Shandong Provincial Third Hospital, Shandong University, Jinan 250031, China.
State Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology, Jinan 250353, China.
Molecules. 2022 Nov 18;27(22):7994. doi: 10.3390/molecules27227994.
Sixteen dihydroartemisinin-5-methylisatin hybrids and tethered via different carbon spacers were assessed for their antiproliferative activity against MCF-7, MDA-MB-231, MCF-7/ADR and MDA-MB-231/ADR breast cancer cell lines as well as cytotoxicity towards MCF-10A cells to investigate the influence of the length of carbon spacers on the activity. The preliminary results illustrated that the length of the carbon spacer was the main parameter which affected the activity, and hybrids tethered via the two-carbon linker showed the highest activity. Amongst the synthesized hybrids, the representative hybrid (IC: 15.3-20.1 µM) not only demonstrated profound activity against both drug-sensitive and drug-resistant breast cancer cell lines, but also possessed excellent safety and selectivity profile. Collectivity, hybrid was a promising candidate for the treatment of both drug-sensitive and drug-resistant breast cancers and worthy of further preclinical evaluations.
十六个双氢青蒿素-5-甲基靛红杂合体通过不同的碳连接子连接，并评估其对 MCF-7、MDA-MB-231、MCF-7/ADR 和 MDA-MB-231/ADR 乳腺癌细胞系的增殖活性以及对 MCF-10A 细胞的细胞毒性，以研究碳连接子长度对活性的影响。初步结果表明，碳连接子的长度是影响活性的主要参数，通过双碳连接子连接的杂合体表现出最高的活性。在所合成的杂合体中，代表性的杂合体（IC：15.3-20.1 μM）不仅对敏感和耐药的乳腺癌细胞系表现出显著的活性，而且具有良好的安全性和选择性特征。总之，杂合体是一种有前途的治疗敏感和耐药乳腺癌的候选药物，值得进一步进行临床前评估。
