title: Synthesis and in vitro cytotoxic evaluation of novel N-(3,4,5-trimethoxyphenyl)pyridin-2(1H)-one derivatives.
abstract: A series of novel [Formula: see text]-(3,4,5-trimethoxyphenyl)pyridin-2([Formula: see text])-one derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity against human colon cancer cells HCT-116. The key steps involved consecutive Chan-Lam- and Buchwald-Hartwig couplings. Most of these C-6 substituted pyridone derivatives showed moderate antiproliferative activity. The preliminary SAR indicated that the conformationally restricted pyridones exhibited more potent cytotoxicity than the flexible counterparts. In addition, cell cycle analysis of the selected compounds 4b and e showed a G2/M arrest, suggesting a possible antitubulin mechanism for these novel pyridone derivatives.
authors.affiliation: Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
authors.forename: Taijie
authors.initials: T
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Youhong
authors.initials: Y
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D008968:Molecular Conformation; D011728:Pyridones / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D011728:Pyridones; D014404:Tubulin; D050257:Tubulin Modulators