SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii.
Quinone-methide triterpenes, celastrol (1), pristimerin (2), tingenone (3), and iguesterin (4) were isolated from Triterygium regelii and dihydrocelastrol (5) was synthesized by hydrogenation under palladium catalyst. Isolated quinone-methide triterpenes (1-4) and 5 were evaluated for SARS-CoV 3CL(pro) inhibitory activities and showed potent inhibitory activities with IC(50) values of 10.3, 5.5, 9.9, and 2.6 microM, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC(50)=21.7 microM). As a result, quinone-methide moiety in A-ring and more hydrophobic E-ring assist to exhibit potent activity. Also, all quinone-methide triterpenes 1-4 have proven to be competitive by the kinetic analysis.
Ryu
Young Bae
YB
Eco-Friendly Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Republic of Korea.
Park
Su-Jin
SJ
Kim
Young Min
YM
Lee
Ju-Yeon
JY
Seo
Woo Duck
WD
Chang
Jong Sun
JS
Park
Ki Hun
KH
Rho
Mun-Chual
MC
Lee
Woo Song
WS
D000998:Antiviral Agents / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry*; D008958:Models, Molecular; D010936:Plant Extracts / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*; D029757:Tripterygium / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
D000998:Antiviral Agents; D016227:Benzoquinones; D010936:Plant Extracts; D014315:Triterpenes; C004532:quinone