2. Academic Validation
  3. Harzianoic acids A and B, new natural scaffolds with inhibitory effects against hepatitis C virus

Harzianoic acids A and B, new natural scaffolds with inhibitory effects against hepatitis C virus

  • Bioorg Med Chem. 2019 Feb 1;27(3):560-567. doi: 10.1016/j.bmc.2018.12.038.
Bo Li 1,  Li Li 2,  Zonggen Peng 3,  Dong Liu 1,  Longlong Si 1,  Jing Wang 1,  Bochuan Yuan 1,  Jian Huang 1,  Peter Proksch 4,  Wenhan Lin 5
Affiliations

Affiliations

  • 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.
  • 5 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China. Electronic address: whlin@bjmu.edu.cn.
PMID: 30606673 DOI: 10.1016/j.bmc.2018.12.038
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.

Keywords

Anti-HCV activity; Fungus; Harzianoic acids A and B; Mode of action; Sesquiterpene; Structural elucidation; Trichoderma harzianum.

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