title: New, Substituted Derivatives of Dicarboximides and their Cytotoxic Properties.
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.
authors.forename: Bożena
authors.initials: B
authors.lastname: Kuran
authors.affiliation: Postal Address: Chair and Department of Biochemistry, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland. mariola.krawiecka@wum.edu.pl.
authors.forename: Mariola
authors.initials: M
authors.lastname: Napiórkowska
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kossakowski
authors.affiliation: Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 112 Sienkiewicza Str., 90-363 Lodz, Poland. marcin@cbmm.lodz.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Cieślak
authors.forename: Julia
authors.initials: J
authors.lastname: Kaźmierczak-Barańska
authors.forename: Karolina
authors.initials: K
authors.lastname: Królewska
authors.forename: Barbara
authors.initials: B
authors.lastname: Nawrot
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D007094:Imides / Q000737:chemistry / Q000494:pharmacology*; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D007094:Imides