DNA与小分子的结合在设计更有效的抗癌药物方面起着重要作用。已合成并进行了全面表征的五种不同链长度的小檗碱衍生物（BI）与牛胸腺DNA的结合研究，采用多种生物物理技术进行了实验。BI与牛胸腺DNA的结合亲和力随链长度增加而增强。从紫外可见光谱分析中获得的结合常数值分别为BI1为1.84×105，BI2为2.01×105，BI3为1.51×106，BI4为3.66×106，BI5为6.68×106。从圆二色谱和黏度测定的实验中揭示了部分插入结合和DNA螺旋强大的稳定作用。从等温热滴定实验揭示了BI1、BI2、BI3、BI4和BI5与牛胸腺DNA的结合受到明显的正熵和负焓改变的促进，其中BI5表现出最高的自发性。随着链长度的增加，结合由更强的熵项驱动，更高的结合常数表明所有这些相互作用都涉及疏水力。小檗碱-咪唑衍生物与牛胸腺DNA的高结合亲和力可能有助于新药设计。Copyright © 2023. Published by Elsevier B.V.

DNA binding with small molecule plays an important role in the designing of various anticancer drugs with greater efficacy. The five 9-O-imidazolyl alkyl berberine derivatives (BI) of different chain length has been synthesized and fully characterized. The binding study of calf thymus DNA with these newly synthesized berberine derivative was performed using various biophysical techniques. The binding affinity of BI to calf thymus DNA increased with increasing the chain length. The binding constant value obtained from UV-Vis spectral analysis was 1.84x105for BI1, 2.01x105for BI2, 1.51 × 106 for BI3, 3.66 × 106 for BI4, 6.68 × 106. Partial intercalative binding with strong stabilization of the DNA helix was revealed from circular dichroism spectral study and viscosity measurement. From the ITC experiment it was revealed that the bindings of BI1, BI2, BI3, BI4 and BI5 to calf thymus DNA were favoured by a large positive favourable entropy and negative enthalpy change and the highest spontaneity found for BI5. With the increase in chain length the binding was driven by a stronger entropy term with a higher binding constant indicates involvement of hydrophobic force for all these interaction. High binding affinities of calf thymus DNA with berberine-imidazole derivatives might be helpful for new drug design.Copyright © 2023. Published by Elsevier B.V.