62581-82-2Relevant articles and documents
Synthesis and Evaluation of Novel Quinazolinone Derivatives as Potential Anti-HCC Agents
Chen, Wang,Gu, Xiaoke,Jiang, Chunyu,Li, Shuqiong,Li, Zheng,Liu, Qingchuan,Qiu, Jingying,Zhou, Qingqing,Zou, Yueting
, (2022/01/06)
Hepatocellular carcinoma (HCC), a common malignancy worldwide, has a high mortality rate and limited effective therapeutic options. In this work, a series of quinazolinone compounds (6a–t and 7a–i) were synthesized as potential anti-HCC agents. Among them, compound 7b more potently inhibited HepG2, HUH7 and SK-Hep-1 cells proliferation than classical anti-HCC drug sorafenib, indicating its potential anti-HCC effect. Interestingly, 7b could dose-dependently decrease Cyclin D1 and CDK2 levels, and increase p21 protein expression, thus inducing HepG2 cells cycle arrest at G0/G1 phase. In addition, 7b also displayed potent apoptosis-induced effect on HepG2 cells by interfering Bad, Bax, Bcl-2 and Bcl-xl proteins expression. Notably, 7b could efficiently block the activity of PI3K pathway by dose-dependently reducing the phosphorylation of PI3K (Y607) and AKT (S473). Moreover, predicted ADME properties indicated that 7b possessed a good pharmacokinetic profile. Collectively, compound 7b might be a promising lead to the development of novel therapeutic agents towards HCC.
Assessment of quinazolinone derivatives as novel non-nucleoside hepatitis B virus inhibitors
Qiu, Jingying,Chen, Wang,Zhang, Yinpeng,Zhou, Qingqing,Chen, Jing,Yang, Lihua,Gao, Jian,Gu, Xiaoke,Tang, Daoquan
, p. 41 - 49 (2019/05/15)
Hepatitis B virus (HBV)infection is a worldwide public health issue. Search for novel non-nucleoside anti-HBV agents is of great importance. In the present study, a series of quinazolinones derivatives (4a-t and 5a-f)were synthesized and evaluated as novel anti-HBV agents. Among them, compounds 5e and 5f could significantly inhibit HBV DNA replication with IC50 values of 1.54 μM and 0.71 μM, respectively. Interestingly, the selective index values of 5f was higher than that of lead compound K284–1405, suggesting 5f possessed relatively safety profile than K284–1405. Notably, 5e and 5f exhibited remarkably anti-HBV activities against lamivudine and entecavir resistant HBV strain with IC50 values of 1.90 and 0.84 μM, confirming their effectiveness against resistant HBV strain. In addition, molecular docking studies indicated that compounds 5e and 5f could well fit into the dimer-dimer interface of HBV core protein dominated by hydrophobic interactions. Notably, their binding modes were different from the lead compound K284–1405, which may be attributed to the additional substituent groups in the quinazolinone scaffold. Taken together, 5e and 5f possessed novel chemical structure and potent anti-HBV activity against both drug sensitive and resistant HBV strains, thus warranting further research as potential non-nucleoside anti-HBV candidates.
A photoactivated molecular gate
Agostini, Alessandro,Sancenon, Felix,Martinez-Manez, Ramon,Marcos, Maria D.,Soto, Juan,Amoros, Pedro
supporting information, p. 12218 - 12221 (2012/11/07)
An o-nitrobenzyl ester derivative bearing a cyclodextrin moiety that was selectively opened by the addition of specific enzymes and by UV irradiation was prepared. On methoxybenzylamine fragment, a compound, which , other than the photo-cleavable group, c
