Compared with single-targeted therapy, the design and synthesis of heterozygous molecules is still a significant challenge for the discovery of antitumor drugs. Quinone oxidoreductase-1 (NQO1) is a potential target for selective cancer therapy due to its overexpression in many cancer cells and its unique bioredox properties. Based on the principle of combinatorial drug design, we successfully synthesized a new hybrid molecules 13 with an indolequinone structure. We found that the synthesized compounds exhibited much higher cytotoxicity against the tested cancer cells than free drugs. Further mechanism studies confirmed that compound 13 induced cell apoptosis was achieved by regulating p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase.

中文翻译：

---

吲哚醌连接吴茱萸碱与厄洛替尼组合物的设计、合成及生物活性评价

与单靶向治疗相比，杂合分子的设计和合成仍然是抗肿瘤药物发现的重大挑战。醌氧化还原酶-1 (NQO1) 因其在许多癌细胞中过度表达及其独特的生物氧化还原特性而成为选择性癌症治疗的潜在靶点。基于组合药物设计原理，我们成功合成了具有吲哚醌结构的新型杂化分子13。我们发现合成的化合物对测试的癌细胞表现出比游离药物更高的细胞毒性。进一步的机制研究证实，化合物13诱导细胞凋亡是通过调节p53依赖性线粒体途径和细胞周期停滞在G0/G1期来实现的。