Premium
Biological evaluation of novel selenazole‐based compounds as potential thioredoxin reductase inhibitors
Author(s) -
Li DongDong,
He Jie,
Zeng HuiHui
Publication year - 2012
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.2910
Subject(s) - thioredoxin reductase , thioredoxin , chemistry , reductase , ribonucleotide reductase , biochemistry , enzyme , ferredoxin thioredoxin reductase , pharmacology , biology , protein subunit , gene
Recently, thioredoxin reductase as a target for treatment of tumors has attracted the attention of scientists. 1,2‐[Bis(1,2‐benzisoselenazolone‐3(2 H )‐ketone)]ethane (ethaselen, BBSKE, PCT: CN02/00412), designed and synthesized previously, is an effective thioredoxin reductase inhibitor; presently it is in phase II clinical trials, targeting gastric cancer, lung cancer and colon cancer. To seek more novel and effective anticancer drugs, we have developed many selenazole‐based compounds. Evaluation of the thioredoxin reductase inhibitory effect and investigation of the mechanism of anticancer drugs require abundant thioredoxin reductase, but since commercial thioredoxin reductase is expensive its use is often limited. Therefore, the preparation of thioredoxin reductase is necessary. Base on the above investigation, in this work we have prepared thioredoxin reductase and evaluated selenazole‐based compounds, and found that 44 compounds have high inhibitory effect on thioredoxin reductase with IC 50 < 10 µ m , of which 16 compounds have IC 50 values below 1 µ m . This is helpful in investigating and elucidating the mechanism of this kind of compound. Copyright © 2012 John Wiley & Sons, Ltd.