New, Substituted Derivatives of Dicarboximides and their Cytotoxic Properties

Author(s):

Bożena Kuran, Mariola Napiórkowska, Jerzy Kossakowski, Marcin Cieślak, Julia Kaźmierczak-Barańska, Karolina Królewska and Barbara Nawrot   Pages 852 - 864 ( 13 )

Abstract:

A large group of aminoalkyl and aminoalkanol derivatives of selected dicarboximides were synthesized and characterized by 1HNMR, 13CNMR and ESI MS spectra analysis. The thirty nine new compounds were tested for their cytotoxic properties in human chronic (K562), acute leukemia (HL-60), and cervical cancer cells (HeLa) as well as in normal endothelial cells (HUVEC). The most promising compounds are 4-[2-(dimethylamino)ethyl]-, (diethylamino) ethyl]-, 4-[2-(piperidin-1-yl)ethyl]-, 4-[3-(dimethylamino)propyl]- and 4-[2-hydroxy-3-(propan- 2-ylamino)propyl]- derivatives of 1,7-diethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0^2,6]dec-8-ene-3,5,10-trione exhibiting high and selective cytotoxicity towards K562 and HL-60 cells (IC₅₀ in the range of 1-10 µM) while being non-toxic towards HUVEC and HeLa cells (IC₅₀> 100 μM). Moreover, the preliminary studies have showed that 4-[2-(piperidin-1-yl)ethyl]- 1,7-diethyl-8,9-diphenyl-4-azatricyclo [5.2.1.0^2,6]dec-8-ene-3,5,10-trione induces programmed cell death (apoptosis) in leukemia cells.

Keywords:

Dicarboximides, cytotoxic properties, HeLa, HL-60, K562, apoptosis.

Affiliation:

, Postal Address: Chair and Department of Biochemistry, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland., , Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 112 Sienkiewicza Str., 90-363 Lodz, Poland.

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