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

https://doi.org/10.1016/j.bmc.2018.12.038Get rights and content
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Highlights

  • Harzianoic acids A and B are new compounds with unusual cyclobutane nucleus.

  • Harzianoic acids A and B exhibited anti-HCV activities.

  • Harzianoic acids A and B target on entry proteins of virus and host cells.

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

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

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