Anti-proliferative and chemosensitizing effects of diarylheptanoids on human tumor cell lines
Anti-proliferative and chemosensitizing effects of diarylheptanoids on human tumor cell lines
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二芳基庚烷类化合物对人肿瘤细胞系的抗增殖和化疗增敏作用
DOI：
10.1021/acsomega.8b03215
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发表时间：
2019
期刊：
影响因子：
4.1
通讯作者：
Nakagawa-Goto K
中科院分区：
文献类型：
--
作者：
Miyagishi S;Saito Y;Goto M;Nakagawa-Goto K
我们设计合成了5个对称的和16个不对称的二芳基庚烷类化合物，并评价了它们对三阴性乳腺癌和多药耐药(MDR)癌症等顽固性癌症的化学增敏和抗增殖活性。在合成的衍生物中，化合物3对阿霉素和紫杉醇都是最好的候选药物，它们分别以剂量依赖的方式将细胞阻滞在S/G2/M和G2/M期，可能导致细胞周期停滞在G1期。此外，在三阴性乳腺癌细胞(MDA-MB-231)中，在G2/M期略有积累的13与阿霉素共同作用，有效地增强了抗增殖活性。另一方面，具有3，5-二烷基-4-羟基苯基的化合物2，12和14对所有被测试的肿瘤细胞株，包括mdr亚系，显示出强大的抗增殖活性，IC50值为5.08.5μM。
We designed and synthesized 5 symmetric and 16 asymmetric diarylheptanoid derivatives and evaluated their chemosensitizing and antiproliferative activities for intractable cancers such as triple-negative breast and multidrug-resistant (MDR) cancers. Among the synthesized derivatives, compound3, which potentially induced cell cycle arrest at G1, was the best candidate for both doxorubicin and paclitaxel in MDR tumor cells, arresting the cells dose-dependently at S/G2/M and G2/M, respectively. Furthermore, the cotreatment of13, which slightly accumulated at the G2/M phase, with doxorubicin in triple-negative breast cancer cells (MDA-MB-231) effectively enhanced the efficacy of antiproliferative activity. On the other hand, compounds2,12, and14having the 3,5-dialkyl-4-hydroxyphenyl moiety exhibited a potent antiproliferative activity against all tested tumor cell lines, including an MDR subline, with IC50values of 5.0–8.5 μM.