Zhou Shiyang, Chen Guangying
College of Chemistry and Chemical Engineering, Hainan Normal University Haikou 571158 China
Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, Hainan Normal University Haikou 571158 China.
RSC Adv. 2018 Nov 8;8(66):37643-37651. doi: 10.1039/c8ra08246d. eCollection 2018 Nov 7.
Malignant tumors are a serious threat to human health and are generally treated with chemical therapy. This chemical therapy uses agents that act on signal transduction pathway mechanism of tumor with good selectivity and low toxicity. Sorafenib is a multikinase target inhibitor with good tumor inhibitory activity and a protein kinase inhibitor. In this research, a novel series of sorafenib analogues and derivatives were designed, synthesized, and evaluated as tumor inhibitors. These compounds used sorafenib as the lead compound and achieved modifications using bioisosteres and the alkyl principle. The the results showed that compounds 3c, 3d, 3h, 3n, 3r, and 3z had good inhibitory effects on human cervical cancer cells (Hela), while compounds 3t and 3v had good inhibitory effects on human lung cancer cells (H1975 and A549). Among these, compound 3d had an inhibitory activity (IC) of 0.56 ± 0.04 μmol L against Hela cells (human cervical cancer), the compound 3t had an IC of 2.34 ± 0.07 μmol L against H1975 cells (human lung cancer), and compound 3v had an IC of 1.35 ± 0.03 μmol L against A549 cells (human lung cancer). The results showed that these compounds had good antitumor effects and low acute toxicity.
恶性肿瘤对人类健康构成严重威胁，通常采用化学疗法进行治疗。这种化学疗法使用的药物对肿瘤的信号转导通路机制具有良好的选择性且毒性较低。索拉非尼是一种具有良好肿瘤抑制活性的多激酶靶点抑制剂，也是一种蛋白激酶抑制剂。在本研究中，设计、合成并评估了一系列新型索拉非尼类似物和衍生物作为肿瘤抑制剂。这些化合物以索拉非尼为先导化合物，利用生物电子等排体和烷基原理进行修饰。结果表明，化合物3c、3d、3h、3n、3r和3z对人宫颈癌细胞（Hela）具有良好的抑制作用，而化合物3t和3v对人肺癌细胞（H1975和A549）具有良好的抑制作用。其中，化合物3d对Hela细胞（人宫颈癌）的抑制活性（IC）为0.56±0.04μmol/L，化合物3t对H1975细胞（人肺癌）的IC为2.34±0.07μmol/L，化合物3v对A549细胞（人肺癌）的IC为1.35±0.03μmol/L。结果表明，这些化合物具有良好的抗肿瘤作用且急性毒性较低。
