Synthesis of dammarane-type triterpene derivatives and their ability to inhibit HIV and HCV proteases |
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Authors: | Ying Wei Chao-Mei Ma Masao Hattori |
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Affiliation: | 1. Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan;2. Department of Pharmacy, Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Guiyang, Guizhou 550002, China |
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Abstract: | We synthesized dammarane-type triterpene derivatives and evaluated their ability to inhibit HIV-1 and HCV proteases to understand their structure–activity relationships. All of the mono- and di-succinyl derivatives (5a–5f) were powerful inhibitors of HIV-1 protease (IC50 < 10 μM). However, only di-succinyl (5e) and 2,3-seco-2,3-dioic acid (3b) derivatives similarly inhibited HCV protease (IC50 < 10 μM). A-nor dammarane-type triterpenes (4a and 4b, IC50 10.0 and 29.9 μM, respectively) inhibited HIV-1 protease moderately or strongly, but were inactive against HCV protease. All compounds that powerfully inhibited HIV-1 or HCV protease did not appreciably inhibit the general human proteases, renin and trypsin (IC50 > 1000 μM). These findings indicated that the mono-succinyl dammarane type derivatives (5a–5d) selectively inhibited HIV-1 protease and that the di-succinyl (5e, 5f) as well as 2,3-seco-2,3-dioic acid (3b) derivatives preferably inhibited both viral proteases. |
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