Herpotriquinones A and B, two dimeric naphthoquinone–epoxycyclohexenone adducts with anti-neuroinflammatory activity from the isopod-associated fungus Herpotrichia sp. SF09

Abstract

Herpotriquinones A and B (1 and 2), two pyran-bridged naphthoquinone–epoxycyclohexenone dimers with an unprecedented 6/6/6/6/6-fused pentacyclic ring skeleton, along with two known precursors (3 and 4) were isolated from the isopod-associated fungus Herpotrichia sp. SF09. Their structures were elucidated by means of spectroscopic data, single-crystal X-ray diffraction, and quantum chemical calculations of ¹³C NMR and electronic circular dichroism (ECD). Herpotriquinones A and B (1 and 2) represent the first examples of polyketide heterodimers biogenetically constructed by a molecule of epoxycyclohexenone with a naphthoquinone unit via a rare formal oxa-[3 + 3] cycloaddition. The density functional theory (DFT) calculations and intermediate-trapping experiment facilitated the proposal of the biosynthetic pathway for these polyketides. In addition, compounds 1 and 2 were found to be potent anti-neuroinflammatory agents in CuSO₄-induced zebrafish and lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Meanwhile, western blot analysis suggested that 1 and 2 could ameliorate the neuroinflammation by suppressing the activation of the NF-κB and MAPK signaling pathways.