755722-84-0Relevant articles and documents
Inhibitory effect of flavonoids on human glutaminyl cyclase
Li, Manman,Dong, Yao,Yu, Xi,Zou, Yongdong,Zheng, Yizhi,Bu, Xianzhang,Quan, Junmin,He, Zhendan,Wu, Haiqiang
, p. 2280 - 2286 (2016)
Glutaminyl cyclase (QC) plays an important role in the pathogenesis of Alzheimer's disease (AD) and can be a potential target for the development of novel anti-AD agents. However, the study of QC inhibitors are still less. Here, phenol-4′ (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives were synthesized as a new class of human QC (hQC) inhibitors. The efficacy investigation of these compounds was performed by spectrophotometric assessment and the structure-activity relationship (SAR) was evaluated. Molecular docking was also carried out to analyze the binding mode of the synthesized flavonoid to the active site of hQC.
Discovery of naturally occurring aurones that are potent allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase
Haudecoeur, Romain,Ahmed-Belkacem, Abdelhakim,Yi, Wei,Fortuné, Antoine,Brillet, Rozenn,Belle, Catherine,Nicolle, Edwige,Pallier, Coralie,Pawlotsky, Jean-Michel,Boumendjel, Ahcène
scheme or table, p. 5395 - 5402 (2011/10/02)
We have identified naturally occurring 2-benzylidenebenzofuran-3-ones (aurones) as new templates for non-nucleoside hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors. The aurone target site, identified by site-directed mutagenesis, is located in thumb pocket I of HCV RdRp. The RdRp inhibitory activity of 42 aurones was rationally explored in an enzyme assay. Molecular docking studies were used to determine how aurones bind to HCV RdRp and to predict their range of inhibitory activity. Seven aurone derivatives were found to have potent inhibitory effects on HCV RdRp, with IC50 below 5 μM and excellent selectivity index (inhibition activity versus cellular cytotoxicity). The most active aurone analogue was (Z)-2-((1-butyl-1H-indol-3-yl)methylene)-4,6-dihydroxybenzofuran-3(2H)-one (compound 51), with an IC50 of 2.2 μM. Their potent RdRp inhibitory activity and their low toxicity make these molecules attractive candidates as direct-acting anti-HCV agents.