含酰胺结构的新型2-氨基-4-苯基噻唑类化合物的合成及抗癌和抗菌活性研究
收稿日期: 2017-04-13
修回日期: 2017-04-23
网络出版日期: 2017-05-04
Synthesis, Anticancer and Antibacterial Activities of Novel 2-Amino-4-phenylthiazole Derivatives Containing Amide Moiety
Received date: 2017-04-13
Revised date: 2017-04-23
Online published: 2017-05-04
基于索拉非尼的结构特征设计、合成了一系列含有酰胺结构的新型2-氨基-4-苯基噻唑类化合物.所合成的化合物结构经1H NMR，13C NMR和HRMS表征，并对目标化合物的抗肿瘤和抗菌活性进行了研究.体外抗肿瘤抑制活性结果表明，部分目标化合物显示出较好的活性，特别是N-[3-（2-乙酰氨基噻唑-4-基）苯基]-3-氟苯甲酰胺（4n）对人类结肠癌细胞（HT29）和人肺上皮细胞（A549）细胞株具有显著的抗肿瘤作用，IC50值分别为6.31和7.98 μmol·L-1.进一步的研究表明化合物4n可以影响Raf/MEK/ERK信号通路.此外，体外抗菌活性筛选发现，N-[3-（2-乙酰氨基噻唑-4-基）苯基]-3，4-二氯苯甲酰胺（4h）、N-[3-（2-乙酰氨基噻唑-4-基）苯基]-3-氯苯甲酰胺（4i）和N-[3-（2-乙酰氨基噻唑-4-基）苯基]-2，4-二氯苯甲酰胺（4o）对革兰氏阳性菌、革兰氏阴性菌均具有较好抑制作用.
张志华 , 陈羽 , 柴宝山 , 杨小漫 , 蔡晓瑜 , 崔博 , 游松 . 含酰胺结构的新型2-氨基-4-苯基噻唑类化合物的合成及抗癌和抗菌活性研究[J]. 有机化学, 2017 , 37(9) : 2377 -2384 . DOI: 10.6023/cjoc201704023
A series of novel 2-amino-4-phenylthiazole derivatives containing amide moiety were designed and synthesized based on the structural features of sorafenib. The structures of synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS. Both the anticancer and antibacterial activities of all the target compounds were evaluated. Most of the compounds showed potent activities, especially N-(3-(2-acetamidothiazol-4-yl)phenyl)-3-fluorobenzamide (4n) exhibited a remarkable antitumor effect against human colon cancer cell line (HT29) and human lung epithelial cells (A549) cells with IC50 values of 6.31 and 7.98 μmol·L-1, respectively. Further mechanistic study revealed that 4n can influence the Raf/MEK/ERK pathway. In addition, N-(3-(2-acetamidothiazol-4-yl)phenyl)-3,4-dichlorobenzamide (4h), N-(3-(2-acetamidothiazol-4-yl)phenyl)-3-chlorobenzamide (4i) and N-(3-(2-acetamidothiazol-4-yl)phenyl)-2,4-dichlorobenzamide (4o) exhibit moderate antibacterial activity against the tested bacteria.
Key words： thiazole derivative; amide; synthesis; anticancer; antibacterial
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