设计、合成了 11 种二碳栓系青蒿素-靛红杂合体 (4a-k)，并评估了它们对 MCF-7、MDA-MB-231 和 MDA-MB-231/ADR 乳腺癌细胞系的抗增殖活性，如下：以及本文对MCF-10A细胞的细胞毒性。其中，代表性杂交4a（IC50：2.49-12.6 µM）优于青蒿素（IC50：72.4->100 µM）、二氢青蒿素（IC50：69.6-89.8 µM）和阿霉素（IC50：4.46->100 µM）针对三种测试的乳腺癌细胞系。构效关系表明，青蒿素和靛红之间的烷基连接体的长度对于活性至关重要，因此进一步的结构修饰可以集中在连接体的评估上。计算机模拟研究用于研究最有前途的混合 4a 的机制。靶点预测、生物信息学、分子对接和分子动力学揭示，最有前途的杂交4a可能通过作用于EGFR、PIK3CA和MAPK8等多个靶点，从而参与多个肿瘤相关信号通路来发挥抗乳腺癌活性。 © 2023 王、黄、袁、王、沉。

Eleven two-carbon tethered artemisinin-isatin hybrids (4a-k) were designed, synthesized, and evaluated for their antiproliferative activity against MCF-7, MDA-MB-231, and MDA-MB-231/ADR breast cancer cell lines, as well as cytotoxicity toward MCF-10A cells in this paper. Among them, the representative hybrid 4a (IC50: 2.49-12.6 µM) was superior to artemisinin (IC50: 72.4->100 µM), dihydroartemisinin (IC50: 69.6-89.8 µM), and Adriamycin (IC50: 4.46->100 µM) against the three tested breast cancer cell lines. The structure-activity relationship revealed that the length of the alkyl linker between artemisinin and isatin was critical for the activity, so further structural modification could focus on evaluation of the linker. The in silico studies were used to investigate the mechanism of the most promising hybrid 4a. Target prediction, bioinformatics, molecular docking, and molecular dynamics revealed that the most promising hybrid 4a may exert anti-breast cancer activity by acting on multiple targets such as EGFR, PIK3CA, and MAPK8 and thus participating in multiple tumor-related signaling pathways.Copyright © 2023 Wang, Huang, Yuan, Wang and Shen.