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Design, synthesis, and biological evaluation of novel benzo[b]thiophene-diaryl urea derivatives as potential anticancer agents
Medicinal Chemistry Research ( IF 2.6 ) Pub Date : 2020-05-19 , DOI: 10.1007/s00044-020-02559-8
Omid Zarei , Fereshteh Azimian , Maryam Hamzeh-Mivehroud , Javid Shahbazi Mojarrad , Salar Hemmati , Siavoush Dastmalchi

A hybrid pharmacophore approach was applied to design and synthesize a series of benzo[b]thiophene-diaryl urea derivatives 17a–g with potential anticancer effect. In vitro antiproliferative activities of all target compounds were evaluated against HT-29 and A549 cancer cell lines. Three compounds 17b, 17d, and 17f exhibited antiproliferative activities on both cell lines comparable to that of the positive reference drug sorafenib. Notably, compound 17d demonstrated the highest activity with IC50 values of 5.91 and 14.64 μM on HT-29 and A549 cells, respectively. It also induced apoptosis and cell cycle arrest at the G0/G1 phase on HT-29 cells based on DAPI staining and propidium iodide (PI) staining followed by flow cytometry analyses. Molecular docking studies revealed that 17d can bind well to the active site of VEGFR2 receptor. Collectively, compound 17d can be considered as a promising scaffold amenable for further optimization towards the development of new anticancer agents.

中文翻译:

新型苯并[b]噻吩-二芳基脲衍生物作为潜在抗癌药的设计,合成及生物学评价

一种杂种药效团方法被用于设计和合成一系列具有潜在抗癌作用的苯并[b]噻吩-二芳基脲衍生物17a-g。评估了所有目标化合物对HT-29和A549癌细胞的体外抗增殖活性。三种化合物17b17d17f在两种细胞系中均显示出与阳性参考药物索拉非尼相当的抗增殖活性。值得注意的是,化合物17d的IC 50活性最高在HT-29和A549细胞上的分别值为5.91和14.64μM。基于DAPI染色和碘化丙啶(PI)染色,然后流式细胞仪分析,它还诱导HT-29细胞的G0 / G1期凋亡和细胞周期停滞。分子对接研究表明17d可以很好地结合VEGFR2受体的活性位点。总的来说,化合物17d可以被认为是有前途的支架,适合进一步优化开发新的抗癌剂。
更新日期:2020-05-19
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