Fang Yan

China Pharmaceutical University, Nan-ching-hsü, Jiangxi Sheng, China

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Publications (16)45.42 Total impact

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    ABSTRACT: L-phenylalanine imprinting chiral ordered mesoporous silica (L-Phe-COMS) was facile synthesized in the presence of amino acid phenylalanine by combining tetraethyl orthosilicate and quaternized aminosilane silica sources. The obtained COMS was favoured with MCM-41-type structure, narrow pore size distribution, and high specific surface area characterized by powder X-ray diffraction and N2 adsorption experiments. The imprinting chirality of COMS was disclosed by mixed and separate L- and D- phenylalanine adsorption on the L-Phe-COMS with a stereoselective adsorption capacity up to 3.24. In addition, six racemic mixtures including amino acids and drugs were explored to test the stereoselective adsorption capacity of L-Phe-COMS. The imprinting chiral ordered mesoporous silica take advantages of straightforward synthesis approach and robust stereoselective adsorption capacity, making it a processing candidate for chiral adsorption and separation.
    RSC Advances 10/2014; 4(98). DOI:10.1039/C4RA11302K · 3.84 Impact Factor
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    ABSTRACT: Piperaquine, 1,3-bis-[4-(7-chloroquinolyl-4)-piperazinyl-1]-propane, is an anti-malarial compound belonging to the 4-aminoquinolines, which has received renewed interest in treatment of drug resistant falciparum malaria in artemisinin-based combination therapy with dihydroartemisinin. The impurity profile of this drug product is paid an ever-increasing attention. However, there were few published studies of the complete characterization of related products or impurities in piperaquine phosphate bulk and forced degradation samples. The impurities in piperaquine phosphate bulk drug substance were detected by a newly developed gradient phase HPLC method and identified by TOF-MS and ESI-MS. The structures of impurities were confirmed by NMR. Forced degradation studies were also performed for the stability of piperaquine phosphate bulk drug samples and the specificity of the newly developed HPLC method. In silico toxicological predictions for these piperaquine phosphate related impurities were made by Toxtree® and Derek®. Twelve impurities (imp-1–12) were detected and identified, of which eight impurities (imp-1, 2, 4, 6–10) were first proposed as new related substances. Based on TOF-MS/ESI-MS and NMR analysis, the structures of imp-2, 6 and 12 were characterized by their synthesis and preparation. The possible mechanisms for the formation of impurities were also discussed. These piperaquine phosphate related impurities were predicted to have a toxicity risk by Toxtree® and Derek®. From forced degradation and bulk samples of piperaquine phosphate, twelve compounds were detected and identified to be piperaquine phosphate related impurities. Two of the new piperaquine phosphate related substances, imp-2 and imp-6, were identified and characterized as 4-hydroxy-7-chloro-quinoline and a piperaquine oxygenate with a piperazine ring of nitrogen oxide in bulk drug and oxidation sample, respectively. The MS data of imp-1, 2, 4, 6–10 were first reported. The in-silico toxicological prediction showed a toxicity risk for piperaquine related impurities by Toxtree® and Derek®.
    Malaria Journal 10/2014; 13(1):401. DOI:10.1186/1475-2875-13-401 · 3.49 Impact Factor
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    ABSTRACT: Overexpression of P-glycoprotein leads to tumor multidrug resistance (MDR). HZ08, a novel tetrahydro-isoquinoline derivate, was discovered to inhibit the MDR in the cancer cell lines of MCF-7/ADM, K562/ADM and KBV in our previous studies. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometric method (UPLC-MS/MS) was developed and validated for determination of HZ08 in rat plasma and tissues after intravenous administration of HZ08 liposome injection at different doses. The analytes were extracted from plasma and tissues using protein precipitation by acetonitrile with clotrimazole as internal standard. The chromatographic separation was performed on a Thermo BDS HYPERSIL C18 column (100mm×4.6mm, 2.4μm) at a flow rate of 0.7ml/min using 0.2% ammonium acetate solution (containing 0.1% formic acid) and methanol as mobile phase. The total run time was 4min. The tandem mass detection was applied with electrospray ionization in positive ion selected reaction monitoring mode. The ion transitions monitored were m/z 523.5 to 342.3 for HZ08 and 277.1 to 165.1 for the internal standard, respectively. The calibration curves obtained were linear in different matrices, and the lower limit of quantification (LLOQ) achieved was 1ng/ml for rat plasma and 0.25ng/ml for rat tissues, respectively. The RSDs for intra- and inter-day precision were less than 15%. Extraction recovery, matrix effect and stability were satisfactory in rat plasma and tissues. The developed method was successfully applied to a pharmacokinetic study of HZ08 liposome injection following intravenous administration of 1, 3, 10mg/kg to Sprague-Dawley rats. The data profiles revealed that HZ08 had linear pharmacokinetic properties at the tested doses, and was rapidly distributed into the systemic circulation with wide distribution throughout the body followed by a rapid elimination phase. The major distribution tissues of HZ08 in rats were lung, spleen and liver. These results provided constructive contribution to support the clinical evaluation.
    Journal of Pharmaceutical and Biomedical Analysis 09/2014; 102C:246-252. DOI:10.1016/j.jpba.2014.09.017 · 2.83 Impact Factor
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    ABSTRACT: In this work, we firstly explored zeolitic imidazolate framework-8 (ZIF-8) as a novel adsorbent for selective adsorption of theophylline (TPE) over its structure-related analogs involving caffeine (CFE) and diprophylline (DPE) in aqueous solution in view of sole and mixed adsorption, desorption, and solid phase extraction. The adsorption kinetics of TPE on ZIF-8 obeyed pseudo-second-order kinetics. Analysis of the intraparticle diffusion plots revealed that more than one process affected the adsorption, and film (boundary layer) diffusion controlled the adsorption rate at the beginning. The adsorption isotherms of TPE on ZIF-8 followed the Freundlich model, and enthalpy rather than entropy controlled its adsorption. Evidence from FT-IR and X-ray photoelectron spectroscopic data showed that the adsorption of TPE was also driven by coordination of unsaturated zinc species in ZIF-8 with the carbonyl groups in TPE besides π–π interaction and molecular size. All these interactions made the ZIF-8 a promising candidate for the selective adsorption and extraction of structure-related analogs.
    RSC Advances 07/2014; 4(62). DOI:10.1039/C4RA05293E · 3.84 Impact Factor
  • Xiao Yan · Jin-Long Chen · Meng-Xiang Su · Fang Yan · Bo Li · Bin Di
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    ABSTRACT: While most research has focused on the development of carbon dot (CD) based fluorescence sensors, much less attention has been paid to the phosphorescence phenomenon and its potential applications to date. Herein, room temperature phosphorescence (RTP) of water soluble CDs free of deoxidants and other inducers was observed for the first time in pure aqueous solution. RTP of CDs could be significantly quenched when chelating with iron ions as well as aggregation of CDs, presumably resulting from the formation of non-luminescent chelate. Due to a high affinity of iron ions to phosphate ions through well-known Fe-O-P bonds, the quenched RTP of functionalized CDs by Fe3+ could be basically recovered in the presence of phosphate-containing molecules. For a proof-of-concept demonstration, adenosine-5′-triphosphate (ATP), as a common phosphate-containing metabolite was quantitatively detected by a phosphorescence “off-to-on” approach. The enhancement of RTP at 440 nm was linearly proportional to the concentrations of ATP ranging from 20 to 200 μM with a detection limit as low as 14 μM. Moreover, the iron ion engineered CDs based RTP probe was used to estimate ATP levels in human blood plasma.
    RSC Advances 01/2014; 4(43):22318. DOI:10.1039/c4ra02592j · 3.84 Impact Factor
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    ABSTRACT: Mesoporous organosilicas with both R-(+)-1,1'-binaphthyl-2,2'-diamine and ethane moieties bridging in the framework were synthesized. This mesoporous material was prepared via the one-step co-condensation of N,N'-bis-[(triethoxysilyl)propyl]-(R)-bis-(ureido)-binaphthyl (Si-DABN) with 1,2-bis(triethoxysilyl)ethane (BTSE) using octadecyltrimethylammonium chloride (C(18) TMACl) as a structural directing agent with the aid of a co-solvent (ethanol) in basic medium. The morphology of these bifunctionalized mesoporous organosilicas is sensitive to the Si-DABN mole fraction and the base concentration. And the mesostructure becomes less ordered as the mole fraction of Si-DABN in the initial mixture increases from 10 to 40%. Elemental analysis and Fourier transform infrared (FT-IR) spectrometer indicate that the binaphthyl diamine was successfully introduced to the mesoporous organosilicas. Acidic conditions are more suitable than basic ones for the hydrolysis and condensation of (R)-2,2'-dicyanomethoxy-6,6'-di[(2-triethoxysilyl)ethenyl]-1,1'-binaphthyl, a chiral silane precursors with a short silane side chain on the binaphthyl group. A column packed with these bifunctionalized mesoporous organosilica spheres exhibits greater selectivity for R/S-1,1'-bi-2,2'-naphthol than one packed with commercial SiO(2) grafted with N,N'-bis-[(triethoxysilyl)propyl]-(R)-bis-(ureido)-binaphthyl. Binaphthol and bromosubstituted binaphthol were fully resolved, but two ether derivatives were only partially enantioseparated and the other three ester derivatives were no fully resolved on the column via co-condensation method.
    Journal of Separation Science 08/2012; 35(15):1854-62. DOI:10.1002/jssc.201200047 · 2.59 Impact Factor
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    Fang Yan · Ying Hu · Bin Di · Ping Lei He · Guibin Sun
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    ABSTRACT: Indapamide, a non-thiazide antihypertensive diuretic agent, has been widely coadministered with other classes of antihypertensive agents to reach target systolic blood pressure. Indapamide is extensively metabolized by cytochromes P450. Interaction of indapamide and other antihypertensive drugs are unknown. We investigated the effects of other antihypertensive drugs on the metabolism and pharmacokinetics of indapamide in vitro and in vivo. Indapamide metabolism was studies in vitro using human liver microsomes pretreated with or without different concentrations of CYP-selective inhibitors and seven major antihypertensive drugs, felodipine, nifedipine, nitrendipine, telmisartan, irbesartan, valsartan and puerarin. Furthermore, the pharmacokinetics of indapamide was determined by HPLC-MS/MS to evaluate the effects of felodipine coadministered on the bioavailability of indapamide in rats in vivo. The Km and Vmax of indapamide metabolism were 114.35 ± 3.47 μM and 23.13 ± 6.61 μmol/g/min. The metabolites of indapamide, hydroxyl-indapamide and dehydrogen-indapamide, were followed. CYP3A4 and CYP2C19 were involved in indapamide metabolism in human live microsomes. In addition, felodipine, nifedipine and nitrendipine significantly inhibited indapamide metabolism with the maximum inhibitory rates of 82.6%, 72% and 95%, respectively. Felodipine significantly elevated indapamide plasma concentration and prolonged its half-life. Combination therapy of indapamide and felodipine might lead to the alteration of indapamide metabolism and pharmacokinetics. The consequence of such an interaction that may include increased effectiveness and side effect needs to be tudeis in human.
    Journal of Pharmacy and Pharmaceutical Sciences 01/2012; 15(2):208-20. · 1.68 Impact Factor
  • Lili Huang · Juan Lu · Bin Di · Fang Feng · Mengxiang Su · Fang Yan
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    ABSTRACT: Monodisperse spherical periodic mesoporous organosilicas (PMOs) with ethane integrated in the framework were synthesized and their application as stationary phase for chromatographic separation is demonstrated. The ethane-PMOs were prepared by condensation of 1,2-bis(triethoxysilyl)ethane (BTSE) in basic condition using octadecyltrimethylammonium chloride (C(18)TMACl) as template and ethanol as co-solvent. The morphology and mesoporous structure of ethane-PMOs were controlled under different concentrations of sodium hydroxide (NaOH) and EtOH. The results of scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (XRD), nitrogen sorption measurement, Fourier transform infrared spectroscopy (FT-IR) and elemental analysis showed that ethane-PMOs have spherical morphology, uniform particle distribution, highly ordered pore structure, high surface area and narrow pore-size distribution. The column packed with these materials exhibits good permeability, high chemical stability and good selectivity of mixtures of aromatic hydrocarbons in normal phase high-performance liquid chromatography (HPLC).
    Journal of Separation Science 09/2011; 34(18):2523-7. DOI:10.1002/jssc.201100103 · 2.59 Impact Factor
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    ABSTRACT: Tanshinone A is a novel derivative of phenanthrene-quinone extracted from Salvia miltiorrhiza BUNGE, a traditional herbal medicine. Cytotoxic effect of tanshinone A was observed in this study. Additionally its mechanism of promoting apoptosis was also investigated. MTT and SRB assays were applied to measure the effects of tanshinone A on the cell viability, the cell cycle distribution and cell apoptosis were measured by flow cytometry using PI staining and Annexin V/PI double staining method respectively. The changes of mitochondrial membrane potential were also detected by flow cytometry. Spectrophotometric method was used to detect the changes of caspase-3 activity. Western blotting assay was used to evaluate the expression of bcl-2, bax and c-Myc proteins. Results indicated that tanshinone A displayed a significant inhibitory effect on the growth of K562 cells in a dose- and time-dependent manner, and showed obvious minor damage to LO2 cells. Tanshinone A could arrest K562 cells in the G(0)/G(1) phase and induce apoptosis, decrease the mitochondrial transmembrane potential, decrease the expressions of bcl-2 and c-Myc proteins, increase the expression of bax protein and the activity of caspase-3. Accordingly, it was presumed that the apoptosis induction may be through the endogenous pathway. Subsequently, tanshinone A could be a promising candidate in the development of a novel antitumor agent.
    European journal of pharmacology 06/2011; 667(1-3):129-35. DOI:10.1016/j.ejphar.2011.06.004 · 2.68 Impact Factor
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    ABSTRACT: Ordered mesoporous silicas (OMSs) with spherical morphology were synthesized by using mixed surfactants of anionic sodium dodecyl sulfate and nonionic block copolymer EO20PO70EO20 (P123) as template through an acid-catalyzed silica sol–gel process. A variety of characterizations demonstrated that the silica products exhibited well-formed spherical morphology, ordered mesostructure, narrow pore size distribution and large surface area (~700m2g−1). It was found that the synthesized OMSs had high adsorption capacity by using oxymatrine as model solute. The column packed with the silica spheres exhibited low back pressure and baseline separation of aromatic compounds such as benzene and nitrobenzene could be achieved. These results demonstrated the synthesized OMSs as a potential stationary phase for liquid chromatography. KeywordsColumn liquid chromatography–Stationary phase–Ordered mesoporous silicas–Anionic surfactant
    Chromatographia 04/2011; 73(7):623-629. DOI:10.1007/s10337-011-1932-7 · 1.37 Impact Factor
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    ABSTRACT: A novel, sensitive and rapid liquid chromatographic-electrospray ionization mass spectrometric method was developed and validated for the determination of zofenopril and its active metabolite zofenoprilat in human plasma. The method was based on a single extraction step using methyl tert-butyl ether and did not require chemical derivatization. The chromatographic conditions were optimized; separation was performed on a phenyl-hexyl column (5μm, 250mm×4.6mm i.d.) with a mobile phase consisting of a solution of methanol and water (95:5, v/v) that also contained 0.1% of formic acid. A flow rate of 1.0mL/min was used. Zofenopril, zofenoprilat and the internal standard (IS) fosinopril sodium were measured using an electrospray ion source in a positive reaction monitoring mode. Linear calibration curves were generated for zofenopril concentrations between 0.1052 and 1052ng/mL and for zofenoprilat concentrations between 0.2508 and 2508ng/mL. In both cases, the coefficients of determination were greater than 0.995. The extraction recovery for zofenopril was 93.5% on average. It was 92.5% for zofenoprilat. The inter- and intra-batch precision and accuracy for both zofenopril and zofenoprilat were higher than 14%. The method was applied to measure the concentrations of zofenopril and zofenoprilat in plasma samples.
    Journal of pharmaceutical and biomedical analysis 02/2011; 55(3):527-32. DOI:10.1016/j.jpba.2011.02.010 · 2.83 Impact Factor
  • Chun Li · Bin Di · Weiqiang Hao · Fang Yan · Mengxiang Su
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    ABSTRACT: A synthetic approach for synthesizing spherical aminopropyl-functionalized ethane-bridged periodic mesoporous organosilicas (APEPMOs) is reported. The mesoporous material was prepared by a one-step co-condensation of 1,2-bis(triethoxysilyl)ethane (BTSE) and 3-aminopropyltriethoxysilane (APTES) using cetyltrimethylammonium chlorine (C(18)TACl) as a template with the aid of a co-solvent (methanol) in basic medium. The APEPMOs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), powder X-ray diffraction (XRD), nitrogen sorption measurement, Fourier transform infrared spectroscopy (FT-IR) and elemental analysis. It was shown that this material exhibited spherical morphology, ordered cubic mesostructure and good mechanical strength. The APEPMOs were tested as a potential stationary phase for liquid chromatography (LC) because the column exhibited reduced back pressure. Moreover, they exhibited good chemical stability in basic mobile phase, which can be ascribed to the ethane groups in the mesoporous framework.
    Journal of Chromatography A 01/2011; 1218(3):408-15. DOI:10.1016/j.chroma.2010.11.048 · 4.26 Impact Factor
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    ABSTRACT: A rapid, sensitive, and specific liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) method was developed and validated for simultaneous determination of aconitine (AC), mesaconitine (MA), and hypaconitine (HA), the three toxic constituents from Sini decoction (SND) in rat plasma. After the addition of citalopram as the internal standard (IS), plasma samples were basified with 100 microL 10% ammonium hydroxide, and then extracted with 1 mL ethyl acetate. Chromatographic separation was performed on a CN column (250 mm x 4.6 mm, 5 microm) with a mobile phase of methanol/40 mM ammonium acetate/formic acid (950:45:5, v/v/v) at the flow rate of 1.0 mL/min. Analytes were determined in a triple-quadrupole mass spectrometer in the selected reaction-monitoring (SRM) mode using electrospray source with positive mode. The method was validated over the concentration ranges of 0.01-10 ng/mL for AC, MA, and HA. The variation coefficients were always < 15% for both intraday and interday precision for each analyte. Mean accuracies were also within +/-15%. The method was proved to be sensitive, rapid, specific, accurate, and reproducible. It has been successfully applied to the pharmacokinetics study on rats after oral administration of SND.
    Journal of analytical toxicology 11/2009; 33(9):588-94. DOI:10.1093/jat/33.9.588 · 2.63 Impact Factor
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    ABSTRACT: The goal of this study was to estimate the blood brain barrier (BBB) permeability of Ginkgolide B in normal condition and models of ischemia both in vivo and in vitro. A sensitive LC-MS/MS analytical method was developed to determinate accurately the concentration of Ginkgolide B in cell, plasma and brain tissue. The injured rat brain microvessel endothelial cells (RBMECs) induced by Na(2)S(2)O(4) served as a hypoxia/reoxygenation model in vitro. Intracellular concentration of Ginkgolide B increased in injured cells in a concentration-dependent manner. As a model of in vivo-ischemia/reperfusion, we performed middle cerebral artery occlusion (MCAO) in rats. Concentration of Ginkgolide B in the brain tissues showed higher in cerebral ischemia-reperfused animals than that in normal rats. To evaluate potential clinical effect of Ginkgolide B, we determined therapeutic time window in MCAO rats. Up to i.v. administration at 2h after reperfusion of rats, Ginkgolide B could decrease infarction volume and brain edema, exerting significant protective effect in cerebral ischemia injury. In conclusion, Ginkgolide B could pass through BBB, especially after ischemia-reperfusion injury of brain, and might be therapeutically effective for ischemia/reperfusion injury of human brain.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 10/2009; 39(1-3):8-14. DOI:10.1016/j.ejps.2009.10.002 · 3.01 Impact Factor
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    ABSTRACT: Overexpression of P-glycoprotein (Pgp) and multidrug resistance protein 1 (MRP1) by tumors results in multidrug resistance (MDR) to structurally unrelated anti-tumor agents. HZ08, a chiral compound, was a newly synthesized tetraisohydroquinoline derivative to reverse Pgp and MRP1 mediated MDR. In present studies, R, S-HZ08 and their racemate reversed the resistance to adriamycin and vincristine of adriamycin-selected human leukemia (K562/ADM) cells that overexpress Pgp. R, S-HZ08 and their racemate modulated adriamycin cytotoxicity when R, S-HZ08 and their racemate were removed 12 h prior to the cytotoxicity assay. In addition, R, S-HZ08 and their racemate increased intracellular accumulation of Rhodamine123 in Caco-2 cells that overexpress Pgp. Furthermore, using a DNA content analysis and an annexin V binding assay, R, S-HZ08 and their racemate effectively reversed the resistance to adriamycin-induced apoptosis in K562/ADM cells. R, S-HZ08 and their racemate also moderately reversed the resistance to adriamycin and vincristine of MCF-7/ADM cells that overexpress MRP1. However, R, S-HZ08 and their racemate hardly affected intracellular glutathione (GSH) levels and glutathione S-transferase (GST) activities in MCF-7/ADM cells. The result showed that R, S-HZ08 and their racemate possibly reverse MDR1 mediated multidrug resistance by a direct interaction with MRP1, not interaction with MRP1 via GSH. Thus, R, S-HZ08 and their racemate should be useful for treating patients with tumors that overexpress both Pgp and MRP1.
    Biological & Pharmaceutical Bulletin 06/2008; 31(6):1258-64. DOI:10.1248/bpb.31.1258 · 1.78 Impact Factor
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    ABSTRACT: P-glycoprotein (P-gp) mediated multidrug resistance (MDR) is one of the main obstacles in tumour chemotherapy. A promising approach to reverse MDR is the combined use of nontoxic and potent P-gp inhibitor with conventional anticancer drugs. We have examined the potential of a newly synthesized tetrahydroisoquinoline derivative B3 as a MDR-reversing agent. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to examine the effect of B3 on the cytotoxicity in K562/A02 and MCF-7/ADM cells caused by doxorubicin (adriamycin). Accumulation and efflux of P-gp substrate rhodamine123 in K562/A02 and primary cultured rat brain microvessel endothelial cells (RBMECs) were measured to evaluate the inhibitory effect of B3 on P-gp. The K562/A02 xenograft model in nude mice was established to examine MDR-reversing efficacy of B3 in-vivo. The results indicated that co-administration of B3 resulted in an increase on chemosensitivity of K562/A02 and MCF-7/ADM cells to doxorubicin in a dose-dependent manner. Rhodamine123 accumulation in K562/A02 cells and RBMECs were significantly enhanced after the incubation with various concentrations of B3. Furthermore, B3 inhibited the efflux of rhodamine123 from RBMECs. Co-administration of B3 with doxorubicin significantly decreased weight and volume of tumour in nude mice. In conclusion, B3 is a novel and potent MDR reversal agent with the potential to be an adjunctive agent for tumour chemotherapy.
    Journal of Pharmacy and Pharmacology 01/2008; 59(12):1649-55. DOI:10.1211/jpp.59.12.0006 · 2.16 Impact Factor