The efficient synthesis of molecular hybrids including a DNA‐intercalating 9‐anilinoacridine (9‐AnA) core and a methyl triazene DNA‐methylating moiety is described. Nucleophilic aromatic substitution (S_NAr) and electrophilic aromatic substitution (EAS) reactions using readily accessible starting materials provide a quick entry to novel bifunctional anticancer molecules. The chimeras were evaluated for their anticancer activity. Chimera 7b presented the highest antitumor activity at low micromolar IC₅₀ values in antiproliferative assays performed with various cancer cell lines. In comparison, compound 7b outperformed DNA‐intercalating drugs like amsacrine and AHMA. Mechanistic studies of chimera 7b suggest a dual mechanism of action: methylation of the DNA‐repairing protein MGMT associated with the triazene structural portion and Topo II inhibition by intercalation of the acridine core.

中文翻译：

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双作用9-苯胺吖啶甲基三氮烯嵌合体的便利合成和抗癌评价

描述了包括插入 DNA 的 9-苯胺吖啶 (9-AnA) 核心和甲基三氮烯 DNA 甲基化部分的分子杂合体的有效合成。亲核芳香取代 (S _N Ar) 和亲电芳香取代 (EAS) 反应使用容易获得的起始材料提供了快速进入新型双功能抗癌分子的途径。评估嵌合体的抗癌活性。在用各种癌细胞系进行的抗增殖试验中，嵌合体7b在低微摩尔 IC ₅₀值下表现出最高的抗肿瘤活性。相比之下，化合物7b 的表现优于安吖啶和 AHMA 等 DNA 嵌入药物。嵌合体7b 的机理研究 表明双重作用机制：与三氮烯结构部分相关的 DNA 修复蛋白 MGMT 的甲基化和通过吖啶核心的插入抑制 Topo II。