91961-09-0Relevant articles and documents
Discovery of Small Molecules for Repressing Cap-Independent Translation of Human Vascular Endothelial Growth Factor (hVEGF) as Novel Antitumor Agents
Wang, Shi-Ke,Wu, Yue,Wang, Xiao-Qin,Kuang, Guo-Tao,Zhang, Qi,Lin, Shu-Ling,Liu, Hui-Yun,Tan, Jia-Heng,Huang, Zhi-Shu,Ou, Tian-Miao
, p. 5306 - 5319 (2017)
Angiogenesis is important in tumorigenesis and tumor progression. Human vascular endothelial growth factor (hVEGF) is an angiogenic growth factor that plays a crucial role in tumor progression. The G-rich region within the 5′-untranslated regions (5′-UTR) of hVEGF-A mRNA can form a "switchable" RNA G-quadruplex structure that is essential for a cap-independent translation initiation. We screened our small-molecule library for binders of this G-tract. One novel quinazoline derivative, compound 1, showed a significant specific interaction with the G-tract and destabilized the G-quadruplex structure. The results of cellular experiments revealed that compound 1 down-regulated hVEGF-A translation and significantly impeded tumor cells migration. We also found that compound 1 exhibited tumor-inhibiting activity in MCF-7 xenograft tumors, which might be related to its ability to reduce hVEGF expression. These findings present a new strategy of hVEGF-A translational control in which small molecules interact with G-quadruplex structure in the 5′UTR.
N-(4-(quinazolin-2-yl)phenyl)benzamide derivatives with potent anti-angiogenesis activities: Synthesis and evaluation
Sun, Ming,Lv, Na,Li, Zeng,Xiong, Qiru,Xu, Liang,Yin, Zongsheng
, p. 753 - 761 (2016/02/20)
Expanding our studies on the anti-angiogenesis activities of 2,4-disubstituted quinazoline derivatives [8], a series of novel N-(2-(quinazolin-2-yl)phenyl)benzamide (SZ) derivatives were designed and synthesized. Cytotoxicity assays indicated that most of these compounds displayed similar cytotoxicity against tumor cells in comparison with our previously reported, but showed a higher cytotoxicity against HUVECs. The SZ derivatives showed a remarkable inhibitive effect against the migration and adhesion of HUVECs, in addition to demonstrating significant in vivo anti-angiogenesis activities in the chick embryo chorioallantoic membrane (CAM) assay. The results proved that the introduction of an aryl group with a basic amide side chain on the 4′ position linked to the amide of the C-2 substituted quinazoline scaffold is an effective approach to improve the anti-angiogenic activity of quinazoline derivatives.
Design, synthesis and biological evaluation of 4-anilinoquinazoline derivatives as new c-myc G-quadruplex ligands
Jiang, Yin,Chen, Ai-Chun,Kuang, Guo-Tao,Wang, Shi-Ke,Ou, Tian-Miao,Tan, Jia-Heng,Li, Ding,Huang, Zhi-Shu
, p. 264 - 279 (2016/07/07)
A series of 4-anilinoquinazoline derivatives were designed and synthesized as novel c-myc promoter G-quadruplex binding ligands. Subsequent biophysical and biochemical evaluation demonstrated that the introduction of aniline group at 4-position of quinazoline ring and two side chains with terminal amino group improved their binding affinity and stabilizing ability to G-quadruplex DNA. RT-PCR assay and Western blot showed that compound 7a could down-regulate transcription and expression of c-myc gene in Hela cells, which was consistent with the behavior of an effective G-quadruplex ligand targeting c-myc oncogene. More importantly, RTCA and colony formation assays indicated that 7a obviously inhibited Hela cells proliferation, without influence on normal primary cultured mouse mesangial cells. Flow cytometric assays suggested that 7a induced Hela cells to arrest in G0/G1 phase both in a time-dependent and dose-dependent manner.
Synthesis and evaluation of 2,4-disubstituted quinazoline derivatives with potent anti- Angiogenesis activities
Yu, Guangjin,Li, Zeng,Tang, Liang,Xiong, Qiru
, p. 8916 - 8932 (2014/08/05)
A series of 2,4-disubstituted quinazoline derivatives were designed and synthesized. The biological results showed that most of quinazoline derivatives exhibited potent antiproliferative activities against a panel of three tumor cell lines and a good inhibitory effect against the adhesion and migration of human umbilical vein endothelial cells (HUVECs). Among these compounds, 11d was the most potent agent, that also exhibited the highest anti- Angiogenesis activities in the chick embryo chorioallantoic membrane (CAM) assay.
New quinazoline derivatives for telomeric G-quadruplex DNA: Effects of an added phenyl group on quadruplex binding ability
He, Jin-Hui,Liu, Hui-Yun,Li, Zeng,Tan, Jia-Heng,Ou, Tian-Miao,Huang, Shi-Liang,An, Lin-Kun,Li, Ding,Gu, Lian-Quan,Huang, Zhi-Shu
, p. 1 - 13 (2013/07/27)
To improve the selectivity of indoloquinoline or benzofuroquinoline derivatives, we previously reported several quinazoline derivatives [17]. These compounds could mimic a tetracyclic aromatic system through intramolecular hydrogen bond. Studies showed that these quinazoline derivatives were effective and selective telomeric G-quadruplex ligands. With this encouragement, here we synthesized a series of N-(2-(quinazolin-2-yl)phenyl)benzamide (QPB) compounds as modified quinazoline derivatives. In this modification, a phenyl group was introduced to the aromatic core. The evaluation results showed that part of QPB derivatives had stronger binding ability and better selectivity for telomeric G-quadruplex DNA than LZ-11, the most potential compound of reported quinazoline derivatives. Furthermore, telomerase inhibition of QPB derivatives and their cellular effects were studied.
