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

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 6; pp. 1873 - 1876
• Main Authors: Ryu, Young Bae, Park, Su-Jin, Kim, Young Min, Lee, Ju-Yeon, Seo, Woo Duck, Chang, Jong Sun, Park, Ki Hun, Rho, Mun-Chual, Lee, Woo Song
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 2010
• Subjects: 3CL pro; Celastrol; Iguesterin; Quinone-methide; SARS-CoV; Tripterygium regelii; IC 50; NMR; Quinone-methide; K i; Tripterygium regelii; V max; Celastrol; SARS-CoV; 3CL pro; K m; Iguesterin
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.01.152

The presence of a quinone-methide moiety appears to play a relatively significant role in 3CL pro inhibition. 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 μM, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC 50 = 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.