许多小分子通过与 DNA 相互作用发挥抗肿瘤作用，从而影响 DNA 复制、转录、减数分裂和基因重组等过程。已知苯并菲啶和原小檗碱生物碱可结合 DNA 并表现出许多药理活性。在本研究中，我们对这两类生物碱与 G 四链体 (G4) DNA 和双链 DNA (dsDNA) 之间的相互作用进行了比较分析。原小檗碱生物碱与 G4s 的结合亲和力高于与 dsDNA 的结合力，而苯并菲啶生物碱对 dsDNA 的结合能力明显更强，尤其是在富含 AT 碱基对的区域。苯并菲啶生物碱对各种癌细胞也表现出更强的毒性。与原小檗碱生物碱相比，苯并菲啶生物碱在抑制细胞DNA和RNA合成、将细胞周期阻滞在G2/M期、诱导细胞凋亡、导致细胞内DNA损伤方面表现出更强的活性。鉴于在细胞周期的大部分时间里，dsDNA 是细胞内 DNA 的主要形式，苯并菲啶生物碱的显着抗增殖活性可能部分归因于它们对 dsDNA 的较高结合亲和力，从而对细胞增殖产生更显着的影响。这些发现对于了解异喹啉生物碱的生物活性及其抗肿瘤应用具有重要意义。

Numerous small molecules exert antitumor effects by interacting with DNA, thereby influencing processes, such as DNA replication, transcription, meiosis, and gene recombination. Benzophenanthridine and protoberberine alkaloids are known to bind DNA and exhibit many pharmacological activities. In this study, we conducted a comparative analysis of the interactions between these two classes of alkaloids with G-quadruplex (G4) DNA and double-stranded DNA (dsDNA). Protoberberine alkaloids showed a greater affinity for binding with G4s than with dsDNA, while benzophenanthridine alkaloids exhibited a significantly stronger binding capacity for dsDNA, especially in regions that are rich in AT base pairs. Benzophenanthridine alkaloids also exhibited much stronger toxicity to various cancer cells. Compared with protoberberine alkaloids, benzophenanthridine alkaloids displayed much stronger activity in inhibiting cellular DNA and RNA synthesis, arresting the cell cycle in the G2/M phase, inducing cell apoptosis, and leading to intracellular DNA damage. Given that dsDNA constitutes the predominant form of DNA within cells for the majority of the cell cycle, the significant antiproliferative activity of benzophenanthridine alkaloids could be attributed, in part, to their higher binding affinity for dsDNA, thereby exerting a more significant impact on cellular proliferation. These findings have valuable implications for understanding the biological activities of isoquinoline alkaloids and their antitumor applications.