2-Benzoylbenzofuran derivatives possessing piperazine linker as anticancer agents.

A series of novel 2-benzoylbenzofuran derivatives possessing piperazine linker have been prepared, and their in vitro anticancer activity against a panel of human tumor cell lines by MTT assay were evaluated. The results demonstrated that tertiary amine derivatives exhibited better cytotoxic activity, and SAR study revealed that electron-donating substituents on the phenyl ring of the derivatization functionality contributed to potent anticancer activities. Among them, compounds 6, 9, 11, 18, 23 and 25 displayed both better anti-tumor activity and lower cytotoxic effect on human normal liver cell L02. Further apoptosis analysis showed that compound 18 significantly induced apoptosis in A549 cell, which was considered as the most potent anticancer agent.

Three new C-alkylated flavonoids from Desmodium oblongum.

Three new C-alkylated flavonoids, 4'-hydroxy-8-isobutyryl-7-methoxy-6-methyl-flavone (1), 4',7-dimethoxy-8-isobutyryl-6-methyl-flavone (2), and 4',7-dimethoxy-8-isobutyryl-flavone (3), together with three know ones luteolin (4), kaemferol (5), and quercetin (6), were isolated from Desmodium oblongum. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compound 1 showed cytotoxicity against NB4, SHSY5Y, and MCF7 cell lines with IC50 values of 8.5, 6.5, and 7.8 µM; compound 2 showed cytotoxicity against SHSY5Y and PC3 cell lines with IC50 values of 5.0 and 6.8 µM; compound 3 displayed cytotoxicity against SHSY5Y and MCF7 cell lines with IC50 values of 6.4 and 9.4 µM, respectively.

Design, synthesis and anticancer activity of novel hybrid compounds between benzofuran and N-aryl piperazine.

A series of novel hybrid compounds between benzofuran and N-aryl piperazine have been designed and prepared. These derivatives were evaluated for their in vitro anti-tumor activity against a panel of human tumor cell lines by MTT assay. The results demonstrated that amide derivatives were more bioactive than sulfonamide compounds in general, and that chloro or trifluoromethyl substituent was vital for modulating cytotoxic activity. In particular, compound 13 was found to be the most potent compound against 4 strains human tumor cell lines, and exhibited cytotoxic activity selectively against Hela (0.03µM).

[Study on Chemical Constituents of Peanut Hull].

OBJECTIVE: To investigate the chemical constituents of peanut hull. METHODS: Several chromatography methods such as silica gel and Sephadex LH-20 combined with recrystallization were applied to isolate the compounds. Based on spectrum technologies (MS,1H-NMR and 13C-NMR) and physico-chemical methods, structures of isolated compounds were identified. RESULTS: Twelve compounds were isolated and elucidated as luteolin (1), diosmetin (2), 5,7,3',4'-tetrahydroxy-8-prenyflavone (3),5,7,3'-trihydroxy-4'- methoxy-8-prenylflavone(4), eriodicrtyol (5), racemoflavone (6), hydnocarpin (7), 5,7-dihydroxy chromone (8), 5-hydroxy-chromone- 7-O-ß-D-glucoside (9), ferulic acid (10), ß-sitosterol (11) and daucosterol(12). CONCLUSION: Except compounds 1, 5 and 8, all compounds are obtained from peanut hull for the first time.

Limonoids from the fruits of Cipadessa cinerascens.

A new limonoid, 3-de(2-methylbutanoyl)-3-propanoylcipadesin (1), along with 10 known limonoids and 1 known triterpenoid, was isolated from the fruits of Cipadessa cinerascens. Their structures were elucidated on the basis of spectroscopic analysis. All compounds were evaluated for their antimicrobial activities, and compounds 6 and 12 showed weak antimicrobial activities against MRSA 82(#) and MRSA 92(#).

[Chemical constituents from aerial part of Aconitum brachypodum].

OBJECTIVE: To study the chemical constituents from the aerial part of Aconitum brachypodum. METHODS: The constituents were isolated and purified by silica gel, activated alumina and Sephadex LH-20 column chromatography. their structures were elucidated on the basis of spectral data and physiochemical evidence. RESULTS: Eleven compounds were isolated from 80% ethanol extract and identified as secokaraconitine (1), brachyaconitines A (2), C (3), talatisamine (4), hypaconitine (5), songrine (6), bullatine A (7), 7-carbony sitosterone (8), lupeol (9), ß-sitosterol (10) and daucosterol (11). CONCLUSION: All compounds are isolated from the aerial part of Aconitum brachypodum for the first time.

[Akaloids from roots of Stephania dentifolia].

Eight alkaloids were isolated from the thin sulfuric acid extracts of the fresh roots of Stephania dentifolia by aluminum oxide, silica and Sephadex LH-20 column chromatography methods. Based on the spectroscopic analysis and chemical evidence, the structures of these alkaloids were identified as sinoacutine (1), sinomenine (2), cephamonine (3), tetrahydropalmatine (4), capaurine (5), stepharanine (6), (+)-stepharine (7) and palmatine (8). All compounds were obtained from this plant for the first time.

[Chemical constituents of Aconitum brachypodum from Dong-Chuan area].

Aconitum brachypodum is traditionally known to be toxic chinese medicie, but its chemical constituents is not enough studied to date. To further elucidate the chemical constituents of A. brachypodum, 80% ethanol extract of A. brachypodum collected from Dong-Chuan area was investigated, which led to isolation of seventeen compounds. By spectroscopic methods, their structures were determined as hypaconitine (1), mesaconitine (2), talatisamine (3), neoline (4), fuziline (5), aconine (6), bullatine A (7), lepeine (8), songrine (9), isocorydine (10), beta-sitosterol (11), daucosterol (12), stearic acid (13), triacontanol (14), palmitic acid (15), benzoic acid (16), and inosine (17), respectively. All compounds except for compounds 1 and 7 were isolated from A. brachypodum for the first time.

Activity of Compound Agrimony Enteritis Capsules against invasive candidiasis: Exploring the differences between traditional Chinese medicine prescriptions and its main components in the treatment of diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Agrimony Enteritis Capsules (FFXHC) is an ethnomedicine derived from Yi Nationality Herbal Medicine for the treatment of enteritis. We found that compared to berberine hydrochloride (BBR), a component of this medicine, FFXHC was more efficacious in the mouse model of IC mice in significantly alleviating lung and intestinal lesions. " Our study provides a novel perspective into the pharmacological mechanism of action of the ethnic compound FFXHC. AIM OF THE STUDY: To determine the underlying mechanism of the superiority of FFXHC over BBR in IC. MATERIALS AND METHODS: The susceptibility of Candida albicans to FFXHC was evaluated in vitro. The mouse model of IC was established and the survival rate, weight change, the number of organ colonies, and immune organ coefficient of the mice were determined, the effect of FFXHC on the immune function of mice, including changes in the number of immune cells, levels of the related inflammatory cytokines (INF-γ, TNF-α, MCP-1, IL-6, and IL-17A), and the antimicrobial peptide, LL-37 (CRAMP in mice), were determined. Mice feces were collected and changes in the intestinal microecology were studied. RESULTS: Our findings indicated that FFXHC was not active against Candida albicans and did not restore the sensitivity of the resistant strain in vitro; however, it had a therapeutic effect that improve survival rate on mice with IC. The number of lymphocytes and neutrophils of mice with IC treated with FFXHC increased significantly. The intestinal microecology of mice was restored and the abundance of the probiotic Bacteroides was increased, which further stimulated the production of the antimicrobial peptide, LL-37, which is required for acquired immunity. Furthermore, the levels of Th cell-related cytokines, including INF-γ, TNF-α, and IL-17A were significantly increased, whereas those of the proinflammatory cytokines, IL-6 and MCP-1, decreased. With the activation of acquired immunity, the immune function of mice was restored, the body weight and survival rate of mice improved considerably, the coefficients of the thymus and spleen increased, and the number of fungal colonies in the lung and kidney decreased. CONCLUSIONS: FFXHC could eliminate fungi by increasing the relative abundance of probiotics in Bacteroides and the number of neutrophils, thereby promoting the production of CRAMP and resulting in a fungicidal effect, leading to acquired immunity. Although BBR has an antifungal effect, we found that it was not as effective as FFXHC.

Antifungal Activity and Potential Mechanism of 6,7, 4'-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans.

The increased resistance of Candida albicans to conventional antifungal drugs poses a huge challenge to the clinical treatment of this infection. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. This study assessed the effect of 6,7,4'-O-triacetylscutellarein (TA) combined with fluconazole (FLC) on C. albicans in vitro and in vivo. TA combined with FLC showed good synergistic antifungal activity against drug-resistant C. albicans in vitro, with a partial inhibitory concentration index (FICI) of 0.0188-0.1800. In addition, the time-kill curve confirmed the synergistic effect of TA and FLC. TA combined with FLC showed a strong synergistic inhibitory effect on the biofilm formation of resistant C. albicans. The combined antifungal efficacy of TA and FLC was evaluated in vivo in a mouse systemic fungal infection model. TA combined with FLC prolonged the survival rate of mice infected with drug-resistant C. albicans and reduced tissue invasion. TA combined with FLC also significantly inhibited the yeast-hypha conversion of C. albicans and significantly reduced the expression of RAS-cAMP-PKA signaling pathway-related genes (RAS1 and EFG1) and hyphal-related genes (HWP1 and ECE1). Furthermore, the mycelium growth on TA combined with the FLC group recovered after adding exogenous db-cAMP. Collectively, these results show that TA combined with FLC inhibits the formation of hyphae and biofilms through the RAS-cAMP-PKA signaling pathway, resulting in reduced infectivity and resistance of C. albicans. Therefore, this study provides a basis for the treatment of drug-resistant C. albicans infections.

[Studies on the chemical constituents of the leaves of Polygonum multiflorum].

OBJECTIVE: To study the chemical constituents of the leaves of Polygonum multiflorum. METHODS: The chemical constituents were extracted with water and separated by manifold chromatography technique, and their structures were determined by spectral analysis. RESULTS: Eleven compounds were isolated and identified as physcion (I), emodin (II), noreugenin (III), apigenin (IV), hyperoside (V), rutin (VI), vitexin (VII), 2,3,5 ,4'-tetrahydroxy-stibene-2-O-beta-D-glucoside (VIII), beta-amyrin (IX), beta-sitosterol (X), daucosterol( XI). CONCLUSION: Among these compounds, I - IV, VI - XI are isolated from the leaves of Polygonum multiflorum for the first time.

Synthesis and Biological Evaluation of New Piperazine Substituted 3, 5-Diarylisoxazolines.

AIM AND OBJECTIVE: Isoxazolines are an important class of nitrogen and oxygen-containing heterocycles, which have gained much importance as the potential biological agents. In order to study structureactivity relationships of isoxazolines, this work has been conducted. MATERIALS AND METHODS: A series of new piperazine substituted 3, 5-diarylisoxazoline derivatives (6-31) were designed and synthesized, and in vitro anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and anticancer effect against a panel of human tumor cell lines (Hela, A549 and SGC7901) by MTT assay were evaluated. RESULTS: The substituents of the NH group of piperazine ring had an obvious influence on biological activities. Especially, compounds 5, 7, 8, 10, 11, 13 and 27-showed good inhibitory effect on the generation of NO compared to dexamethasone. Furthermore, derivatives 5, 6, 7, 8, 9, 13 and 26 were found to be potential selectively anticancer activity on human tumor cell lines, which displayed better cytotoxic activity to positive control 5- FU. CONCLUSION: Piperazine substituted 3, 5-diarylisoxazoline derivatives could be considered as new antiinflammatory and anticancer agents.

[Studies on chemical constituents of Peucedanum delavayi].

OBJECTIVE: To study the chemical constituents of the radix and rhizome of Peucedanum delavayi. METHODS: The chemical constituents had been separated by manifold chromato-graphy methods, and their structures were determined by spectral analysis. RESULTS: Fifteen compounds were isolated and identified as Umbelliferone(I), Coumurayin(II), Mexoticin(III), Marmesin (IV), Ammijin(V), Delton (VI), Selinidin(VII), Anomalin(VII), Isopteryxin(IX), Ferulic acid(X), Falcarindiol(XI), Stearic acid(XII), beta-sitosterol(X III), Daucosterol(XIV) and d-Mannitol(XV). CONCLUSION: All these compounds are isolated from Peucedanum delavayi for the first time.

[Studies on chemical constituents from rattan of Polygonum multiflorum].

OBJECTIVE: To study on the chemical constituents from rattan of Polygonum multiflorum. METHODS: The chemical constituents were extracted with alcohol and were separated with manifold chromatography technique. Their structures were determined by spectral analysis. RESULTS: Thirteen compounds were isolated and identified as Chrysophanol(I), Physcion(II), Emodin(III), Aloeemodin(IV), Rhein(V), Physcion-8-O-beta-D-glucoside(VI), Emodin-8-O-beta-D-glucoside (VII),2,3,5,4'-Tetrahydroxy-stibene-2-O-beta-D-glucoside(VIII), Noreugenin(IX), Apigenin(X), Daucosterol(XI), beta-Sitosterol(XII), Stearic acid(XIII). CONCLUSION: Among these, compounds I, IV-VI, VIII-XI, XIII are isolated from rattan of Polygonum multiflorum for the first time.

[Studies on the chemical constituents of the aerial parts of Seseli mairei].

OBJECTIVE: To study the chemical constituents of the aerial parts of Seseli mairei Wolf. METHODS: The chemical constituents have been separated with manifold chromatography methods, and their structures were determined hy spectral analysis. RESULTS: Thirteen compounds were isolated and identified as sphondin (I), hergapten (II), isopimpinellin (III), umbelliferone (IV), chrysosptertin B (V), apiin (VI), rutin (VII), quercetin (VIII), ferulic acid (IX), falcarindiol (X), docosanol (XI), beta-sitosterol (XII), daucosterol (X III). CONCLUSION: All these compounds were isolated from the aerial parts of Seseli mairei Wolf. for the first time.

Development and validation of a LC-ESI-MS/MS method for the determination of swertiamarin in rat plasma and its application in pharmacokinetics.

A new LC-ESI-MS/MS assay method has been developed and validated for the quantification of swertiamarin, a representative bioactive substance of Swertia plants, in rat plasma using gentiopicroside, an analog of swertiamarin on chemical structure and chromatographic action, as the internal standard (IS). The swertiamarin and IS were extracted from rat plasma using solid-phase extraction (SPE) as the sample clean-up procedure, and they were chromatographed on a narrow internal diameter column (Agilent ZORBAX ECLIPSE XDB-C(18) 100 mm × 2.1 mm, 1.8 µm) with the mobile phase consisting of methanol and water containing 0.1% acetic acid (25:75, v/v) at a flow rate of 0.2 mL/min. The detection was performed on an Agilent G6410B tandem mass spectrometer by negative ion electrospray ionisation in multiple-reaction monitoring mode while monitoring the transitions of m/z 433 [M+CH(3)COO](-)→179 and m/z 415 [M+CH(3)COO](-)→179 for swertiamarin and IS, respectively. The lower limit of quantification (LLOQ) was 5 ng/mL within a linear range of 5-1000 ng/mL (n=7, r(2)≥0.994), and the limit of detection (LOD) was demonstrated as 1.25 ng/mL (S/N≥3). The method also afforded satisfactory results in terms of sensitivity, specificity, precision (intra- and inter-day), accuracy, recovery, freeze/thaw, long-time stability and dilution integrity. This method was successfully applied to determination of the pharmacokinetic properties of swertiamarin in rats after oral administration at a dose of 20 mg/kg. The following pharmacokinetic parameters were obtained (mean): maximum plasma concentration, 1920.1 ng/mL; time to reach maximum plasma concentration, 0.945 h; elimination half-time, 1.10h; apparent total clearance, 5.638 L/h/kg; and apparent volume of distribution, 9.637 L/kg.

Antifungal alkaloids from the fresh rattan stem of Fibraurea recisa Pierre.

AIM OF THE STUDY: The rattan stem of Fibraurea recisa Pierre. is known as an ethno-remedy commonly used for the treatment of various skin diseases by the minority Yao, Zhuang and Miao in Yunnan Province of China. The present study was designated to evaluate its antifungal activity, and to root out the antifungal substances from this ethical herb. MATERIALS AND METHODS: The in vitro antifungal assay was performed by agar diffusion test for extracts and fractions. Then, the active fractions were submitted to column chromatography on silica gel and LH-20 to isolate their compounds. And the antifungal activity of pure compounds has been examined by checkerboard microdilution test. Nine Candida strains and one Cryptococcus strain were used for the bioassay. RESULTS: The MeOH extract exhibited significant antifungal activity, and the alkaloidal fractions were deduced as main active component. Subsequent studies led to the identification of a new alkaloid fibrecisine (1) and 21 known alkaloids including berberines, tetrahydroberberines and aporphine derivatives. The bioassay result indicated that the berberines showed more potent activity than aporphine derivatives against the test Candida strains, while tetrahydroberberines showed very weak activity against Cryptococcus neoformans. CONCLUSION: The new alkaloid fibrecisine (1) was identified as 1,2-methylenedioxy-8-hydroxy-6a(R)-aporphine by detailed spectral analysis. The rattan stem of Fibraurea recisa Pierre. is an effective antifungal herb, and its major active component is alkaloidal compounds. Bioassay tests revealed that the water-soluble berberines are the most important antifungal substances. The study provides preliminary scientific validation for the traditional medicinal use of this ethno-remedy.