Design and Synthesis of Pyrrolo[2,1-a]Isoquinoline-Based Derivatives as New Cytotoxic Agents

Authors

  • Samaneh Kakhki 1Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2Torbat Heydarieh University of Medical Sciences, Torbat Heydarieh, Iran
  • Sorayya Shahosseini Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract:

A new series of anti-cancer agents based on 1,2-diaryl-5,6-dihydropyrrolo[2,1-a]isoquinoline scaffold containing N,N-diethylamino‌ethoxy, piperidinyl‌ethoxy or morpholinyl‌ethoxy group at the para 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 IC50 values ranging from 1.93 to 33.84 µM.

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Journal title

volume 15  issue 4

pages  743- 751

publication date 2016-11-01

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