Discovery and SAR Study of Quinoxaline-Arylfuran Derivatives as a New Class of Antitumor Agents.

Content Provider	Europe PMC
Author	Fan, Dongmei Liu, Pingxian Jiang, Yunhan He, Xinlian Zhang, Lidan Wang, Lijiao Yang, Tao
Editor	Tomašič, Tihomir
Copyright Year	2022
Abstract	A novel class of quinoxaline–arylfuran derivatives were designed, synthesized, and preliminarily evaluated for their antiproliferative activities in vitro against several cancer cell lines and normal cells. The representative derivative QW12 exerts a potent antiproliferative effect against HeLa cells (IC50 value of 10.58 μM), through inducing apoptosis and triggering ROS generation and the accumulation of HeLa cells in vitro. Western blot analysis showed that QW12 inhibits STAT3 phosphorylation (Y705) in a dose-dependent manner. The BLI experiment directly demonstrated that QW12 binds to the STAT3 recombination protein with a KD value of 67.3 μM. Furthermore, molecular docking investigation showed that QW12 specifically occupies the pY+1 and pY-X subpocket of the SH2 domain, thus blocking the whole transmission signaling process. In general, these findings indicated that the study of new quinoxaline–aryfuran derivatives as inhibitors of STAT3 may lead to new therapeutic medical applications for cancer in the future.
Journal	Pharmaceutics
Volume Number	14
PubMed Central reference number	PMC9698340
Issue Number	11
PubMed reference number	36365238
e-ISSN	19994923
DOI	10.3390/pharmaceutics14112420
Language	English
Publisher	MDPI
Publisher Date	2022-11-09
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2022 by the authors.
Subject Keyword	antitumor agent quinoxaline–arylfuran ROS drug discovery
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science