z-logo
open-access-imgOpen Access
Design, 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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here