Two-carbon tethered artemisinin-isatin hybrids: design, synthesis, anti-breast cancer potential, and in silico study.
Two-carbon tethered artemisinin-isatin hybrids: design, synthesis, anti-breast cancer potential, and in silico study.
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DOI：
10.3389/fmolb.2023.1293763
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发表时间：
2023
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
本文设计、合成了11个两碳链连接的青蒿素-靛红杂合物（4a-k），并对其抗MCF-7、MDA-MB-231和MDA-MB-231/ADR乳腺癌细胞系的增殖活性以及对MCF-10A细胞的细胞毒性进行了评价。其中，代表性的杂合物4a（IC 50：2.49-12.6 μM）对三种测试的乳腺癌细胞系上级青蒿素（IC 50：72.4->100 μM）、双氢青蒿素（IC 50：69.6-89.8 μM）和阿霉素（IC 50：4.46->100 μM）。构效关系研究表明，青蒿素与靛红之间烷基连接基的长度对活性影响很大，因此进一步的结构修饰可以集中在对连接基的评价上。计算机模拟研究用于研究最有前途的杂交体4a的机制。靶点预测、生物信息学、分子对接和分子动力学研究表明，最有希望的杂合物4a可能通过作用于EGFR、PIK 3CA和MAPK 8等多个靶点，从而参与多个肿瘤相关信号通路，发挥抗乳腺癌活性。
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.
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影响因子：
3.7
作者：
Schroeder, Rieke;Illert, Anna-Lena;Erbes, Thalia;Flotho, Christian;Luebbert, Michael;Duque-Afonso, Jesus
通讯作者：
Duque-Afonso, Jesus
影响因子：
--
作者：
Li Y;Rata I;Chiu SW;Jakobsson E
通讯作者：
Jakobsson E
影响因子：
3.9
作者：
Dai, Weibo;Yang, Jing;Liu, Xin;Mei, Quanxi;Peng, Weijie;Hu, Xianjing
通讯作者：
Hu, Xianjing
DOI：
10.1093/database/baq020
发表时间：
2010-08-05
期刊：
Database : the journal of biological databases and curation
影响因子：
--
作者：
Safran M;Dalah I;Alexander J;Rosen N;Iny Stein T;Shmoish M;Nativ N;Bahir I;Doniger T;Krug H;Sirota-Madi A;Olender T;Golan Y;Stelzer G;Harel A;Lancet D
通讯作者：
Lancet D
影响因子：
5.6
作者：
Lau KH;Tan AM;Shi Y
通讯作者：
Shi Y