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Design, synthesis, and biological evaluation of novel 4‐phenoxypyridine derivatives as potential antitumor agents
Author(s) -
Liu Ju,
Liu Yutong,
Hao Xuechen,
Wang Yang,
Ji Jingchao,
Liu Yajing,
Ding Shi,
Chen Ye
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800338
Subject(s) - cytotoxicity , acridine orange , a549 cell , chemistry , ethidium bromide , apoptosis , moiety , cell culture , cytotoxic t cell , stereochemistry , in vitro , cell cycle , pharmacology , biochemistry , biology , dna , genetics
A series of novel 4‐phenoxypyridine derivatives containing the 4‐oxo‐1,4‐dihydropyridazine‐3‐carboxamide moiety were synthesized and evaluated for their in vitro cytotoxic activity against the A549 cancer cell line, and some compounds were further examined for their cytotoxic activity against the H460, BGC823, MKN45, and HT‐29 cancer cell lines. Most of the compounds exhibited moderate to significant cytotoxicity. The most promising compound 15b (with VEGFR2 inhibitory concentration [IC 50 ] value of 0.23 μM) showed remarkable cytotoxicity against A549, BGC‐823, MKN45, H460, and HT‐29 cells, with IC 50 values of 0.75, 1.68, 2.63, 5.08 and 7.22 μM, respectively. Their preliminary structure‐activity relationship studies indicate that electron‐withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity. Moreover, treatment of A549 cells with compound 15b resulted in cell cycle arrest in the G 0 /G 1 phase in a dose‐dependent manner. Further apoptotic studies and acridine orange/ethidium bromide staining were also performed on A549 cells, which showed that compound 15b could induce apoptosis. Wound‐healing assay results indicated that compound 15b strongly inhibited A549 cell motility.