Synthesis and evaluation of isatin derivatives as effective SARS coronavirus 3CL protease inhibitors.
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.
Chen
Li-Rung
LR
Development Center for Biotechnology, 102, Lane 169, Kang Ning St., Xi Zhi 221, Taipei, Taiwan, ROC.
Wang
Yu-Chin
YC
Lin
Yi Wen
YW
Chou
Shan-Yen
SY
Chen
Shyh-Fong
SF
Liu
Lee Tai
LT
Wu
Ying-Ta
YT
Kuo
Chih-Jung
CJ
Chen
Tom Shieh-Shung
TS
Juang
Shin-Hun
SH
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*
D011480:Protease Inhibitors; D014764:Viral Proteins; D007510:Isatin; D010450:Endopeptidases; D002918:Chymotrypsin; D014357:Trypsin; D003546:Cysteine Endopeptidases; D010206:Papain; D000086782:Coronavirus 3C Proteases