Anticancer Properties of Novel 4-methylene-1,2-diphenylpyrazolidin-3-ones

作者：Gach Katarzyna; Szymanski Jacek; Pomorska Dorota; Dlugosz Angelika; Modranka Jakub; Michalak Marlena; Janecki Tomasz; Janecka Anna^*

来源：Chemical Biology & Drug Design, 2015, 86(5): 961-968.

DOI：10.1111/cbdd.12565

• anticancer drugs
• apoptosis
• breast cancer
• cell proliferation
• DNA damage
• alpha-Methylene-gamma-lactams

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 alpha-methylene-gamma-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.

• 出版日期2015-11