Benzoic acid derivatives, acetophenones, and anti-inflammatory constituents from Melicope semecarpifolia

Melicope semecarpifolia (Merr.) T. G. Hartley (Rutaceace) is a small-to-medium-sized evergreen tree, found at low altitude in forests of Taiwan and the Philippines [1]. The roots of this plant have been used as a carminative in folk medicine [2]. In our studies of Formosan plants for in vitro anti-inflammatory activity, M. semecarpifolia was found to be an active species. Investigation of the EtOAc-soluble fraction of the fruits of M. semecarpifolia has led to the isolation of two new benzoic acid derivatives, (E)-3-acetyl-6-(3,7-dimethylocta-2,6-dienyloxy)-2,4-dihydroxybenzoic acid (1) and (E)-3-acetyl-4-(3,7-dimethylocta-2,6-dienyloxy)-2,6-dihydroxybenzoic acid (2), and three new acetophenones, (E)-1-(5-(3,7-dimethylocta-2,6-dienyloxy)-7-hydroxy-2,2-dimethyl-2H-chromen-8-yl)ethanone (3), (E)-1-(5-(3,7-dimethylocta-2,6-dienyloxy)-7-hydroxy-2-methyl-2-(4-methylpent-3-enyl)-2H-chromen-8-yl)ethanone (4), and (R,E)-1-(5-(3,7-dimethylocta-2,6-dienyloxy)-3,7-dihydroxy-2,2-dimethylchroman-8-yl)ethanone (5), and eight known compounds (6–13). The structures of these new compounds were determined through in-depth NMR and mass-spectrometric analyses. 2-(1′-Geranyloxy)-4,6,β-trihydroxyacetophenone (8) was the most effective among the isolated compounds, with IC₅₀ of 0.73±0.29 and 0.60±0.07µg/mL, respectively, against fMLP-induced superoxide anion generation and elastase release. This paper describes the structural elucidation of 1–5 and the anti-inflammatory activities of these compounds.

Acknowledgements: This work was supported by grant from the National Science Council of the Republic of China.

References: 1. Chang, C. E., Hartley, T. G. (1993) Rutaceae in Flora of Taiwan. 2nd ed.; Editorial Committee of the Flora of Taiwan: Taipei, Taiwan, Vol. 3: p 510–544.

2. Kan, W. S. (1970) Manual of Medicinal Plants in Taiwan. Taipei, Taiwan: National Research Institute of Chinese Medicine, Vol. 2: p 374.