School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China; Key Laboratory of Theoretical Organic Chemistry and Function Molecule of Ministry of Education, Hunan University of Science and Technology, Xiangtan 411201, China; Hunan Provincal Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, Xiangtan 411201, China.
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China.
Eur J Med Chem. 2018 Feb 10;145:35-40. doi: 10.1016/j.ejmech.2017.12.038. Epub 2017 Dec 15.
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 NMR, C NMR, and HRMS. All the newly prepared compounds (3a-3m) were in vitro evaluated 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 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 IC values of 8.17 μM and 3.15 μM against HCT116 and MGC803 cell lines, respectively, which was 1.4-8.1 times more potent than 5-Fluorouracil (IC = 11.29 μM and 25.54 μM 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.
采用杂合药效团方法设计和合成了一系列新型的吡啶酮-噻唑杂合化合物。通过 IR、H NMR、C NMR 和 HRMS 确定了化合物的结构。所有新制备的化合物（3a-3m）均在体外对三种人癌细胞系（结肠癌细胞系（HCT-116）、胃癌细胞系（MGC803）和肝癌细胞系（Huh7））进行了抗增殖活性评估。生物测定结果表明，大多数测试化合物对各种癌细胞具有很强的体外抗肿瘤活性，一些化合物的作用比阳性对照 5-氟尿嘧啶（5-FU）更强。化合物 3b 对 HCT116 和 MGC803 细胞系的 IC 值分别为 8.17 μM 和 3.15 μM，显示出最佳的抗肿瘤活性，比 5-氟尿嘧啶（IC = 11.29 μM 和 25.54 μM 对 HCT116 和 MGC803）分别强 1.4-8.1 倍。这些发现表明，化合物 3b 可能具有开发为新型抗癌小分子药物的有前途的先导物的潜力。
