Open AccessDesign, synthesis, and biological evaluation of 3-vinyl-quinoxalin-2(1H)-one derivatives as novel antitumor inhibitors of FGFR1
Author(s) -
Zhiguo Liu,
Shufang Yu,
Di Chen,
Shen Guo-liang,
Yu Wang,
Ling Hou,
Dan Lin,
JinSan Zhang,
Faqing Ye
Publication year - 2016
Publication title -
drug design, development and therapy
Language(s) - English
Resource type - Journals
ISSN - 1177-8881
DOI - 10.2147/dddt.s88587
Subject(s) - quinazolinone , quinoxaline , chemistry , in vitro , cytotoxicity , cancer cell lines , combinatorial chemistry , stereochemistry , cell culture , ic50 , kinase , docking (animal) , structure–activity relationship , biochemistry , cancer cell , cancer , organic chemistry , biology , medicine , nursing , genetics
FGFR1 is well known as a molecular target in anticancer drug design. TKI258 plays an important role in RTK inhibitors. Utilizing TKI258 as a lead compound that contains a quinazolinone nucleus, we synthesized four series of 3-vinyl-quinoxalin-2(1H)-one derivatives, a total of 27 compounds. We further evaluated these compounds for FGFR1 inhibition ability as well as cytotoxicity against four cancer cell lines (H460, B16-F10, Hela229, and Hct116) in vitro. Some compounds displayed good-to-excellent potency against the four tested cancer cell lines compared with TKI258. Structure-activity relationship analyses indicated that small substituents at the side chain of the 3-vinyl-quinoxalin-2(1H)-one were more effective than large substituents. Lastly, we used molecular docking to obtain further insight into the interactions between the compounds and FGFR1.