Synthesis and biological evaluation of quinazoline and quinoline bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors and EPR bio-probe agents.
4-anilinoquinazoline and 4-anilinoquinoline scaffolds bearing a 2,2,6,6-tetramethylpiperidine-N-oxyl(TEMPO) have been synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase and A431 cell lines. Compared to their corresponding parent compounds, all of the new compounds bearing a TEMPO showed more efficient inhibition for EGFR and A431 cells. Furthermore, we have proved that these molecules bearing a TEMPO can exactly get into A431 cells exerting inhibitory effect that may be used for EPR detecting. In our docking model, quinazolines bearing a TEMPO on either 6- or 3-positions took different linking modes according to EGFR crystal structure. In contrast to their parent compounds, these new TEMPO-derived analogues possessed compatible inhibitory effect that might be useful as potential EGFR inhibitors and as EPR bio-probes.
Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai, PR China.
Siyuan
S
Li
Chunying
C
Guo
Xianqiang
X
Sun
Yaozong
Y
Li
Hongli
H
Zhao
Dongmei
D
Zhan
Minbo
M
Lan
Yun
Y
Tang
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013113:Spin Labels / Q000138:chemical synthesis
D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011804:Quinolines; D013113:Spin Labels; C551336:2,2,6,6-tetramethylpiperidide; D066246:ErbB Receptors