title: Synthesis and evaluation of isatin derivatives as effective SARS coronavirus 3CL protease inhibitors.
abstract: N-Substituted isatin derivatives were prepared from the reaction of isatin and various bromides via two steps. Bioactivity assay results (in vitro tests) demonstrated that some of these compounds are potent and selective inhibitors against SARS coronavirus 3CL protease with IC50 values ranging from 0.95 to 17.50 microM. Additionally, isatin 4o exhibited more potent inhibition for SARS coronavirus protease than for other proteases including papain, chymotrypsin, and trypsin.
authors.affiliation: Development Center for Biotechnology, 102, Lane 169, Kang Ning St., Xi Zhi 221, Taipei, Taiwan, ROC.
authors.forename: Li-Rung
authors.initials: LR
authors.lastname: Chen
authors.forename: Yu-Chin
authors.initials: YC
authors.lastname: Wang
authors.forename: Yi Wen
authors.initials: YW
authors.lastname: Lin
authors.forename: Shan-Yen
authors.initials: SY
authors.lastname: Chou
authors.forename: Shyh-Fong
authors.initials: SF
authors.lastname: Chen
authors.forename: Lee Tai
authors.initials: LT
authors.lastname: Liu
authors.forename: Ying-Ta
authors.initials: YT
authors.lastname: Wu
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Kuo
authors.forename: Tom Shieh-Shung
authors.initials: TS
authors.lastname: Chen
authors.forename: Shin-Hun
authors.initials: SH
authors.lastname: Juang
mesh_terms: D001665:Binding Sites; D002918:Chymotrypsin / Q000494:pharmacology; D003198:Computer Simulation; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D004789:Enzyme Activation; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D015394:Molecular Structure; D010206:Papain / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014357:Trypsin / Q000494:pharmacology; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D011480:Protease Inhibitors; D014764:Viral Proteins; D007510:Isatin; D010450:Endopeptidases; D002918:Chymotrypsin; D014357:Trypsin; D003546:Cysteine Endopeptidases; D010206:Papain; D000086782:Coronavirus 3C Proteases