Synthesis, biological evaluation and molecular docking studies of amide-coupled benzoic nitrogen mustard derivatives as potential antitumor agents.
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.
Zheng
Qing-Zhong
QZ
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Zhang
Fei
F
Cheng
Kui
K
Yang
Ying
Y
Chen
Yu
Y
Qian
Yong
Y
Zhang
Hong-Juan
HJ
Li
Huan-Qiu
HQ
Zhou
Chang-Fang
CF
An
Shu-Qing
SQ
Jiao
Qing-Cai
QC
Zhu
Hai-Liang
HL
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
D000577:Amides; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D009588:Nitrogen Mustard Compounds; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases