Design, synthesis and biological evaluation of novel 2,4-bismorpholinothieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives as potent antitumor agents.,Bioorganic Chemistry

当前位置： X-MOL 学术 › Bioorgan. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Design, synthesis and biological evaluation of novel 2,4-bismorpholinothieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives as potent antitumor agents.
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2020-03-31 , DOI: 10.1016/j.bioorg.2020.103796
Tianyu Ye ₁ , Yufei Han ₁ , Ruxin Wang ₁ , Pingzhen Yan ₁ , Shaowei Chen ₁ , Yunlei Hou ₁ , Yanfang Zhao ₁

Affiliation

To develop novel therapeutic agents with anticancer activities, two series of novel 2,4-bismorpholinyl-thieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives were designed, synthesized and evaluated for their biological activities. Among them, compound A12 showed the most potent antitumor activities against HCT116, PC-3, MCF-7, A549 and MDA-MB-231 cell lines with IC50 values of 3.24 μM, 14.37 μM, 7.39 μM, 7.10 μM, and 16.85 μM, respectively. Further explorations in bioactivity were conducted to clarify the anticancer mechanism of compound A12. The results showed that compound A12 obviously inhibited the proliferation of A549 cell lines and decreased mitochondrial membrane potential, which led to the apoptosis of cancer cells and suppressed the migration of tumor cells.

中文翻译：

新型2,4-双吗啉代噻吩并[3,2-d]嘧啶和2-吗啉代噻吩并[3,2-d]嘧啶酮衍生物的设计，合成及生物学评价为有效的抗肿瘤药。

为了开发具有抗癌活性的新型治疗药物，设计，合成和评估了两个系列的新型2,4-双吗啉基-噻吩并[3,2-d]嘧啶和2-吗啉代噻吩并[3,2-d]嘧啶酮衍生物。活动。其中，化合物A12对HCT116，PC-3，MCF-7，A549和MDA-MB-231细胞系表现出最强的抗肿瘤活性，IC50值分别为3.24μM，14.37μM，7.39μM，7.10μM和16.85μM ，分别。进行了进一步的生物活性探索，以阐明化合物A12的抗癌机制。结果表明，化合物A12明显抑制A549细胞株增殖，降低线粒体膜电位，导致癌细胞凋亡，抑制肿瘤细胞迁移。

更新日期：2020-04-20

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11