Design, synthesis and biological evaluations of novel pyridone-thiazole hybrid molecules as antitumor agents.
Design, synthesis and biological evaluations of novel pyridone-thiazole hybrid molecules as antitumor agents.
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DOI：
10.1016/j.ejmech.2017.12.038
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发表时间：
2018-02
影响因子：
6.7
通讯作者：
Wenlin Xie;Yiqiang Wu;Jingai Zhang;Qihong Mei;Yahan Zhang;Ning Zhu;Renzhi Liu;Huilin Zhang
中科院分区：
文献类型：
--
作者：
Wenlin Xie;Yiqiang Wu;Jingai Zhang;Qihong Mei;Yahan Zhang;Ning Zhu;Renzhi Liu;Huilin Zhang
采用杂化药效团方法设计合成了一系列新的吡啶酮-噻唑杂化化合物。化合物的结构经红外光谱、核磁共振氢谱、核磁共振碳谱和高分辨质谱学确证。所有新合成的化合物(3a-3m)在体外对结肠癌(HCT-116)、胃癌(MGC803)和肝细胞癌(HuH7)三种人癌细胞株的增殖抑制活性进行了评价。生物活性测定结果表明，大部分受试化合物在体外对多种肿瘤细胞具有较强的抗肿瘤活性，部分化合物的抗肿瘤活性强于阳性对照5-氟尿嘧啶(5-FU)。化合物3b对HCT116和MGC803 细胞的IC50值分别为8.17μM和3.15μM，是5-氟尿嘧啶的1.4~8.1倍(对HCT116和MGC803的IC50值分别为11.29和25.54μM)。这些发现表明，化合物3b可能被开发为设计新型抗癌小分子药物的有前途的先导化合物。
A hybrid pharmacophore approach was adopted to design and synthesize new series of pyridone-thiazole hybrid compounds. The structures of the compounds were established by IR,1H NMR,13C NMR, and HRMS. All the newly prepared compounds (3a-3m) werein vitroevaluated for their antiproliferative activity against three human cancer cell lines, namely Colon cancer (HCT-116), gastric carcinoma (MGC803) and hepatocellular cancer (Huh7). Bioassay results demonstrated that most of the tested compounds showed potent anti-tumor activities against various cancer cellsin vitro, and some compounds exhibited stronger effects than positive control 5-Fluorouracil (5-FU). Compound3bshowed the best anti-tumor activity with IC50values of 8.17μM and 3.15μM against HCT116 and MGC803 cell lines, respectively, which was 1.4–8.1 times more potent than 5-Fluorouracil (IC50= 11.29μM and 25.54μM against HCT116 and MGC803 respectively). These findings suggest that compound3bmay have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.