SARS-CoV 3CL(pro) inhibitory effects of quinone-methide triterpenes from Tripterygium regelii

초록

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 IC50 values of 10.3, 5.5, 9.9, and 2.6 mu M, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC50 = 21.7 mu M). 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. (C) 2010 Elsevier Ltd. All rights reserved.

키워드