Bioorganic & Medicinal Chemistry Letters
Volume 20, Issue 6, 15 March 2010, Pages 1873-1876
Young Bae Ryu, Su-Jin Park, Young Min Kim, Ju-Yeon Lee, Woo Duck Seo, Jong Sun Chang, Ki Hun Park, Mun-Chual Rho, Woo Song Lee
Abstract
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 3CLpro inhibitory activities and showed potent inhibitory activities with IC50 values of 10.3, 5.5, 9.9, and 2.6 μM, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC50 = 21.7 μM). 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.
Keyword
SARS-CoV, 3CLpro, Tripterygium regelii, Quinone-methide, Celastrol, Iguesterin