Studies On The Chemical Constituents Of The Rhizomes Of Sophora Tonkinensis And Their Bioactivities

In order to find bioactive components from natural products, we studied systematically on the chemical constituents of the alkaloid extract of the rhizomes of Sophora tonkinensis. Through various chromatographic methods and spectral technologies,42 compounds were isolated and identified, including 5 new compounds and 1 new natural product.S. tonkinensis (Leguminosae) is mainly distributed in Guangxi, Guizhou, Yunnan, Guangdong and Jiangxi provinces of China. Its roots and rhizomes have historically been used for the treatment of pyrexia, inflammation, acute pharyngolaryneal infections and sore throats. Modern scientific studies demonstrated that the plant contains alkaloids, flavonoids and lignans as its major constituents. As the principal bioactive constituents of S. tonkinensis are alkaloids, It possesses a wide range of pharmacological activities, such as antitumor and antiviral activities. To further discover bioactive constituents,42 compounds were isolated from the alkaloid extract of S. tonkinensis. The compounds were identified via physicochemical properties and spectroscopic data analyses, including 27 alkaloids (1-27),5 flavonoids (28-32),4 lignans (33-36) and 6 others (37-42). Their structures were elucidated as (+)-5a-hydroxyoxysophocarpine (1), (-)-12β-hydroxyoxysophocarpine (2), (+)-5a-hydroxylemannine (3), (-)-sophocarpine (4), (-)-5α-hydroxysophocarpine (5), (-)-9a-hydroxysophocarpine (6), (+)-12α-hydroxysophocarpine (7), (-)-12β-hydroxysophocarpine (8), (+)-oxysophocarpine (9), (+)-matrine (10), (+)-sophoranol (11), (+)-9a-hydroxymatrine (12), (-)-14β-hydroxymatrine (13), (+)-oxymatrine (14), (+)-5a-hydroxyoxymatrine (15), (-)-14β-hydroxyoxymatrine (16), (+)-sophoramine (17), (-)-N-methylcytisine (18), (-)-N-ethylcytisine (19), (-)-N-formylcytisine (20), (-)-N-acetylcytisine (21), (-)-N-propionylcytisine (22), (-)-N-hexanoylcytisine (23), (-)-anagyrine (24), 1-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)ethanone (25), cyclo(Pro-Pro) (26), nicotinic acid (27), (3S,4R)-4-hydroxy-7,4’-dimethoxyisoflavan-3’-O-β-D-glucopyranoside (28), (6aR,11aR)-3-O-β-D-glucopyranosylmedicarpin (29), (6aR,11aR)-maackiain (30), trifolirhizin (31), ononin (32), (-)-secoisolariciresinol-4-O-β-D-glucopyranoside (33), (-)-syringaresinol-4-O-β-D-glucopyranoside(34), (-)-syringaresinol-4,4’-di-O-β-D-glucopyranoside(35), (-)-pinoresinol-4,4’-di-O-β-D-glucopyranoside (36),p-hydroxybenzonic acid (37), p-methoxybenzonic acid (38),4-hydroxymethyl-2,6-dimethoxyphenol-1-O-β-D-glucopyranoside (39), coniferin (40), syringin (41), and (6S,9R)-roseoside (42). Compounds 1-3 and 23 were new alkaloids, compound 28 was a new flavonoid, and compound 25 was a new natural product.The major alkaloids isolated from S. tonkinensis were matrine-type alkaloids, which possess multiple chiral centers. The relative configurations of compounds 1-3 were determined by comprehensive analyses of 1D and 2D NMR data, and their absolute configurations were further established by single-crystal X-ray diffraction and ECD data.The assay of the antiviral activities of compounds 1-17 demonstrated that the new alkaloid 2 exhibited significant antiviral activity against Coxsackie virus B3 (CVB3) with IC50 value of 26.62 μM, showed ca.45 times higher activity compared with the positive control ribavirin (RBV). Primary structure-activity relationship (SAR) analyses of the antiviral activities of compounds 1-17 against influenza virus A suggested that the introduction of an α,β carbon-carbon double bond might play an important role in the anti-H3N2 activity. The evaluation of the cytotoxic activities of compounds 18-42 against four human tumor cell lines (T24, HepG2, SPC-A2 and A549) revealed that compounds 20,23,25 and 30 exhibited moderate cytotoxic activity against A549, with IC50 values of 22.05,31.64,23.05 and 24.58μM, respectively.