Six pairs of α-pyrone meroterpenoid dimers from Hypericum monogynum with anti-neuroinflammatory activity

Abstract

Hypericumonates A–F (1–6), six pairs of new α-pyrone meroterpenoid dimers, along with four possible precursors (7–10) were isolated from the leaves and twigs of Hypericum monogynum. Hypericumonates A–C, the first α-pyrone meroterpenoid dimers with two motifs (a 6/6/4-6/6 ring system) connected via C-8–C-9, were proposed via [2 + 2] cycloaddition of α-pyrone meroterpenoid. Their structures were determined by spectroscopic analysis, quantum chemical calculations, and single-crystal X-ray diffraction analysis. From biosynthesis analysis, five pairs of new α-pyrone meroterpenoid dimers (1–5) are derived from a new isopentenyl-α-pyrone (7). Compounds 2 is an unusual homodimer, whereas compounds 1 and 3–6 represent rare heterodimers. Inspired by the traditional anti-inflammatory usages of H. monogynum, all dimers except for 6 were discovered to show good NO inhibitory effect with IC₅₀ values of 2.41 ± 0.31 μM to 14.25 ± 1.93 μM, better than the positive control, minocycline (IC₅₀: 19.09 ± 1.34 μM). Further mechanistic study implied that (+)-1 could prohibit the expression of iNOS and COX-2 in BV-2 cells, and the molecular docking study implied the possible interaction between (+)-1/(−)-1 and these two proteins.