title: Design, synthesis and cytotoxic evaluation of 4-methylidenepyrazolidin-3-ones.
abstract: 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 μM, mainly against HL-60 leukemia cell line and two of them, 18d,e, displayed IC50 ≤ 5 μM, 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.
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Łódź, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Modranka
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Łódź, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Jakubowski
authors.affiliation: Department of Pharmaceutical Biochemistry, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Różalski
authors.affiliation: Department of Pharmaceutical Biochemistry, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Krajewska
authors.affiliation: Department of Biomolecular Chemistry, Medical University of Łódź, Mazowiecka 6/8, 92-215 Łódź, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Janecka
authors.affiliation: Department of Biomolecular Chemistry, Medical University of Łódź, Mazowiecka 6/8, 92-215 Łódź, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gach
authors.affiliation: Department of Biomolecular Chemistry, Medical University of Łódź, Mazowiecka 6/8, 92-215 Łódź, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Pomorska
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Łódź, Poland. Electronic address: tomasz.janecki@p.lodz.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Janecki
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles
keywords: <alpha-Methylidene-<gamma>-lactams; Cytotoxicity; Pyrazolidinones; Structure–activity relationship