5种新型四氢喹啉衍生物的合成及其体外抗肿瘤活性评价

Synthesis and Anti-tumor Activity in vitro of 5 Kinds of New Tetrahydroquinoline Derivatives

目的:设计并合成5种新型的由不同基团取代的吡喃或呋喃并四氢喹啉衍生物,并研究其体外抗肿瘤活性。方法:以对氟硝基苯为原料,经乌尔曼反应、钯碳还原、氮杂-双烯合成反应等方法合成了四氢喹啉8位上分别由2-甲氧基苯基、5-甲基吡啶-2-胺、N-5,5,8,8-四甲基-5,6,7,8-四氢萘-2-胺、N-丙基-N-5,5,8,8-四甲基-5,6,7,8-四氢萘-2-胺、咪唑取代的5种呋喃或吡喃并四氢喹啉衍生物,即目标化合物1、2、3、4、5。采用磺酰罗丹明B比色法,分别考察5种目标化合物对人肝癌细胞HepG2、人白血病细胞Leu02、人肺癌细胞Lu-04的体外抗肿瘤活性。结果:经质谱(MS)及核磁共振(1H-NMR)表征确证成功合成了目标化合物1、2、3、4、5,收率分别为43%、32%、33%、35%、62%。其作用后细胞的生长率分别为HepG2:97.00%、114.52%、96.54%、112.23%、99.70%;Leu02:93.44%、98.95%、70.56%、99.45%、85.93%;Lu-04:104.24%、107.63%、79.96%、104.32%、96.25%。结论:合成了5种新型四氢喹啉衍生物,其中化合物3对Leu02、Lu-04细胞有一定的体外抑制作用。

OBJECTIVE： To design and synthesize 5 kinds of new pyran or furan-tetrahydroquinoline derivatives substituted by different groups, and to research their anti-tumor activities in vitro. METHODS： Using fluoronitrobenzene as raw material, the target compound 1, 2, 3, 4, 5 were synthesized through Ullmann coupling reaction, palladium carbon reduction and aza-Diels-Alder reaction, i.e. pyran or furan-tetrahydroquinoline derivatives substituted by 2-metoxybenzene, 5-picoline-2-amine, N-5, 5,8,8-tetra- methyl-5,6, 7,8-tetralin-2-amine, N-propyl-N-5, 5,8,8-tetramethyl-5,6, 7,8-tetralin-2-amine and imidazole on eighth site. Anti-tu- mor activities of target compound 1, 2, 3, 4, 5 to human hepatic cell HepG2, human leukemia cell Leu02 and human lung cancer cell Lu-04 were investigated by rhodamine B colorimetry respectively. RESULTS： The chemical structure of target compound 1, 2, 3, 4, 5 were characterized by MS and 1H-NMR, with yield of 43%, 32%, 33%, 35% and 62%, respectively. After treatment, the growth rates of HepG2 were 97.00%, 114.52%, 96.54%, 112.23% and 99.70% ; those of Leu02 were 93.44%, 98.95%, 70.56%, 99.45% and 85.93% ; those of Lu-04 were 104.24%, 107.63%, 79.96%, 104.32% and 96.25%, respectively. CON- CLUSIONS： 5 kinds of new tetrahydroquinoline derivatives have been synthesized, and the compound 3 exhibits some anti-tumor activity in vitro to Leu02 and Lu-04.