Kakhki Samaneh, Shahosseini Soraya, Zarghi Afshin
Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti Universityof Medical Sciences, Tehran, Iran. ; Torbat Heydarieh University of Medical Sciences, Torbat Heydarieh, Iran.
Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran .
Iran J Pharm Res. 2016 Fall;15(4):743-751.
A new series of anti-cancer agents based on 1,2-diaryl-5,6-dihydropyrrolo[2,1-a]isoquinoline scaffold containing N,N-diethylamino-ethoxy, piperidinyl-ethoxy or morpholinyl-ethoxy group at the position of the C-2 phenyl ring were synthesized and their cytotoxic activities were assessed against several human cancer cell lines including MCF-7 (ER positive breast cancer cell), MDA-MB231 (ER-negative breast cancer cell), T47D (Human ductal breast epithelial tumor cell line), A549 (adenocarcinomic human alveolar basal epithelial cells), and Hela (human cervix adenocarcinoma cells) using MTT assay. Based on results, compounds, 1-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-5,6-dihydro-8,9-dimethoxy-2-phenylpyrrolo[2,1-a]isoquinoline (6a) and 2-(4-(5,6-dihydro-8,9-dimethoxy-2-phenylpyrrolo[2,1-a] isoquinolin-1-yl)phenoxy)-N,N-diethylethanamine (6c) were the most potent cytotoxic compounds and more toxic than the reference compound against T47D cell line, while all the compounds had satisfactory activity against HeLa cell line with mean IC values ranging from 1.93 to 33.84 µM.
合成了一系列基于1,2-二芳基-5,6-二氢吡咯并[2,1-a]异喹啉骨架的新型抗癌剂，这些化合物在C-2苯环的位置含有N,N-二乙氨基乙氧基、哌啶基乙氧基或吗啉基乙氧基，并使用MTT法评估了它们对几种人类癌细胞系的细胞毒性活性，这些细胞系包括MCF-7（雌激素受体阳性乳腺癌细胞）、MDA-MB231（雌激素受体阴性乳腺癌细胞）、T47D（人乳腺导管上皮肿瘤细胞系）、A549（人肺泡基底上皮腺癌细胞）和Hela（人宫颈腺癌细胞）。根据结果，化合物1-(4-(2-(哌啶-1-基)乙氧基)phenyl)-5,6-二氢-8,9-二甲氧基-2-苯基吡咯并[2,1-a]异喹啉（6a）和2-(4-(（5,6-二氢-8,9-二甲氧基-2-苯基吡咯并[2,1-a]异喹啉-1-基）苯氧基)-N,N-二乙胺（6c）是最有效的细胞毒性化合物，并且对T47D细胞系的毒性比参考化合物更大，而所有化合物对Hela细胞系都具有令人满意的活性，平均IC值范围为1.93至33.84μM。
