81329-92-2Relevant academic research and scientific papers
Synthesis and biological evaluation of ebselen and its acyclic derivatives
Chang, Tsu-Chung,Huang, Mei-Lan,Hsu, Wen-Lin,Hwang, Jing-Min,Hsu, Ling-Yih
, p. 1413 - 1416 (2003)
Five ebselen and three acyclic ebselen derivatives were synthesized. These compounds were screened for their glutathione peroxidase (GSH Px)-like activity and scavenging activity against 1,1-diphenyl-2-pycryl-hydrazyl (DPPH) and peroxynitrite radical. All tested compounds displayed similar significant GSH Px-like activity, which are slightly higher than that of ebselen. The peroxynitrite scavenging activity showed that the acyclic allylseleno 4c was five times more potent than ebselen.
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
, (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.
