作为生物医学领域的科学家，您精通英语和简化汉语。将以下段落准确地翻译为简化的汉语，符合学术论文的语言模式，并保持原始陈述的结构： 设计、合成、生物评价、激酶选择性和体外计算结果的新型4-(2-芳基亚烯酰基肼基)噻吩嘧啶衍生物作为抗癌EGFR抑制剂。
Novel 4-(2-arylidenehydrazineyl)thienopyrimidine derivatives as anticancer EGFR inhibitors: Design, synthesis, biological evaluation, kinome selectivity and in silico insights.
发表日期：2023 Aug 22
作者：
Heba A Elsebaie, Eman A El-Bastawissy, Kamel M Elberembally, Eman F Khaleel, Rehab Mustafa Badi, Moataz A Shaldam, Wagdy M Eldehna, Haytham O Tawfik, Tarek F El-Moselhy
来源：
BIOORGANIC CHEMISTRY
摘要：
当前研究发现了15个具有潜在抗癌作用的新的噻唑[2,3-d]嘧啶衍生物，包括5a-l、6和7a-b。NCI筛选结果表明，化合物5f-i和7a在MDA-MB-468细胞的平均GI%和GI50水平上显著抑制了增殖。与阿霉素相比，这些化合物（5f-i和7a）对于典型的WI-38细胞表现出更好的安全性。当抑制EGFR激酶时，化合物5g和7a与厄洛替尼相比具有最高的抑制作用（两位数的纳摩尔）。基于上述结果，对5g的能够干扰细胞周期并在乳腺癌MDA-MB-468细胞株中诱导凋亡的能力进行了检测。检测到了凋亡标记物Bax、Bcl-2、Caspase-8和Caspase-9。采用分子对接和动力学模拟的方法解释了最具活性化合物的生物活性。 版权© 2023 Elsevier Inc. 保留所有权利。
The current study discovered fifteen new thieno[2,3-d]pyrimidine derivatives with potential anticancer action, including 5a-l, 6, and 7a-b. Results from the NCI screening revealed that compounds 5f-i and 7a significantly inhibited the proliferation of MDA-MB-468 cells at mean GI% and GI50 levels. Compared to staurosporine, these compounds (5f-i and 7a) demonstrated better safety towards typical WI-38 cells. Compounds 5g and 7a demonstrated the highest inhibition (two-digit nanomolar) when compared to erlotinib when their potency was tested on EGFR kinase. Considering the outcomes above, 5g was examined for its ability to disrupt the cell cycle with trigger apoptosis in breast cancer MDA-MB-468 cell lines. The apoptosis markers Bax, Bcl-2, Caspase-8, and Caspase-9, were detected. In silico molecular docking and dynamic simulation were used to explainthe biological activities of the most potent compound.Copyright © 2023 Elsevier Inc. All rights reserved.