Structural elucidation, bio-inspired synthesis, and biological activities of cyclic diarylpropanes from Horsfieldia kingii.

Bioactivity-guided phytochemical investigation on 70% aqueous acetone extracts of the twigs and leaves of Horsfieldia kingii led to the isolation of two novel cyclic diarylpropanes (1 and 2) bearing a 2,3-dihydro-1 H -indene core, one new diarylpropane (3), six known diarylpropanes (4 – 9), one flavanol (10), and seven lignans (11 – 17). Their structures were determined by extensive spectroscopic analysis, electronic circular dichroism calculations, and X-ray diffraction crystallography. Moreover, a biomimetic synthesis of 1 and 2 were accomplished in four steps. The in vitro nitric oxide production inhibition tests of these compounds revealed that compounds (±)- 2 , (+)- 2 , (−)- 2 , and 10 were potential with IC 50 values lower than 10 μ M. Compound 2 could inhibit iNOS expression in LPS-induced RAW264.7 cells at a series of non-cytotoxic concentrations (<20 μ M). Furthermore, the bioassay results also suggested the primary SARs of 1-phenyl-2,3-dihydro-1 H -indene based scaffold. Image 1 • 17 compounds were isolated from Horsfieldia Kingii. • Horsfielenides C (1) and D (2) were novel cyclic diarylpropanes bearing a 2,3-dihydro-1 H -indene core. • A biomimetic synthesis of 1 and 2 were accomplished in four steps. • Horsfielenide D (2) was the most potential compound to inhibit NO production with IC 50 value of 4.40 ± 0.69 μ M. [ABSTRACT FROM AUTHOR]