Yassien, Ibrahim Mohamed, Ibrahim Hossieny, Schuhmann Wolfgang

机构信息

Chemistry Department, Faculty of Science, Assiut University Assiut Egypt

Department of Clinical Pharmacy Research, Institute for Research and Medical Consultation, Imam Abdulrahman Bin Faisal University P.O. Box 1982 Dammam 31441 Saudi Arabia.

出版信息

RSC Adv. 2018 Jul 16;8(45):25387-25395. doi: 10.1039/c8ra03231a.

Abstract

A systematic comparative study on the binding of anticancer drug irinotecan (Irino) with dsDNA and ssDNA was investigated in phosphate buffer solutions using voltammetric and spectroscopic methods. The voltammetric results show that the Irino molecule, acting as an intercalator, is inserted into the base stacking domain of the DNA double helix and the strength of interaction is independent of the ionic strength. The hyperchromic effect observed in the UV-visible spectra of Irino in the presence of dsDNA provided the evidence for the intercalation of the drug chromophore with dsDNA base. The interaction mode of Irino molecules with ssDNA is electrostatic attraction negative phosphate on the exterior of the ssDNA with Irino. The binding constants, stoichiometric coefficients and thermodynamic parameters of Irino-dsDNA and Irino-ssDNA complexes were evaluated. The magnitude of changes in Δ , Δ and Δ indicated that the binding process of Irino with ssDNA was more affected than that with dsDNA. The decrease of the peak current of Irino was proportional to DNA concentration, which was applied for determination of dsDNA and ssDNA concentration. The achieved limits of detection of dsDNA and ssDNA were 5.49 × 10 and 1.87 × 10 M, respectively.

摘要

采用伏安法和光谱法,在磷酸盐缓冲溶液中研究了抗癌药物伊立替康(Irino)与双链DNA(dsDNA)和单链DNA(ssDNA)结合的系统比较研究。伏安法结果表明,作为嵌入剂的Irino分子插入到DNA双螺旋的碱基堆积区域,且相互作用强度与离子强度无关。在dsDNA存在下,Irino的紫外可见光谱中观察到的增色效应为药物发色团与dsDNA碱基的嵌入提供了证据。Irino分子与ssDNA的相互作用模式是静电吸引——ssDNA外部带负电的磷酸基团与Irino之间的作用。评估了Irino-dsDNA和Irino-ssDNA复合物的结合常数、化学计量系数和热力学参数。Δ 、Δ 和Δ 的变化幅度表明,Irino与ssDNA的结合过程比与dsDNA的结合过程受影响更大。Irino的峰电流降低与DNA浓度成正比,这可用于测定dsDNA和ssDNA的浓度。dsDNA和ssDNA的检测限分别为5.49×10 和1.87×10 M。

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