title: Synthesis, biological evaluation and molecular docking studies of amide-coupled benzoic nitrogen mustard derivatives as potential antitumor agents.
abstract: A series of amide-coupled benzoic nitrogen mustard derivatives as potential EGFR and HER-2 kinase inhibitors were synthesized and reported for the first time. Some of them exhibited significant EGFR and HER-2 inhibitory activity. Of all the studied compounds, compounds 5b and 5t exhibited the most potent inhibitory activity, which was comparable to the positive control erlotinib. Docking simulation was performed to position compounds 5b and 5t into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicated that some of the benzoic nitrogen mustard derivatives possessed high antiproliferative activity against MCF-7. In particular, compounds 5b and 5t with potent inhibitory activity in tumor growth inhibition may function as potential antitumor agents.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Qing-Zhong
authors.initials: QZ
authors.lastname: Zheng
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.forename: Kui
authors.initials: K
authors.lastname: Cheng
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
authors.forename: Hong-Juan
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Huan-Qiu
authors.initials: HQ
authors.lastname: Li
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Zhou
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: An
authors.forename: Qing-Cai
authors.initials: QC
authors.lastname: Jiao
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D009588:Nitrogen Mustard Compounds; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases