Targeting G-quadruplex structures is currently viewed as a promising anticancer strategy. Searching for potent and selective G-quadruplex binders, here we describe a small series of new monohydrazone derivatives designed as analogues of a lead which was proved to stabilize G-quadruplex structures and increase R loop levels in human cancer cells. To investigate the G-quadruplex binding properties of the new molecules, in vitro biophysical studies were performed employing both telomeric and oncogene promoter G-quadruplex-forming sequences. The obtained results allowed the identification of a highly selective G-quadruplex ligand that, when studied in human cancer cells, proved to be able to stabilize both G-quadruplexes and R loops and showed a potent cell killing activity associated with the formation of micronuclei, a clear sign of genome instability.

中文翻译：

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基于一hydr的G四联体选择性配体在人类癌细胞中引起DNA损伤和基因组不稳定。

目前，靶向G-四链体结构是一种有前途的抗癌策略。为了寻找有效的和选择性的G-四链体结合剂，我们在此描述了一系列新的一hydr衍生物，它们被设计为铅的类似物，被证明可以稳定G-四链体结构并增加人类癌细胞中的R环水平。在体外研究新分子的G-四链体结合特性使用端粒和癌基因启动子G-四链体形成序列进行了生物物理研究。获得的结果可以鉴定出高度选择性的G-四链体配体，该配体在人类癌细胞中进行研究后证明能够稳定G-四链体和R环，并显示出与形成微核有关的有效的细胞杀伤活性，基因组不稳定的明显迹象。