title: Anticancer properties of novel 4-methylene-1,2-diphenylpyrazolidin-3-ones.
abstract: The limited success of the currently used antitumor therapies is the driving force for organic chemists to seek new lead structures with anticancer potential. Two α-methylene-γ-lactams with an additional nitrogen atom in the lactam ring, 5-vinyl-1,2-diphenyl-4-methylenepyrazolidin-3-one (2a) and 5-phenyl-1,2-diphenyl-4-methylenepyrazolidin-3-one (2b) have been synthesized. Their anticancer activity was assessed in MCF-7 cells. Both compounds inhibited cell proliferation and induced DNA damage and apoptosis, with 2a being the more potent analog. Synergistic effects of 2a used in combination with known anticancer drugs, 5-fluorouracil, taxol, and oxaliplatin were evaluated. Compound 2a significantly enhanced the antitumor action of oxaliplatin and 5-fluorouracil, but not taxol.
authors.affiliation: Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gach
authors.affiliation: Central Scientific Laboratory, Division of Public Health, Faculty of Health Sciences, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Szymański
authors.affiliation: Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Pomorska
authors.affiliation: Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Angelika
authors.initials: A
authors.lastname: Długosz
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924, Lodz, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Modranka
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924, Lodz, Poland.
authors.forename: Marlena
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924, Lodz, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Janecki
authors.affiliation: Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Janecka
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D047069:Pyrazolones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000609398:5-vinyl-1,2-diphenyl-4-methylenepyrazolidin-3-one; D000970:Antineoplastic Agents; D047069:Pyrazolones
keywords: DNA damage; anticancer drugs; apoptosis; breast cancer; cell proliferation; α-Methylene-γ-lactams