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Synthesis and biological evaluation of novel dasatinib analogues as potent DDR 1 and DDR 2 kinase inhibitors
Author(s) -
Liu Lu,
Hussain Muzammal,
Luo Jinfeng,
Duan Anna,
Chen Chaonan,
Tu Zhengchao,
Zhang Jiancun
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12863
Subject(s) - dasatinib , chemistry , k562 cells , inhibitory postsynaptic potential , cell culture , kinase , ic50 , cell , in vitro , biochemistry , biology , signal transduction , tyrosine kinase , genetics , neuroscience
Novel dasatinib analogues as DDR 1 and DDR 2 inhibitors were designed and synthesized. The synthesized compounds were screened for DDR 1 and DDR 2 kinase inhibitory and cancer cell proliferation inhibitory activities. Some of the compounds showed the potent inhibitory activities against both DDR 1 and DDR 2, as well as anticancer activity in low nanomolar range against K562 cell line; especially, compound 3j demonstrated significantly better inhibitory potency than the parental dasatinib against both DDR s and also demonstrated the potent inhibitory activity against K562 cell lines ( IC 50 values of 2.26±0.46 n m for DDR 1, 7.04±2.90 n m for DDR 2, and 0.125±0.017 n m for K562 cell line).