Syntheses of alkyl-de-sanguinarine-N5-methyl derivatives and evaluation of in vitro growth inhibitory activities against cancer cell lines / 药学学报

2,3:7,8-Bis(methylenedioxy)benzo[c]phenanthridine was synthesized in a strategy of converging synthesis with 6-bromo-2,3-dihydroxybenzaldehyde, 5-nitronaphthalene-2,3-diol, and dibromomethane, respectively, as starting materials. The reaction process included dioxy-de-dibromo nucleophilic substitution under alkaline condition, reduction reaction, Schiff base-forming reaction, and an arene radical cyclization step under the presence of Bu3SnH and AIBN as radical initiator, among others. The 2,3:7,8-bis(methylenedioxy)benzo[c] phenanthridine as intermediate was reacted with NaBH4 and different aliphatic acids as alkylation agent to afford 2,3:7,8-bis(methylenedioxy)-5,6-dihydro-N5-alkylbenzo[c]phenanthridines. These dihydro-type products were aromatized using DDQ as oxidant under alkaline condition, and then, salinized using HCl as source of equilibrium anion to yield the series of target alkyl-de-sanguinarine-N5-methyl derivatives. All the synthesized alkyl-de-sanguinarine-N5-methyl derivatives exhibited significantly improved in vitro growth inhibitory activities against cancer cell lines as compared with sanguinarine and the positive control. In pharmacological experiments targeting five cancer cell lines, the target compounds showed activities five-fold active than that of sanguinarine. The findings of this study indicated that the structure modification strategy of substituting n-alkyls for the N5-methyl of natural sanguinarine can be used to improve the growth inhibitory activities against cancer cell lines through increasing liposolubility and steric hindrance to protect the active 5,6-imine structure.

Lignans from cultivated Gynura nepalensis / 中国中药杂志

Taking application of some isolation and purification technologies, including solvent extraction, rude solvent isolation, column chromatographies on silica gel and Sephadex LH-20 , and preparative HPLC , 4 compounds were obtained from Gynura nepalensis cultivated in a suburban area of Beijing. Their structures were identified by spectroscopic methods in conjunction with comparison of the NMR data with literature values as 7S,8R-9'-O-ethyl-dehydrodiconiferyl-9-acetate (1), 9'-O-ethyl-dehydrodiconiferyl alcohol (2), dehydrodiconiferyl-9,9'-diacetate(3), and (+)-medioresinol(4), respectively. 1 is a new 2,3-dihydrobenzofuran-8,3'-neolignane type compound, and 2-4 were isolated from G.nepalensis for the first time. The complete assignment of the 1H- and 13C-NMR spectroscopic data of the four compounds recorded in DMSO-d6 was achieved.

Research on certified reference material of emodin in rhubarb and its alcohol extract, water extract / 中国中药杂志

The certified reference materials (CRMs) of emodin in rhubarb and its alcohol extract, water extract were developed by using quantity transfer technology from single chemical composition to the complex systems. The CRM of emodin was used for quantity transfer, and high performance liquid chromatography (HPLC) method was used to determine the contents of emodin in different matrix composition. By establishing mathematical model and calculating the parts of uncertainty, the uncertainty values were finally gotten. CRMs of emodin in rhubarb, alcohol extract and water extract were accomplished. The content values of emodin were 0.40% ±0.03%, 1.15%±0.18%, 0.16%±0.08% (k=2,P=0.95), respectively. The established method for quantity transfer has successfully solved the technical problems that the value of active ingredient of traditional Chinese medicine can't be traced to SI units. The series of CRMs are assigned as grade primary reference materials, which are useful for quality control of the emodin content, also provide the accurate and reliable CRM, materials standard and standard methods.

Constituents with anti-oxidative activity from seeds of Jufeng grape / 中国中药杂志

Taking application of some isolation and purification technologies, including crushing, solvent extraction, preliminary solvent isolation, column chromatographies over silica gel and Sephadex LH-20 gel and preparative HPLC, 8 compounds were obtained from the seeds of Jufeng grape sourced from market. Their structures were identified by spectroscopic methods and comparison with literature values as Catechin (1), Epicatechin (2), quercetin (3), ethylgallate (4), rel-(2S, 3R) -2-(4-hydroxy-3-methoxyphenyl) -3- (hydroxymethyl)-5-(3-hydroxypropyl)-2,3-dihydrobenzofuran-7-ol (5), rel-(2α, 3β)-7-O-methylcedrusin (6), rel-(1R,2S)-1-(4-hydroxy-3-methoxyphenyl) -2-(4-(3-hydroxypropyl) -2-methoxyphenoxy) propane-1,3-diol (7), and (+) -isolariciresinol (8), respectively. Compounds 5-8 were serial lignans isolated from the seeds of grape for the first time. Structurally, 5 and 6 belong in benzofuran-8,3'-neolignans, 7 in 8,4'-oxyneolignan, and 8 in 8,8' :2,7'-cyclolignan. According to in vitro activity evaluation conducted in cell model, compound 6 showed significant anti-oxidative ability, with the activity of RAW264. 7 cell superoxide dismutase being raised evidently in the test as compared with the positive anti-oxidative agents, compounds 1 and 2.

Chemical constituents of the roots of Macleaya microcarpa and activation efficacy of benzophenanthridine alkaloids for the transcription of xbp1 gene / 药学学报

Ongoing study on the chemical constituents of the roots of Macleaya microcarpa led to the isolation of eight compounds of derivatives of triterpenes and organic acids in addition to some previously identified benzophenanthridines. The eight compounds were identified by spectroscopic methods as well as comparison with literature values as 1-oxo-2, 22 (30)-hopandien-29-oic acid (1), 3-oxo-12-oleanen-30-oic acid (2), 3α-hydroxy-12-oleanen-30-oic acid (3), 3β-hydroxy-12-oleanen-30-oic acid (4), ferulic acid (5), ferulic acid 4-O-β-D-glucoside (6), 3-O-feruloylquinic acid (7), and methyl 3-O-feruloylquinate (8). Of which, 1 is a new triterpenoid of hopanes and 2-8 are isolated from M microcarpa for the first time. In order to discover natural active compounds as potential agents of anti-ulcerative colitis (UC), an in vitro drug high-throughput screening model targeted x-box-binding protein 1 (xbp1) was employed to evaluate the activity of the major chemical constituents of M microcarpa. The result confirmed that two dihydrobenzophenanthridines, dihydrosanguinarine (9) and dihydrochelerythrine (10), showed a certain activity on activating the transcription of xbpl, a transcription factor (TF) associated with the occurrence, development, and potential treatment of UC, with their relative activating ratios being 1.76 and 1.77 times, respectively, as compared with control group.

Study on anti-oxidative effect of extracts from Cichorium endivia on HepG2 cells and its mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of extracts from Cichorium endivia (CEE) in H2O2-induced HepG2 cell oxidative stress injury, and explore the antioxidant mechanism of CEE in HepG2 cells.</p><p><b>METHOD</b>The viability of H2O2-induced HepG2 cells and the intracellular ROS level were measured by MTT assay and DCFH-DA fluorescence staining assay. The antioxidant-response element (ARE)-Luciferase activity was tested in HepG2 cells stably transected by ARE reporter gene. The fluorescence quantitative RT-PCR was adopted to determine the mRNA expressions of genes containing ARE sequence in HepG2 cells.</p><p><b>RESULT</b>The cell viability reduced, while the ROS level increased after HepG2 cells were treated by H2O2. Different concentrations of CEE could be added to significantly improve the above results. After HepG2 cells transected by ARE reporter gene were treated with different concentrations of CEE, the intracellular ARE activity could increase in a concentration-dependent manner. In addition, the mRNA expressions of regulatory genesGCLC, GCLM and HMOX-1 containing ARE sequence in HepG2 cells were up-regulated in a concentration-dependent manner by CEE.</p><p><b>CONCLUSION</b>CEE inhibited the H2O2-injured HepG2 cells by reducing the ROS level. CEE's antioxidant mechanism for HepG2 cells may be closely related to the antioxidant defense system associated with its effect of activating Nrf2-ARE pathway in HepG2 cells.</p>

Study on chemical constituents from cultivated Gynura nepalensis / 中国中药杂志

Taking application of some isolation and purification technologies, such as solvent extraction, preliminary solvent isolation, column chromatographies over silica gel and Sephadex LH-20 gel and preparative HPLC, 10 compounds were obtained from Gynura nepalensis cultivated in the suburban area of Beijing. Their structures were identified by spectroscopic methods and comparison with literature as (3R) -3-hydroxy-β-ionone (1), (3S,5R, 6S, 7E) -5, 6-epoxy-3-hydroxy-7-megastigmen-9-one (2), (+) -boscialin (3), 3, 6-trans-3-hydroxy-α-ionone (4), 3, 6-cis-3-hydroxy-α-ionone (5), 3, 4-cis-3, 4-dihydroxy-β-ionone (6), ethyl caffeate (7), loliolide (8), 1H-indole-3-carbaldehyde (9), and 3-(hydroxyacetyl)indole (10), respectively. All compounds were isolated from the title plant for the first time, and with compounds 1, 2, 4-7, 9 and 10 being isolated from Gynura species for the first time. Structurally, the above compounds 1-6 belong to C13 nor-sesquiterpenoids, sharing the same carbon skeleton of megastigmane. According to this study, they are one of major kinds of chemical constituents of Gynura nepalensis and have important reference value for the investigation on phytotaxonomy of this species.

Advance in studies on pharmacological activity of coptisine hydrochloride / 中国中药杂志

Coptisine hydrochloride, as a natural protoberberine alkaloid quaternary ammonium salt, can be found in many species of Ranunculaceae and Papaveraceae plants. Despite no in-depth studies on coptisine hydrochloride, some literatures have reported that coptisine hydrochloride has such pharmacological activities as inhibition of monoamine oxidase of type A, selective inhibition and double inhibition against vascular smooth muscle cell proliferation, inhibition of differentiation and function of osteoclasts, selective regulation of multidrug-resistant and drug-resistant proteins in vascular smooth muscle cells, anti-fungus, protection of gastric-mucous membrane, cytotoxicity, and myocardial protection. Given to the fact of the lack of systematic review and summary of studies on coptisine hydrochloride, we summarize and analyze the study literatures on the pharmacological activity of coptisine hydrochloride published in recent years, so as to provide information for studies on new drugs of coptisine hydrochloride on the basis of the pharmacological activity.

Biocompatibility of polyurethane-BaFe(12)O(19 ) composite microsphere as a new endovascular embolization material / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the biocompatibility of polyurethane-BaFe(12)O(19) magnetic composite microsphere as a new endovascular embolization material.</p><p><b>METHODS</b>The biocompatibility of BaFe(12)O(19) particle was evaluated in vitro using Ames test, cell toxicity test, acute and subacute systemic toxicity test, hemolysis test, bleeding time and clotting time test and blood clotting function assay.</p><p><b>RESULTS</b>Ames test showed that the MR values of this particle leaching solution were all less than 2 without mutagenicity. Cell toxicity test showed that leaching solution at different concentrations had grade I toxicity on L929 cells. Acute and subacute systemic toxicity test showed that the experimental animals had good general condition without obvious pathological abnormality. The hemolysis rate of experimental group was 2.43%, which met the ISO standard (no more than 5%). The bleeding time and clotting time in mice were comparable between the experimental group and control group (P>0.05). There were no significant differences in blood clotting function between experimental group and control group (P>0.05).</p><p><b>CONCLUSION</b>The material has no obvious toxicity or mutagenicity, and does not cause hemolysis or hemopexis or affect the bleeding time and clotting time. Polyurethane-BaFe(12)O( 19) particle possesses satisfactory biocompatibility.</p>

A new flavonoid from heartwood of Caesalpinia sappan / 中国中药杂志

<p><b>OBJECTIVE</b>To seek for new active components from Caesalpinia sappan.</p><p><b>METHOD</b>The chemical constituents were isolated and identified by means of chromatographic and spectroscopic technologies methods.</p><p><b>RESULT</b>Nine compounds were isolated, and their structures were identified as 3, 8-dihydroxy4, 10-dimethoxy-7-oxo-[2] benzopyrano[4,3-b] benzopyran (1), 3-deoxysappanchalcone (2), sappanchalcone (3), 3-deoxysappanone B (4), rhamnetin (5), protosappanin C (6), 3, 7-dihydroxy-chroman-4-one (7), dimethyl adipate (8), daucosterin (9).</p><p><b>CONCLUSION</b>Compound 1 was a new compound, and compounds 7, 8 were isolated from this plant for the first time.</p>

Chemical constituents from roots of Ferula sinkiangensis / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of the roots of Ferula sinkiangensis.</p><p><b>METHOD</b>Compounds were isolated by repeated chromatography on silica gel. Their structures were elucidated by chemical and spectroscopic methods.</p><p><b>RESULT</b>Seven compounds were identified as fekrynol (1), fekolone (2), farnesiferol B (3), isosamarcandin (4), episamarcandin (5), farnesiferol C (6), umbelliferone (7).</p><p><b>CONCLUSION</b>All the compounds were obtained from this plant for the first time.</p>

Studies on the system for the exclusive control substance in traditional Chinese herbal medicines / 中国中药杂志

<p><b>OBJECTIVE</b>To establish the system for the exclusive control substance of plant drug (CSPD) in traditional Chinese herbal medicines (TCHM) for the purpose of original identification.</p><p><b>METHOD</b>Three kinds of representative TCHMs were selected and their exclusive CSPDs were obtained by standardized procedure. The expression of the total chemical characteristic of the CSPDs were achieved with the comparative analysis of the 1H-NMR spectra for the CSPDs of the samples of the same species collected from different regions as well as the isolation and elucidation of the chemical constituents.</p><p><b>RESULT</b>The 1H-NMR spectra of the CSPDs for three kinds of representative TCHMs have highly characteristic features and reproducibility, and showed mainly the resonance signals of the characteristic constituents of each species. These 1H-NMR spectra were strictly correlative with the origin of the species.</p><p><b>CONCLUSION</b>By using the procedure of this paper, the exclusive CSPDs can be obtained for most of TCHMs, which have important significance and can be regarded as references in the original identification of TCHMs.</p>

New dimeric phthalide derivative from Angelica sinensis / 药学学报

<p><b>AIM</b>To study the chemical constituents of the roots of Angelica sinensis.</p><p><b>METHODS</b>Silica gel column chromatography was used to separate the chemical constituents. Their structures were elucidated by chemical and spectral analysis (IR, MS, 1D and 2D NMR, etc.).</p><p><b>RESULTS</b>Besides three known phthalide derivatives, one new dimeric phthalide derivative and a pair of epimer were isolated and their structures were identified as Z-3',8',3'a,7'a-tetrahydro-6,3',7,7'a-diligustilide-8'-one (1), Z,Z'-6,6',7,3'a-diligustilide (2) and the 8-epimer (3) of 2 on the basis of spectral data.</p><p><b>CONCLUSION</b>Compound 1 is a new dimeric phthalide derivative, and compound 3 was first reported from radix Angelica</p>

Studies on chemical constituents in Flos Sophorae Carbonisatus / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the chemical constituents in Flos Sophorae Carbonisatus.</p><p><b>METHOD</b>Silica gel column chromatography was used to separate and purify the chemical constituents. The structures were elucidated by spectral analysis.</p><p><b>RESULT</b>Six compounds were isolated from Flos Sophorae Carbionisatus, and their structures were elucidated as maltol (1), 3-hydroxypyridine (2), malto-3-O-[6'-O-(4"-hydroxy-tans-cinnamoyl)-beta-D-glucopyranoside (3), 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] sophoradiol ethyl ester (4), 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] sophoradiol methyl ester (5), rutin (6).</p><p><b>CONCLUSION</b>4 is a new compound, and 1,2,3,5 were first reported from Flos Sophorae Carbonisatus.</p>

The new secondary metabolite from Polygonatum odoratum / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the chemical constituents of Polygonatum odoratum.</p><p><b>METHOD</b>Silica gel column chromatography was used to separate and purify the chemical constituents. The structures were elucidated by chemical and spectral analysis.</p><p><b>RESULT</b>One dipeptide and one furostanol glycoside were isolated from the rhizomes of P. odoratum, and their structures were identified as O-acetate of N (N-benzoyl-S-phenylalaninyl)-S-phenylalaninol (1) and 22-hydroxy-25 (R and S)-furost-5-en-12-on-3beta,22,26-triol 26-O-beta-D-glucopyranoside (2), respectively.</p><p><b>CONCLUSION</b>Compound (2) is a new compound and is first reported to be of the furostanol monoglycoside glycosylated at C-26.</p>

Establishment of the control substance of plant drug and fingerprints of Coptis chinensis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To establish the control substance of plant drug (CSPD) of Coptis chinensis Franch. and its proton nuclear magnetic resonance (1H NMR) and high performance liquid chromatography (HPLC) fingerprints for the purpose of original identification.</p><p><b>METHODS</b>The CSPD and their 1H NMR and HPLC fingerprints of Coptis chinensis were obtained by standardized procedure. Chemical components were isolated from the CSPD by silica gel column chromatography. By elucidation of their structures, the assignments of the characteristic signals in fingerprints could be achieved. RESULTS; The 1H NMR and HPLC fingerprints of the samples from various sources had wonderful reproducibility and characteristic features. Furthermore, five main compounds were isolated from CSPD and their structures were authenticated by spectral analysis as palmatine chloride, berberine chloride, epiberberine chloride, coptisine chloride, and jatrorrhizine chloride, respectively. The 1H NMR and HPLC fingerprints of the CSPD of Coptis chinensis showed mainly the characteristic signals of the berberine-type compounds isolated in this work.</p><p><b>CONCLUSION</b>The 1H NMR and HPLC fingerprints of the CSPD of Coptis chinensis exhibit the structures and total composition of the main active constituents in it, and can be used for its original identification and quality evaluation.</p>

Analysis of 1H-NMR fingerprint in stem of Dendrobium loddigesii / 中国中药杂志

<p><b>OBJECTIVE</b>To analyse the 1H-NMR finger-print of the stem of Dendrobium loddigesii.</p><p><b>METHOD</b>Silica gel column chromatography was used to separate the chemical constituents of SCE A of the stem of D. loddigesii. The characteristic signals of the H-NMR finger-print were analysed after determining the structures of the compounds isolated from SCE A.</p><p><b>RESULT</b>1H-NMR finger-prints of the samples of D. loddigesii collected from different regions showed highly characteristic features and reproducibility. Four compounds predominant in SCE A were isolated and their structures were determined by spectral analysis as 1, 2, 3 and 4, respectively.</p><p><b>CONCLUSION</b>Compound 3 and 4 were isolated from D. loddigesii for the first time. The 1H-NMR finger-print of CGE A of the stem of D. loddigesii showed mainly the characteristic signals of the above four compounds and might be utilized for the original authentication of this plant.</p>