Synthesis and cytotoxic activity of novel 3-methyl-1-[(4-substitutedpiperazin-1-yl)methyl]-1 H-indole derivatives

Date
2012
Authors
Koksal, M.
Yarim, M.
Durmaz, I.
Cetin Atalay, R.
Advisor
Supervisor
Co-Advisor
Co-Supervisor
Instructor
Source Title
Arzneimittel-Forschung/Drug Research
Print ISSN
0004-4172
Electronic ISSN
Publisher
Thieme
Volume
62
Issue
8
Pages
389 - 394
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
Series
Abstract

A series of novel 3-methyl-1-[(4-substitutedpiperazin-1-yl)methyl]-1H- indoles (3a-l) were synthesized and their cytotoxicities were analyzed against 3 different human cell lines, including liver (HUH7), breast (MCF7) and colon (HCT116). The Mannich reaction of 3-methylindole (1) with 4- substitutedpiperazines (2) and formaldehyde resulted to the 3-methyl-1-[(4- substitutedpiperazin-1-yl)methyl]-1H-indoles (3a-l) in 38-69% yields. The investigation of anticancer screening revealed that the tested compounds showed comparable activity to the reference drug 5-fluorouracil and compounds 3g, 3h, 3i and 3k, had lower 50% inhibition (IC 50) concentration than reference drug. Moreover, the cytotoxic effect of the most potent compound 3h on HUH7 and MCF7 cells through apoptosis was visualized by Hoechst staining and compared with paclitaxel, which is a mitotic inhibitor acting on microtubules. The morphological features of apoptosis were observed as condensed and fragmented nuclei that are similar to paclitaxel. © Georg Thieme Verlag KG Stuttgart.New York.

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Book Title
Keywords
Anticancer, Apoptosis, Indole, Mannich base
Citation
Published Version (Please cite this version)