Design, synthesis and biological evaluations of novel pyridone-thiazole hybrid molecules as antitumor agents

作者：Xie, Wenlin^*; Wu, Yiqiang; Zhang, Jingai; Mei, Qihong; Zhang, Yahan; Zhu, Ning; Liu, Renzhi; Zhang, Huilin

来源：European Journal of Medicinal Chemistry, 2018, 145: 35-40.

DOI：10.1016/j.ejmech.2017.12.038

• Pyridone
• Thiazole
• Hybrids
• Synthesis
• Antitumor activity

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, H-1 NMR, C-13 NMR, and HRMS. All the newly prepared compounds (3a-3m) were in vitro evaluated for their anti proliferative 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 cells in vitro, and some compounds exhibited stronger effects than positive control 5-Fluorouracil (5-FU). Compound 3b showed the best anti-tumor activity with IC50 values of 8.17 mu M and 3.15 mu M against HCT116 and MGC803 cell lines, respectively, which was 1.4-8.1 times more potent than 5-Fluorouracil (IC50 = 11.29 mu M and 25.54 mu M against HCT116 and MGC803 respectively). These findings suggest that compound 3b may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.

• 出版日期2018-2-10
• 单位湖南科技大学