Immunosuppressive diarylpropane dimer and spirocyclic-monomers from Horsfieldia kingii

Abstract

Horsfiequinone G (1), a dimeric diarylpropane featuring an unprecedentedly oxo-6/7/6 fused ring system, a new flavane, horsfielenide F (2), three naturally occurring spirocyclic monomers containing all-carbon quaternary centers, horspirotone A (3), horspirotone B (4), and methyl spirobroussonin B (5), along with horsfiequinone A (6) were isolated from Horsfieldia kingii. Their structures and absolute configurations were determined by the inspection of extensive spectroscopic data and electronic circular dichroism (ECD) calculations. Biological evaluations of these isolates revealed that compounds 1 - 3 and 5 - 6 exhibited specifically immunosuppressive activities against Con A-induced T lymphocytes with IC₅₀ values ranging from 2.07 to 12.34 μM (selectivity indices = 2.3-25.2). Compound 1 also suppressed the secretion of inflammatory factors like IL-1β and IL-6 in RAW264.7 cells which could present a new class of nonsteroidal anti-inflammatory agent. Finally, the primary structure-activity relationship (SAR) was also discussed.

Keywords: Anti-inflammation; Dimeric diarylpropane; Horsfieldia kingii; Immunosuppressive activity; Spirocyclic diarylpropane.