81743-88-6Relevant articles and documents
Structure-Guided Discovery of the Novel Covalent Allosteric Site and Covalent Inhibitors of Fructose-1,6-Bisphosphate Aldolase to Overcome the Azole Resistance of Candidiasis
Cao, Hongxuan,Chen, Han,Han, Xinya,Huang, Yunyuan,Liu, Jiaqi,Peng, Chao,Rao, Li,Ren, Yanliang,Sheng, Chunquan,Su, Chen,Tu, Jie,Wan, Chen,Wan, Jian,Wen, Wuqiang
, p. 2656 - 2674 (2022/02/09)
Fructose-1,6-bisphosphate aldolase (FBA) represents an attractive new antifungal target. Here, we employed a structure-based optimization strategy to discover a novel covalent binding site (C292 site) and the first-in-class covalent allosteric inhibitors
Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors
Bray, William,Carlin, Aaron F.,Clark, Alex E.,Endsley, Mark,Huante, Matthew B.,Huff, Sarah,Kummetha, Indrasena Reddy,Rana, Tariq M.,Smith, Davey,Tiwari, Shashi Kant,Wang, Shaobo
supporting information, (2021/10/20)
The emergence of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an urgent public health crisis. Without available targeted therapies, treatment options remain limited for COVID-19 patients. Using medicinal chemistry and rational drug design strategies, we identify a 2-phenyl-1,2-benzoselenazol-3-one class of compounds targeting the SARS-CoV-2 main protease (Mpro). FRET-based screening against recombinant SARS-CoV-2 Mpro identified six compounds that inhibit proteolysis with nanomolar IC50 values. Preincubation dilution experiments and molecular docking determined that the inhibition of SARS-CoV-2 Mpro can occur by either covalent or noncovalent mechanisms, and lead E04 was determined to inhibit Mpro competitively. Lead E24 inhibited viral replication with a nanomolar EC50 value (844 nM) in SARS-CoV-2-infected Vero E6 cells and was further confirmed to impair SARS-CoV-2 replication in human lung epithelial cells and human-induced pluripotent stem cell-derived 3D lung organoids. Altogether, these studies provide a structural framework and mechanism of Mpro inhibition that should facilitate the design of future COVID-19 treatments.
Synthesis of new alkylated and methoxylated analogues of ebselen with antiviral and antimicrobial properties
Pietka-Ottlik, Magdalena,Burda-Grabowska, Ma?gorzata,Wo?na, Marta,Waleńska, Joanna,Kaleta, Rafa?,Zaczyńska, Ewa,Piasecki, Egbert,Giurg, Miros?aw
, p. 546 - 556 (2017/03/14)
A series of new mono and disubstituted alkylated and methoxylated benzisoselanzol-3(2H)-ones and bis(2-carbamoylaryl)diselenides were prepared in yields ranging from 55% to 95% starting from anthranilic acid and were evaluated for antiviral and antimicrobial activity. The compounds exhibited antiviral activity against Human herpes virus 1 and Encephalomyocarditis virus as well as antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Candida albicans. (Chemical Equation Presented).