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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7.98μmol·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.
Based on the structural characteristics of sorafenib, a series of novel 2-amino-4-phenylthiazoles containing amide structures were synthesized.The structures of the synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS, and the target compounds Antitumor activity and antimicrobial activity were studied in vitro.Results of antitumor activity in vitro showed that some of the target compounds showed good activity, especially N- [3- (2-acetamidothiazol-4-yl) phenyl] - 3-Fluorobenzamide (4n) has a significant anti-tumor effect on human colon cancer cell line (HT29) and human lung epithelial cell line (A549) with IC50 values of 6.31 and 7.98 μmol·L -1, respectively.Further studies Indicating that compound 4n can affect the Raf / MEK / ERK signaling pathway.In addition, in vitro antibacterial activity screening found that N- [3- (2-acetamidothiazol-4-yl) phenyl] -3,4-dichlorobenzamide (4h) and N- [3- (2-acetamidothiazol-4-yl) phenyl] -3- chlorobenzamide (4i) Phenyl] -2,4-dichlorobenzamide (4o) against Gram-positive bacteria, Gram-negative bacteria have a good inhibitory effect.