We previously reported a series of p53-elevating anthraquinone compounds with considerable cytotoxicity for acute lymphoblastic leukemia (ALL) cells. To further develop this class of compounds, we examined the effect of a few key structural features on the anticancer structure–activity relationship (SAR) in ALL cells. The active analogs showed comparable cytotoxicity and upregulation of p53 but did not induce significant downregulation of MDM2 as seen with the lead compound AQ-101, indicating the importance of the anthraquinone core scaffold for MDM2 regulation. The result from the current study not only contributes to the SAR framework of these anthraquinone derivatives but also opens up new chemical space for further optimization work.

中文翻译：

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通过上调p53诱导细胞凋亡：蒽醌类似物的结构活性探索。

我们以前报道了一系列p53升高的蒽醌化合物，对急性淋巴细胞白血病（ALL）细胞具有相当大的细胞毒性。为了进一步开发此类化合物，我们研究了一些关键结构特征对ALL细胞中抗癌结构-活性关系（SAR）的影响。活性类似物显示出可比的细胞毒性和p53的上调，但没有诱导MDM2的显着下调（如先导化合物AQ-101所示），表明蒽醌核心支架对于MDM2调节的重要性。当前研究的结果不仅有助于这些蒽醌衍生物的SAR构架，而且还为进一步优化工作开辟了新的化学空间。