The endoperoxide group of artemisinins is a universally accepted essential group for their anti‐cancer effects. In this work, a series of D‐ring‐contracted artemisinin derivatives were constructed by combining ring‐contracted artemisinin core with the fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty‐six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H NMR and 13C NMR data. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to positive controls Palbociclib, with GI50 values of 4.87±0.23 μM and 9.97±1.44 μM towards T47D cells and MDA‐MB‐436 cells respectively. In addition, the results showed that B01 were the most potent compounds against CDK6/cyclin D3 kinase, with IC50 values of 0.135±0.041 μM, its activity is about 1/3 of the positive control Palbociclib.

中文翻译：

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作为新型 CDK4/6 抑制剂的环缩青蒿素衍生物：合成和抗乳腺癌评价

青蒿素的内过氧化物基团因其抗癌作用而被普遍接受。在这项工作中，通过将缩环青蒿素核心与功能性杂环分子或经典CDK4/6抑制剂的片段相结合，构建了一系列D环收缩青蒿素衍生物，以鉴定更有效的乳腺癌治疗药物。合成了 26 种新型杂化分子，并通过 HRMS、IR、1H NMR 和 13C NMR 数据进行了表征。在抗增殖活性和激酶抑制作用测定中，我们发现B01的抗增殖作用与阳性对照Palbociclib接近，对T47D细胞和MDA-MB-436细胞的GI50值分别为4.87±0.23 μM和9.97±1.44 μM。此外，结果显示B01是对抗CDK6/cyclin D3激酶最有效的化合物，IC50值为0.135±0.041 μM，其活性约为阳性对照Palbociclib的1/3。