合成的哌啶并噻吩类化合物抑制肺癌细胞生长的初步研究  

The Preliminary Research of Synthetic Piperidinothieno Compounds Inhibited the Growth of the Lung Cancer Cells

作　　者：韦杰[1] 潘卉[1] 赵扬[1] 冯阳[1] 

机构地区：[1]昆明理工大学生命科学与技术学院,中国云南昆明650500

出　　处：《生命科学研究》2014年第5期382-386,共5页Life Science Research

基　　金：昆明理工大学重点学科项目(14078183);昆明理工大学人才科研启动项目(14118416)

摘　　要：为了发现新的可用于肺癌治疗的小分子药物,从实验室现有的小分子化合物库中,选取13个未见报道的新型哌啶并噻吩类化合物,对其抑制肺癌A549细胞生长的作用进行初步评价。通过体外培养A549细胞,应用WST-1法检测小分子化合物(终浓度为10μmol/L)处理后细胞存活率的变化,发现化合物11(噻吩并[2,3-c]哌啶-3-甲酰胺-2-[(3-甲氧基-萘-2-羰基)-氨基]-6-苄基-,盐酸盐)能显著抑制A549细胞的生长,抑制率可达到(71.34±0.96)%。对小分子化合物结构与活性关系的分析发现苯并结构可能是增强化合物对A549细胞生长的抑制作用的关键结构基团。随后,进一步分析了化合物11(终浓度分别为1、2.5、5、10μmol/L)对A549细胞和正常人胚肺成纤维MRC-5细胞生长的抑制作用。结果表明,随着该化合物浓度增加,对A549细胞生长的抑制率逐渐增大,用GraphPad Prism软件计算出该化合物的IC50为2.407μmol/L;而该化合物对MRC-5细胞生长的抑制率显著低于对A549细胞生长的抑制率,当作用终浓度为10μmol/L时,其对MRC-5细胞生长的抑制率也只有30.41%。这些研究结果初步显示化合物11是一种新的较为理想的治疗肺癌药物先导化合物的候选分子。To discover new effective small molecules for the treatment of lung cancer, 13 new types of piperidinothieno compounds were selected from the small molecule compounds library in our lab, and their biological function on the inhibition of the growth of lung cancer A549 cells was performed. A549 cell viability was detected after small molecules were added （final concentration 10 μmol/L） via WST-1 method. The results showed the compounds 11 （Thieno [2, 3-el piperidine-3-carboxamide-2-[（3-methoxy-naphtha- lene-2-carbonyl）-amino]-6-（benzyl）-, hydrochloride） was the most effective small molecule, with an inhibi- tion ratio of （71.34±0.96）% in A549 cell growth. The analysis of the relationship between structure and activity of small molecule compounds showed that benzene structure maybe a key structure in improving inhibition ratio of small molecules in inhibiting A549 cell growth. Then, the dosage effect of compounds 11 on the growth of A549 cells and the human embryonic lung cells, MRC-5 cell, was analyzed respectively. The results showed that with increased concentration of compounds 11, the viability of A549 cell decreased gradually. The ICso of the compound 11 is 2.407 μmol/L calculated by GraphPad Prism. While, the inhibition ratio of compound 11 in MRC-5 cell growth was 30.41% when the concentration was 10 μmol/L, which significantly lower than that in A549 cell growth. These results showed compound 11 may be a good candi- date of drug lead compound for treatment of lung cancer.

关 键 词：肺癌 A549细胞 MRC-5细胞 细胞生长 哌啶并噻吩 结构活性关系 

分 类 号：Q279[生物学—细胞生物学]