Bruceadysentoside A, a new pregnane glycoside and others secondary metabolites with cytotoxic activity from brucea antidysenterica J. F. Mill. (simaroubaceae)

Abstract

The chemical investigation of the root barks leaves and stem barks of Brucea antidysenterica J. F. Mill. (Simaroubaceae) led to the isolation of a new pregnane glycoside, named Bruceadysentoside A or 3-O-β-L-arabinopyranosyl-pregn-5-en-20-one (1) together with seventeen known compounds. Their structures were established from spectral data, mainly HRESIMS, 1 D and 2 D NMR and by comparison with literature data. Compounds 1, 2, 5, 6, 8, 10, 12 and 13 were tested in vitro for their effects on the viability of two different human cancer cell lines, namely prostate PC-3 adenocarcinoma cells and colorectal HT-29 adenocarcinoma cells. No substantial activities were recorded for 2, 10, 12 and 13 (up to 10 μM concentration). 1, 5 and 8 did not show strong anti-proliferative effects up to 100 μM, however, 6 exhibited a stronger anti-proliferative effect with IC50 values of ∼ 100 μM against PC-3 and ∼ 200 μM against HT-29.

GRAPHICAL ABSTRACT

Keywords:

• Brucea antidysenterica
• Bruceadysentoside A
• cytotoxic activities
• hydnocarpin
• pregnane glycoside
• Simaroubaceae

3. Experimental (supplementary data)

3.1. Bruceadysentoside a or 3-β-L-arabinopyranosyl-pregn-5-ene-3-ol-20-one (1)

C₂₆H₄₀O₆, white amorphous powder; HRESI-MS m/z: 471.2827 [M + Na]⁺ (cald for 471.2723); m/z 299.2444 [M-ara]⁺ (C₂₁H₃₁O⁺). ¹H NMR (600 MHz, pyridine-d5) δ: 0.58 (3H, s, 18-CH3), 0.88 (3H, s, 19-CH3), 0.89 (1H, m, H-9), 0.97 (1H, m, H-14), 1.01 (1H, m, H-1α), 1.07 (1H, m, H-15α), 1.23 (1H, m, H-8), 1.26 (1H, m, H-11α), 1.27 (1H, m, H-12α), 1.28 (1H, m, H-7α), 1.46 (1H, m, H-11β), 1.52 (1H, m, H-7β, 15β), 1.55 (1H, m, H-16α), 1.72 (1H, m, H-1β), 1.73 (2H, m, H-2), 1.92 (1H, m, H-12β), 2.07 (3H, s, 21-CH3), 2.29 (1H, m, H-16β), 2.39 (1H, m, H-4α), 2.44 (1H, t, J = 9.1 Hz, H-17), 2.65 (1H, m, H-4β), 3.77 (1H, t, J = 10.7 Hz, H-5'α), 3.85 (1H, m, H-3), 4.18 (1H, t, J = 8.8 Hz, H-3'), 4.29 (1H, d, m, H-4'), 4.31 (1H, m, H-5'β), 4.42 (1H, t, J = 7.9 Hz, H-2'), 4.82 (1H, d, J = 7.1 Hz, H-1'), 5.32 (1H, brs, H-6); ¹³C NMR (150 MHz, pyridine-d5) δ: 13.0 (C-18), 19.1 (C-19), 21.1(C-11), 22.9 (C-16), 24.4 (C-15), 30.1 (C-2), 31.2 (C-21), 31.7 (C-8), 31.8 (C-7), 36.7 (C-10), 37.4 (C-1), 38.5 (C-12), 39.0 (C-4), 43.7 (C-13), 50.0 (C-9), 56.5 (C-14), 63.4 (C-17), 66.7 (C-5'), 69.3 (C-4'), 72.3 (C-2'), 74.4 (C-3'), 77.7 (C-3), 102.9 (C-1'), 121.4 (C-6), 140.8 (C-5), 208.3 (C-20).

Acknowledgements

YM, JDW and BTN are particularly grateful to the YABINAPA Graduate School for providing research facilities in Cameroon. GWF is thankful to DAAD for a 3 months fellowship in Prof Ludger Wessjohann and Dr. Norbert Arnold laboratory in the Leibniz-Institut für Pflanzenbiochemie (IPB). They are acknowledged for providing facilities for spectroscopic analysis and cytotoxicity screening of some of the isolated compounds. We wish to thank the Alexander von Humboldt Foundation, Germany for Research Group Linkage funding 2015-2018 of the Norbert Sewald-Jean Duplex Wansi research group cooperation and generous support with laboratory equipment.

Disclosure statement

No potential conflict of interest was reported by the authors.