PDF(Pubmed)
Abstract：
Bendamustine (BENDA) is a bifunctional alkylating agent with alkylating and purinergic antitumor activity, which exerts its anticancer effects by direct binding to DNA, but the detailed mechanism of BENDA-DNA interaction is poorly understood. In this paper, the interaction properties of the anticancer drug BENDA with calf thymus DNA (ctDNA) were systematically investigated based on surface-enhanced Raman spectroscopy (SERS) technique mainly using a novel homemade AuNPs/ZnCl2/NpAA (NpAA: nano porous anodic alumina) solid-state substrate and combined with ultraviolet-visible spectroscopy and molecular docking simulation to reveal the mechanism of their interactions. We experimentally compared and studied the SERS spectra of ctDNA, BENDA, and BENDA-ctDNA complexes with different molar concentrations (1:1, 2:1, 3:1), and summarized their important characteristic peak positions, their peak position differences, and hyperchromic/hypochromic effects. The results showed that the binding modes include covalent binding and hydrogen bonding, and the binding site of BENDA to DNA molecules is mainly the N7 atom of G base. The results of this study help to understand and elucidate the mechanism of BENDA at the single-molecule level, and provide guidance for the further development of effective new drugs with low toxicity and side effects.
摘要：
苯达莫司汀（BENDA）是一种具有烷化剂和嘌呤能抗肿瘤活性的双功能烷化剂，通过与DNA直接结合发挥抗癌作用，但是BENDA-DNA相互作用的详细机制知之甚少。在本文中,基于表面增强拉曼光谱（SERS）技术，主要使用新型的自制AuNPs/ZnCl2/NpAA（NpAA：纳米多孔阳极氧化铝）固态基底，并结合紫外可见光谱和分子对接模拟，系统地研究了抗癌药物BENDA与小牛胸腺DNA（ctDNA）的相互作用机理。我们通过实验比较和研究了ctDNA的SERS光谱，本达,和不同摩尔浓度（1：1，2：1，3：1）的BENDA-ctDNA复合物，并总结了它们的重要特征峰位置，它们的峰值位置差异，和增色/减色效应。结果表明，结合模式包括共价键和氢键，BENDA与DNA分子的结合位点主要是G碱基的N7原子。这项研究的结果有助于在单分子水平上理解和阐明BENDA的机制，并为进一步开发低毒、副作用的有效新药提供指导。
