Polyacetylenes from Panax stipuleanatus and their Cytotoxic Effects on Human Cancer Cells

Abstract

Panax stipuleanatus Tsai et Feng (Araliaceae) is an herb that grows in Southeast Yunnan, China, and North Vietnam. In China, it has traditionally been used as a tonic and in the treatment of bruises, bleeding, and muscular pain. To date, oleanane-type triterpenoids have been reported to be major components of P. stipuleanatus, and stipuleanosides R1 and R2 were isolated from a methanol extract of this plant. 2 In a previous investigation, we isolated eleven oleanane type triterpenoids from P. stipuleanatus and investigated their cytotoxicity on the HL-60 and HCT-116 cancer cell lines. In the current study, two new polyacetylenes, stipudiol (1) and stipuol (2), together with a polyacetylene, (3R,9R,10R)panaxytriol (3), a sesquiterpene, spathulenol (4), and a fatty acid, and 9-docosenoic acid methyl ester (5) were isolated from the rhizomes of this P. stipuleanatus (Fig. 1). Stipudiol (1) was obtained as yellow oil. The H-NMR spectrum contained the presence of proton signals at δ 5.27 (1H, d, J = 9.9 Hz), 5.49 (1H, d, J = 16.1 Hz), and 5.95 ppm (1H, ddd, J = 16.1, 9.9, 5.2 Hz), two oxygenated proton signals at δ 4.98 (1H, d, J = 5.2 Hz) and 4.20 ppm (1H, dt, J = 5.4, 6.2 Hz), and two olefinic proton signals at δ 5.78 (1H, d, J = 16.4 Hz) and 6.35 ppm (1H, dd, J = 6.2, 16.4 Hz). The C-NMR contained 18 peaks, including four diyne carbon signals at δ 70.9, 73.6, 77.6, and 80.4 ppm, four olefinic carbon signals at δ 108.1, 117.3, 136.0, and 150.0 ppm, and two oxygenated carbon signals at δ 63.7 and 72.1. These signals were assigned to one methyl group, eight methylene groups, five methine carbon atoms, and four alkynyl carbon atoms, in accordance with correlations observed in HMQC spectra. These signals are similar to those of (3R,9R,10R)panaxytriol (3), except for two olefinic signals at δC 108.1 and 150.0 ppm, which were assigned to C-8 and C-9 by analysis of HMBC spectral data (Fig. 2). Furthermore, longrange couplings were observed between one proton signal at δ 5.49 ppm (H-1) and two carbon signals at δ 136.0 (C-2) and 63.7 ppm (C-3), one proton signal at δ 4.98 ppm (H-3) and three carbon signals at δ 117.3 (C-1), 136.0 (C-2) and