title: Design and synthesis of a series of serine derivatives as small molecule inhibitors of the SARS coronavirus 3CL protease.
abstract: Synthesis of serine derivatives having the essential functional groups for the inhibitor of SARS 3CL protease and evaluation of their inhibitory activities using SARS 3CL R188I mutant protease are described. The lead compounds, functionalized serine derivatives, were designed based on the tetrapeptide aldehyde and Bai's cinnamoly inhibitor, and additionally performed with simulation on GOLD softwear. Structure activity relationship studies of the candidate compounds were given reasonable inhibitors ent-3 and ent-7k against SARS 3CL R188I mutant protease. These inhibitors showed protease selectivity and no cytotoxicity.
authors.affiliation: Department of Biological Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan. Electronic address: konno@yz.yamagata-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
authors.affiliation: Department of Biological Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Wakabayashi
authors.affiliation: Department of Biological Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Takanuma
authors.affiliation: Department of Biological Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Yota
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan. Electronic address: akaji@mb.kyoto-phu.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Akaji
mesh_terms: D016923:Cell Death / Q000187:drug effects; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology*; D012694:Serine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; D054852:Small Molecule Libraries; D014764:Viral Proteins; D012694:Serine; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases
keywords: Cathepsin B; Cytotoxicity; Docking simulation; SARS 3CL protease; SARS CoV; Serine derivative