Design, synthesis and cytotoxic evaluation of 4-methylidenepyrazolidin-3-ones

作者：Modranka Jakub; Jakubowski Rafal; Rozalski Marek; Krajewska Urszula; Janecka Anna; Gach Katarzyna; Pomorska Dorota; Janecki Tomasz^*

来源：European Journal of Medicinal Chemistry, 2015, 92: 565-574.

DOI：10.1016/j.ejmech.2015.01.029

• < alpha-Methylidene-< gamma > -lactams
• Pyrazolidinones
• Cytotoxicity
• Structure-activity relationship

Three series of new 4-methylidenepyrazolidin-3-ones with various substitution patterns were synthesized and tested for the cytotoxic activity against two human leukemia cell lines NALM-6 and HL-60 as well as MCF-7 breast cancer cell line. Several obtained methylidenepyrazolidinones exhibited high cytotoxic activity with IC50 values below 10 mu M, mainly against HL-60 leukemia cell line and two of them, 18d,e, displayed IC50 <= 5 mu M, against all tested cell lines. Structure activity relationship studies revealed that the presence of phenyl substituents on both ring nitrogen atoms and vinyl or phenyl substituents in position 5 are crucial for high activity. Selected methylidenepyrazolidinones were also tested on normal human umbilical vein endothelial cells (HUVEC) and pyrazolidinone 18a was found to be 5-fold more toxic against HL-60 than normal cells.

• 出版日期2015-3-6