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。
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.