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以二苯乙酸和4,4-二(4-氟苯)氯丁烷为原料,经过一系列偶联反应得到系列芳香烷胺类化合物(Ⅰ~Ⅶ),化合物的结构经~1HNMR,~(13)CNMR,MS确证。以化合物Ⅰ为例,对催化剂种类和用量,以及反应温度进行了优化。最佳合成条件为:4-二甲氨基吡啶(DMAP)为催化剂,n(DMAP)∶n[(S)-1-苯乙胺(3a)]=2∶1,反应温度为室温,在此条件下,化合物Ⅰ的收率为86.8%。采用MTT法选用人类前列腺癌细胞(DU145、PC3),乳腺癌细胞(MCF-7、MDB-MB-231、MDB-MB-453)和正常上皮细胞株(926)进行体外抗肿瘤活性测试。体外生物活性评价结果显示,化合物Ⅲ和Ⅳ具有良好的抗肿瘤生物活性,其中,化合物Ⅲ对MDB-MB-231,化合物Ⅳ对MDB-MB-453的抗肿瘤活性最佳[IC_(50)(半抑制浓度)分别为17.38,19.07μmol/L],但二者对正常上皮细胞杀伤效力较大(IC_(50)分别为19.20,26.37μmol/L)。化合物Ⅶ有一定的抗乳腺癌作用(对MCF-7、MDB-MB-231、MDB-MB-453的IC_(50)分别为52.03,49.74,30.09μmol/L),且对正常上皮细胞的IC_(50)>50μmol/L。
A series of aromatic alkyl amines (Ⅰ ~ Ⅶ) were obtained from diphenylacetic acid and 4,4-bis (4-fluorophenyl) chlorobutane through a series of coupling reactions. The structures of the compounds were characterized by ~ 1HNMR, 13) CNMR, MS confirms. Taking compound Ⅰ as an example, the type and amount of catalyst and the reaction temperature were optimized. The optimum synthesis conditions are as follows: 4-dimethylaminopyridine (DMAP) as catalyst, n (DMAP): n [(S) -1-phenylethylamine (3a)] = 2:1, the reaction temperature is room temperature, The yield of compound I was 86.8%. The antitumor activity of human prostate cancer cells (DU145, PC3), breast cancer cells (MCF-7, MDB-MB-231 and MDB-MB-453) and normal epithelial cell line (926) were tested by MTT assay. The results of in vitro bioassay showed that compounds Ⅲ and Ⅳ have good antitumor activity. Among them, compound Ⅲ has the best antitumor activity against MDB-MB-231 and compound IV against MDB-MB-453 [IC 50 ( Half inhibitory concentration) were 17.38 and 19.07μmol / L, respectively, but the killing effect on normal epithelial cells was relatively high (IC 50, 19.20 and 26.37μmol / L, respectively). Compound Ⅶ had certain anti-breast cancer effects (IC 50 of MCF-7, MDB-MB-231 and MDB-MB-453 were 52.03, 49.74 and 30.09 μmol / L, respectively) (50)> 50 μmol / L.