Harzianoic acids A and B,new natural scaffolds with inhibitory effects against hepatitis C virus |
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| Authors: | Bo Li Li Li Zonggen Peng Dong Liu Longlong Si Jing Wang Bochuan Yuan Jian Huang Peter Proksch Wenhan Lin |
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| Affiliation: | 1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China;2. Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, PR China;3. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, PR China;4. Institute für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität, 40225 Düsseldorf, Germany |
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| Abstract: | Two new sesquiterpene-based analogues, namely harzianoic acids A (1) and B (2), were isolated from a sponge-associated fungus Trichoderma harzianum. Their structures were determined on the basis of the extensive spectroscopic analyses in association with the ECD data for the configurational assignment. Harzianoic acids A and B were structurally characterized as a sesquiterpene and a norsesquiterpene with a cyclobutane nucleus, which is uncommonly found from nature. Both compounds exhibited the inhibitory activity to reduce the HCV RNA levels with low cytotoxicity. The preliminary investigation of the mode of action revealed that the compounds blocked the entry step in the HCV life cycle, while the viral E1/E2 and the host cell CD81 were the potential target proteins. |
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| Keywords: | Fungus Harzianoic acids A and B Sesquiterpene Structural elucidation Anti-HCV activity Mode of action |
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