Synthesis and biological evaluation of 4-aryl-5-cyano-2H-1,2,3-triazoles as inhibitor of HER2 tyrosine kinase.
4-Aryl-5-cyano-2H-1,2,3-triazoles bearing a variety of substituting groups on 4-phenyl were synthesized. The chemicals, designed as HER2 tyrosine kinase inhibitors, were screened for bioactivity of inhibiting growth of breast cancer MDA-MB-453 cells. The lowest IC(50) value of inhibiting HER2 tyrosine kinase phosphorylation in breast cancer cells is 6.6microM and the IC(50) value of cell growth inhibition is correspondingly 30.9microM. The lipophilicity of substituting groups on triazoles is the main factor to influence their bioactivities.
Cheng
Zhi-Yi
ZY
School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510080, China. chengzhy@mail.sysu.edu.cn
Li
Wen-Jie
WJ
He
Feng
F
Zhou
Jun-Min
JM
Zhu
Xiao-Feng
XF
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004791:Enzyme Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D014230:Triazoles