Chromenylchalcones showing cytotoxicity on human colon cancer cell lines and in silico docking with aurora kinases

被引：40
|
作者：
Shin, Soon Young [1 ]
Yoon, Hyuk [2 ]
Ahn, Seunghyun [3 ]
Kim, Dong-Wook [4 ]
Kim, Sang Ho [4 ]
Koh, Dongsoo [3 ]
Lee, Young Han [1 ]
Lim, Yoongho [2 ]
机构：
[1] Konkuk Univ, Coll Biol Sci & Biotechnol, Dept Biol Sci, Seoul 143701, South Korea
[2] Konkuk Univ, BMIC, Div Biosci & Biotechnol, Seoul 143701, South Korea
[3] Dongduk Womens Univ, Dept Appl Chem, Seoul 136714, South Korea
[4] Rural Dev Adm, Natl Inst Anim Sci, Suwon 441706, South Korea
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 14期
关键词：
Chalcone; Colorectal cancer; Clonogenicity; In silico docking; Aurora kinase; DERIVATIVES; EXPRESSION; FLAVONOIDS; PREVENT; POTENT;
D O I：
10.1016/j.bmc.2013.04.086
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Due to toxicity problems, various plant-derived compounds have been screened to find the chemotherapeutic agents. As anticancer therapeutic agents, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity. Chromenones show anticancer activities too. Therefore, hybrids of chalcone and chromenone may be potent chemotherapeutic agents. We prepared 16 synthetic chromenylchalcones and applied a clonogenic long-term survival assay method for them on HCT116 human colorectal cancer cell lines. One of chromenylchalcones tested here, chromenylchalcone 11, showed IC50 of 93.1 nM which can be competed with the IC50 values of well-known flavonoids such as catechin gallate and epicatechin gallate. Further biological experiments including cell cycle analysis, apoptosis assay, Western blot analysis, and immunofluorescent microscopy were carried out for this compound. In addition, in vitro kinases binding assay performed to explain its molecular mechanism demonstrated the compound inhibited aurora kinases. The binding modes between chromenylchalcone 11 and aurora kinases were elucidated using in silico docking experiments. These findings could be used for designing cancer therapeutic or preventive plant-derived chromenylchalcone agents. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4250 / 4258
页数：9
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