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.
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