Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry

et al. 2020

Preprint

Zanthoxylum nitidium (Roxb.) DC (Rutaceae) is well known for inhibiting the proliferation of human gastric, liver, kidney and lung cancer cells, though research on its potential use in treating leukaemia is relatively rare. Twenty-six compounds were isolated from the chloroform and petroleum ether extracts of the roots and leaves of Z. nitidium. They were (+)-9′-O-transferuloyl-5, 5′-dimethoxylaricriresinol (1), 8-(3′-oxobut-1′-en-1′-yl)-5, 7-trimethoxy-coumarin (2), 5, 7, 8-trimethoxy-coumarin (3), 5-(3′, 3′-dimethyl-2′-butenyloxy)-7, 8-dimethoxy-coumarin (4), 2-(5-methoxy-2-methyl-1H-indol-3-yl) methyl acetate (5), 2′-(5,6-dihydrochleletrythrine-6-yl) ethyl acetate (6), 6-acetonyldi-hydrochelerythrine (7), 6β-hydroxymethyldihydronitidine (8), bocconoline (9), zanthoxyline (10), O-methylzanthoxyline (11), rhoifoline B (12), N-nornitidine (13), nitidine (14), chelerythrine (15), 4-hydroxyl-7,8-dimethoxy-furoquinoline (16), dictamnine (17), γ-fagarine (18), skimmianine (19), robustine (20), R-(+)-platydesmine (21), 4-O-methyl-1-methyl-quinoline-2-one (22), 4-methoxy-2-quinolone (23), liriodenine (24), aurantiamide acetate (25), 10-O-demethyl-12-O-methylarnottianamide (26). Four among them, compounds 4-6 and 16, were first confirmed in this study by UV, IR, 1D, 2D NMR and HR-ESI-MS spectra. Compounds 1-2 and 11 were isolated from Z. nitidium for the first time. Of the assayed compounds, 1, 2, 9, 10, 14, 15 and 24, exhibited good inhibitory activities in the leukaemia cell line HEL, whereas compound 14 (IC50: 3.59 µM) and compound 24 (IC50: 15.95 µM) exhibited potent inhibitory activities. So, to further investigate the possible mechanisms, cell cycle and apoptosis assays were performed, which indicated that compound 14 causes obvious S-phase arrest in HEL cells and induced apoptosis, whereas compound 24 only induced apoptosis. The present results suggested both compounds 14 and 24 are promising potential anti-leukaemia drug candidates.

Section: < Table 3 >supporting

confidence: 87%

Active constituents of Zanthoxylum nitidum from Yunnan Province against leukemia

et al. 2020

Preprint

“…These results indicated that the two -OCH 3 groups were at C-7 and C-8. The above nuclear magnetic resonance data showed compound 16 was consistent with 4-hydroxy-7, 8-demethy-furoquinoline, which has been previously reported in the literature[14], but no its 1D and 2D NMR data attribution was performed on it. Herein, its NMR data of compound 16 was also assigned.By the comparison of their NMR data with those described in the literature, twenty-six compoundswere identified as (+)-9′-O-transferuloyl-5, 5′-dimethoxylaricriresinol (1) [15], 8-(3′-oxobut-1′-en-1′yl)-5, 7-trimethoxy-coumarin (2) [16], 5, 7, 8-trimethoxy-coumarin (3) [14], 5-(3', 3'-dimethyl-2'butenyloxy)-7, 8-trimethoxy-coumarin (4), methyl 2-(5-methoxy-2-methyl-1H-indol-3-yl) acetate (5), ethyl 2′-(5, 6-dihydrochleletrythrine-6-yl) acetate (6), 6-acetonyldi-hydrochelerythrine (7) [18], 6βhydroxymethyldihydronitidine (8) [19], bocconoline (9) [20], zanthoxyline (10) [21], O-methylzanthoxyline (11) [21], rhoifoline B (12) [22], N-nornitidine (13) [23], nitidine (14) [24], chelerythrine (15) [25], 4-hydroxyl-7, 8-demethyfuroquinoline (16), dictamnine (17) [26], γ-fagarine (18) [27], skimmianine (19) [13], robustine (20) [26], R-(+)-platydesmine (21) [28], 4-O-methyl-1methyl-quinoline-2-one (22) [27], 4-methoxy-2-quinolone (23) [29], liriodenine (24) [30], aurantiamide acetate (25) [31], and 10-O-demethyl-12-O-methylarnottianamide (26) [32].…”

supporting

confidence: 87%

“…The NMR data of compound 6was assigned firstly according to its 2D-NMR. From the 1 H NMR data in Table 3, the coupling constant between the proton signals at δ demethy-furoquinoline, which has been previously reported in the literature [14].…”

Section: < Table 3 >mentioning

confidence: 76%

“…Just like compound 4, the 13C-NMR data of compound 5 was missing in the previous literature, and the 1D and 2D NMR data were also detected and analyzed. As shown in Table 2 14), between H-6 (δ H 6.04) and C-6 (δ C 110.83), and between H-7 (δ H 6.98) and C-7 (δ C 100.35) revealed that compound 5 contains an aromatic ring. At the same time, the HMBC data shown in Figure 3 show correlations of H-8 (δ H 3.65) with C-2 (δ C 172.85), C-3 (δ C 128.86), and C-4a (δ C 104.08) and of H-10 (δ H 2.28) with C-4a (δ C 104.08) and C-9 (δ C 133.76), suggesting that the compound contains an indole moiety.…”

Section: < Table 2 >mentioning

confidence: 92%

See 1 more Smart Citation

Active constituents of Zanthoxylum nitidum from Yunnan Province against leukemia

et al. 2020

Preprint

Zanthoxylum nitidium (Roxb.) DC (Rutaceae) is well known for inhibiting the proliferation of human gastric, liver, kidney and lung cancer cells, whereas research on its potential use in treating leukaemia is relatively rare. 26 compounds were isolated from the chloroform and petroleum ether extracts of the roots and leaves of Z. nitidium. The structures of four compounds (4-6 and 16) were confirmed and attributed firstly by UV-visible spectroscopy, 1D and 2D NMR and HR-ESI-MS. Compounds 1-2 and11 were isolated from Z. nitidium for the first time. Of the assayed compounds, compounds 14 and24 showed inhibitory activities against leukaemia HEL cells with IC50 values of 3.59 and 15.95 µM. In addition, to further investigate the possible mechanism, the cell cycle and apoptosis assays were investigated, which indicated that compound14 caused obvious S phase arrest in HEL cells and induced cell apoptosis, but compound 24 induced only cell apoptosis of HEL cells. These results suggested that compounds 14 and 24 were the potential candidates for anti-leukaemia drug for the first time.

“…The IR spectrum showed the absorption bands for an aromatic ring (1516 and 1443 cm −1 ) and an ether (1151 and 1046 cm −1 ). The 1 H NMR data in Table 4 demethy-furoquinoline, which has been previously reported in the literature [14].…”

Section: Chemical Structure Of Compound 16mentioning

confidence: 63%

Active constituents of Zanthoxylum nitidum from Yunnan Province against leukemia

et al. 2020

Preprint

Zanthoxylum nitidium (Roxb.) DC (Rutaceae) is well known for inhibiting the proliferation of human gastric, liver, kidney and lung cancer cells, whereas research on its potential use in treatments of leukaemia targeting Fli-1 gene is relatively rare. 26 compounds were isolated from the chloroform and petroleum ether extracts of the roots and leaves of Z. nitidium . The structures of four compounds ( 4-6 and 16 ) were confirmed and attributed for the first time by UV-visible spectroscopy, 1D and 2D NMR and HR-ESI-MS. Compounds 1-2 and 11 were isolated from Z. nitidium for the first time. Of the assayed compounds, compounds 14 and 24 showed inhibitory activities against leukaemia HEL cells with IC 50 values of 3.59 and 15.95 µM. In addition, to further investigate the possible mechanism, the cell cycle and apoptosis assays were investigated for the first time, which indicated that compound 14 caused obvious S phase arrest in HEL cells and induced cell apoptosis, but compound 24 induced only cell apoptosis of HEL cells. These results suggested that compounds 14 and 24 were the potential candidates for anti-leukaemia drug for the first time.