Premium
Synthesis and Biological Evaluation of Novel 4‐(2‐ F luorophenoxy)‐2‐(1 H ‐tetrazol‐1‐yl)pyridines Bearing Semicarbazone Moieties as Potent Antitumor Agents
Author(s) -
Qin Mingze,
Liao Weike,
Xu Chen,
Fu Baolin,
Ren Jianguo,
Gu Yucheng,
Gong Ping
Publication year - 2013
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.201300188
Subject(s) - semicarbazone , chemistry , stereochemistry , ic50 , sorafenib , potency , biological activity , in vitro , structure–activity relationship , kinase , pharmacology , biochemistry , medicine , biology , hepatocellular carcinoma
A series of 4‐(2‐fluorophenoxy)‐2‐(1 H ‐tetrazol‐1‐yl)pyridines bearing semicarbazone moieties were synthesized and evaluated for their in vitro antitumor potency. Some of the compounds ( 10b , 10c , 10e – 10h , 10m – 10p , 10r , and 11b ) exhibited moderate to excellent antitumor activity as compared to sorafenib and PAC‐1, as well as low levels of toxicity toward the human fetal lung fibroblast cell line WI‐38. The most promising compound 10p (IC 50 = 0.08, 0.36, 0.97 µM) was 45.1‐, 6.1‐, and 2.4‐fold more active than sorafenib (IC 50 = 3.61, 2.19, 2.32 µM), and 17, 3.2, and 2.9 times better than PAC‐1 (IC 50 = 1.36, 1.17, 2.83 µM) against three cancer cell lines (HT‐29, H460, and MKN‐45), respectively. In addition, further studies examining enzymatic activity suggested that the marked pharmacological activity observed might be ascribed to an inhibitory action against CRAf kinase.