title: Design, synthesis and biological evaluation of N-phenylsulfonylnicotinamide derivatives as novel antitumor inhibitors.
abstract: A series of novel N-phenylsulfonylnicotinamide derivatives (1-24) have been synthesized and evaluated as potential EGFR tyrosine kinase (TK) inhibitors. Among all the compounds, compound 10 (5-bromo-N-(4-chlorophenylsulfonyl)nicotinamide) showed the most potent growth inhibitory activity against EGFR TK and antiproliferative activity of MCF-7 cancer cell line in vitro, with IC(50) value of 0.09 and 0.07 μM. Docking simulation was performed to insert compound 10 into the EGFR TK active site to determine the probable binding model. Based on the preliminary results, compound 10 with potent inhibitory activity to tumor growth may be a potential anticancer agent.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Zhang
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Liu
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Yang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C572545:N-(phenylsulfonyl)benzamide; D066246:ErbB Receptors