WorldWideScience

Sample records for acridones

  1. Bioactive acridone alkaloids from Swinglea glutinosa.

    Science.gov (United States)

    Weniger, B; Um, B H; Valentin, A; Estrada, A; Lobstein, A; Anton, R; Maillé, M; Sauvain, M

    2001-09-01

    A new prenylated acridone alkaloid, 1,3,5-trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone (1), was isolated from the stembark of Swinglea glutinosa, along with three known acridone alkaloids, 5-hydroxynoracronycine (2), 1,3,5-trihydroxy-4-methoxy-2-(3-methylbut-2-enyl)-10-methyl-9-acridone (3), and 1,3,5-trihydroxy-4-methoxy-10-methylacridone (4). The isolated alkaloids were assessed in vitro against chloroquine-sensitive and -resistant Plasmodium falciparum strains and for cytotoxicity using HeLa cells. PMID:11575960

  2. Reactivity of allenylphosphonates and allenylphosphine oxides toward 9-chloroacridines and acridone- A facile route to new -substituted acridones

    Indian Academy of Sciences (India)

    A Leela Siva Kumari; Venu Srinivas; K C Kumara Swamy

    2013-11-01

    Base-mediated addition of acridones to allenylphosphonates/allenylphosphine oxides (OCH2CMe2CH2O)P(O)CH=C=CR1R2 {R1 = R2 = Me (1), R1 = R2 = [−CH2−]5 (2)}, Ph2P(O)C(H)=C=CR1R2 {R1 = R2 = Me (3), R1 = R2 = [−CH2−]5 (4)} and (EtO)2P(O)C(H)=C=CMe2 (5) in DMF results in the regiospecific formation of phosphono-acridones and acridonylphosphine oxides. The acridone addition products were also obtained in the reaction of allenes 1 and 2 with 9-chloroacridine under [Pd]-catalysed conditions, along with (unexpected) -acridinyl substituted allenes. In contrast, 9-benzyl-6-chloro-purine reacted with 1 affording a -substituted purinone phosphonate. Allenes 1-2 did not react with acridones in the absence of base (CsF), but in the presence of Pd(OAc)2/DMF (or DMA)/pivalic acid rearranged to give 1,3-butadienes probably via [Pd]-allyl complexes. The phosphono-acridones were amenable to Horner-Wadsworth-Emmons (HWE) reaction and led to -substituted acridones. Key products have been characterized by single-crystal X-ray crystallography.

  3. New acridone from the wood of Citrus reticulata Blanco.

    Science.gov (United States)

    Phetkul, Uraiwan; Wanlaso, Nutthakran; Mahabusarakam, Wilawan; Phongpaichit, Souwalak; Carroll, Anthony R

    2013-10-01

    A new acridone, named citruscridone (1) together with five known compounds were isolated from the wood of Citrus reticulata Blanco. Their structures were established based on spectroscopic evidence. The antibacterial and antifungal activities of the wood extracts and pure compounds were evaluated. PMID:23697332

  4. Antileishmanial and antifungal acridone derivatives from the roots of Thamnosma rhodesica.

    Science.gov (United States)

    Ahua, Kouassi Maximin; Ioset, Jean-Robert; Ransijn, Adriana; Mauël, Jacques; Mavi, Steven; Hostettmann, Kurt

    2004-04-01

    Eight furanocoumarins, one coumarin and four acridone derivatives have been identified in the roots of Thamnosma rhodesica (Rutaceae). Rhodesiacridone, one of these acridone derivatives, is reported here for the first time. Its structure was elucidated by spectrometric methods including ESI-HR, EI, DCI mass spectrometry, 1H, 13C and 2D NMR experiments. This novel compound showed activities against the intracellular form of a human pathogen, the protozoan parasite Leishmania major. Two known acridone related compounds, gravacridonediol and 1-hydroxy-10-methylacridone, exhibited activities against the intracellular form of the same parasite and the fungus Cladosporium cucumerinum, respectively. PMID:15081302

  5. Antiparasitic activities of acridone alkaloids from Swinglea glutinosa (Bl.) Merr

    International Nuclear Information System (INIS)

    Eleven acridone alkaloids isolated from Swinglea glutinosa (Bl.) Merr. were examined for in vitro activity against chloroquine-sensitive Plasmodium falciparum 3D7, Trypanosoma brucei rhodesiense STIB900 and Leishmania donovani L82. An assay with KB cells was developed in order to compare in vitro toxicity of alkaloids with the selective action on the parasites. Nine of the compounds had IC50 values ranging from 0.3 to 11.6 μM against P. falciparum. In contrast, a small number of compounds showed significant activity against T. brucei rhodesiense and none had activity against L. donovani. Among the alkaloids three had IC50 50 < 10 μM. The characterization of the acridone alkaloids, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9 (10H)-one (1), 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxypropan-2-yl)-11-methoxy-10-methylfuro [3,2-b] acridin-5(10H)-one (2) and 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2Hpyrano[ 2,3-a]acridin-12(7H)-one (3), is discussed, as well as the structure-activity relationship of all compounds assayed. Isolation and spectral data of alkaloids 1-3 are described for the first time although their cytotoxicities to cancer cells have been described before. (author)

  6. Acridone alkaloids as potent inhibitors of cathepsin V.

    Science.gov (United States)

    Severino, Richele P; Guido, Rafael V C; Marques, Emerson F; Brömme, Dieter; da Silva, M Fátima das G F; Fernandes, João B; Andricopulo, Adriano D; Vieira, Paulo C

    2011-02-15

    Cathepsin V is a lysosomal cysteine peptidase highly expressed in thymus, testis and corneal epithelium. Eleven acridone alkaloids were isolated from Swinglea glutinosa (Bl.) Merr. (Rutaceae), with eight of them being identified as potent and reversible inhibitors of cathepsin V (IC(50) values ranging from 1.2 to 3.9 μM). Detailed mechanistic characterization of the effects of these compounds on the cathepsin V-catalyzed reaction showed clear competitive inhibition with respect to substrate, with dissociation constants (K(i)) in the low micromolar range (2, K(i)=1.2 μM; 6, K(i)=1.0 μM; 7, K(i)=0.2 μM; and 11, K(i)=1.7 μM). Molecular modeling studies provided important insight into the structural basis for binding affinity and enzyme inhibition. Experimental and computational approaches, including biological evaluation, mode of action assessment and modeling studies were successfully employed in the discovery of a small series of acridone alkaloid derivatives as competitive inhibitors of catV. The most potent inhibitor (7) has a K(i) value of 200 nM. PMID:21277783

  7. Antiparasitic activities of acridone alkaloids from Swinglea glutinosa (Bl.) Merr

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Djalma A.P. dos; Vieira, Paulo C.; Silva, M. Fatima das G.F. da; Fernandes, Joao B. [Universidade Federal de Sao Carlos, SP (Brazil). Dept. de Quimica; Rattray, Lauren; Croft, Simon L. [London School of Hygiene and Tropical Medicine, London (United Kingdom). Dept. of Infectious and Tropical Diseases

    2009-07-01

    Eleven acridone alkaloids isolated from Swinglea glutinosa (Bl.) Merr. were examined for in vitro activity against chloroquine-sensitive Plasmodium falciparum 3D7, Trypanosoma brucei rhodesiense STIB900 and Leishmania donovani L82. An assay with KB cells was developed in order to compare in vitro toxicity of alkaloids with the selective action on the parasites. Nine of the compounds had IC{sub 50} values ranging from 0.3 to 11.6 {mu}M against P. falciparum. In contrast, a small number of compounds showed significant activity against T. brucei rhodesiense and none had activity against L. donovani. Among the alkaloids three had IC{sub 50} < 1.0 {mu}M against P. falciparum, whereas against T. b. rhodesiense five had IC{sub 50} < 10 {mu}M. The characterization of the acridone alkaloids, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9 (10H)-one (1), 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxypropan-2-yl)-11-methoxy-10-methylfuro [3,2-b] acridin-5(10H)-one (2) and 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2Hpyrano[ 2,3-a]acridin-12(7H)-one (3), is discussed, as well as the structure-activity relationship of all compounds assayed. Isolation and spectral data of alkaloids 1-3 are described for the first time although their cytotoxicities to cancer cells have been described before. (author)

  8. Specific accumulation and revised structures of acridone alkaloid glucosides in the tips of transformed roots of Ruta graveolens.

    Science.gov (United States)

    Kuzovkina, Inna; Al'terman, Irina; Schneider, Bernd

    2004-04-01

    The root tips of Ruta graveolens (common rue) show strong autofluorescence of acridone alkaloids, which are characteristic secondary metabolites of this plant. To study the specific distribution and accumulation of acridone alkaloids in various root segments of Ruta graveolens, root material was harvested from genetically transformed root cultures and extracts were investigated by chromatographic techniques and HPLC-(1)H NMR spectroscopy. The cells of the elongation and differentiation zones contained acridone glucosides and large amounts of acridone alkaloids, mainly rutacridone. Gravacridondiol glucoside was identified as the dominant secondary compound of the root tips and its structure revised by means of spectroscopic methods. In addition, minor acridones, including the structurally revised gravacridontriol glucoside and unknown natural products, were found in the root tip.

  9. Synthesis of a Fluorescent Acridone Using a Grignard Addition, Oxidation, and Nucleophilic Aromatic Substitution Reaction Sequence

    Science.gov (United States)

    Goodrich, Samuel; Patel, Miloni; Woydziak, Zachary R.

    2015-01-01

    A three-pot synthesis oriented for an undergraduate organic chemistry laboratory was developed to construct a fluorescent acridone molecule. This laboratory experiment utilizes Grignard addition to an aldehyde, alcohol oxidation, and iterative nucleophilic aromatic substitution steps to produce the final product. Each of the intermediates and the…

  10. Crystallization and preliminary crystallographic analysis of an acridone-producing novel multifunctional type III polyketide synthase from Huperzia serrata

    International Nuclear Information System (INIS)

    An acridone-producing novel type III polyketide synthase from H. serrata has been overexpressed in E. coli, purified and crystallized. Diffraction data have been collected to 2.0 Å. Polyketide synthase 1 (PKS1) from Huperzia serrata is a plant-specific type III polyketide synthase that shows an unusually versatile catalytic potential, producing various aromatic tetraketides, including chalcones, benzophenones, phlorogulucinols and acridones. Recombinant H. serrata PKS1 expressed in Escherichia coli was crystallized using the hanging-drop vapour-diffusion method. The crystals belonged to space group I222 or I212121, with unit-cell parameters a = 73.3, b = 85.0, c = 137.7 Å, α = β = γ = 90.0°. Diffraction data were collected to 2.0 Å resolution using synchrotron radiation at BL24XU of SPring-8

  11. Synthesis and antitumor activity of conjugates of muramyldipeptide or normuramyldipeptide with hydroxyacridine/acridone derivatives.

    Science.gov (United States)

    Dzierzbicka, Krystyna; Kołodziejczyk, Aleksander M

    2003-01-01

    A series of MDP (muramyldipeptide) or nor-MDP (normuramyldipeptide) analogues modified at the C-terminus post of the molecule by a formation of an ester bond between the carboxylic group of isoglutamine and the hydroxyl function of the respective derivatives of 4-carboxamide-acridine/9-acridone or 1-nitro-9-hydroxyalkylaminoacridines were synthesized as potential anticancer agents. The compounds O-(1-O-benzyl-N-acetyl-muramyl-l-alanyl-d-gamma-isoglutaminyl)-9-(ethylamino)-1-nitroacridine ester 3j and O-(1-O-benzyl-N-acetyl-muramyl-l-alanyl-d-gamma-isoglutaminyl)-9-propylamino-1-nitroacridine ester 3k exhibited high in vitro cytotoxic activity against a panel of human cell lines, prostate cancer and AIDS-related lymphoma (ARL). Analogue 3j was also active in vivo in the hollow fiber assay. Antitumor activity of both compounds were tested in vivo against difference human tumor xenograft, but only analogue 3k showed in vivo activity against sc UACC-62 melanoma in mice.

  12. Acridone Alkaloids from Swinglea glutinosa (Rutaceae) and Their Effects on Photosynthesis.

    Science.gov (United States)

    Arato Ferreira, Pedro H; Dos Santos, Djalma A P; da Silva, Maria Fátima das G F; Vieira, Paulo C; King-Diaz, Beatriz; Lotina-Hennsen, Blas; Veiga, Thiago A M

    2016-01-01

    Continuing our search for herbicide models based on natural products, we investigated the action mechanisms of five alkaloids isolated from Swinglea glutinosa (Rutaceae): Citrusinine-I (1), glycocitrine-IV (2), 1,3,5-trihydroxy-10-methyl- 2,8-bis(3-methylbut-2-en-1-yl)-9(10H)-acridinone (3), (2R)-2-tert-butyl-3,10-dihydro-4,9-dihydroxy-11-methoxy-10-methylfuro[3,2-b]acridin-5(2H)-one (4), and (3R)-2,3,4,7-tetrahydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-12H-pyrano[2,3-a]acridin-12-one (5) on several photosynthetic activities in an attempt to find new compounds that affect photosynthesis. Through polarographic techniques, the compounds inhibited the non-cyclic electron transport in the basal, phosphorylating, and uncoupled conditions from H2 O to methylviologen (=MV). Therefore, they act as Hill reaction inhibitors. This approach still suggested that the compounds 4 and 5 had their interaction site located at photosystem I. Studies on fluorescence of chlorophyll a suggested that acridones (1-3) have different modes of interaction and inhibition sites on the photosystem II electron transport chain. PMID:26765357

  13. Acridone derivative 8a induces oxidative stress-mediated apoptosis in CCRF-CEM leukemia cells: application of metabolomics in mechanistic studies of antitumor agents.

    Directory of Open Access Journals (Sweden)

    Yini Wang

    Full Text Available A new acridone derivative, 2-aminoacetamido-10-(3, 5-dimethoxy-benzyl-9(10H-acridone hydrochloride (named 8a synthesized in our lab shows potent antitumor activity, but the mechanism of action remains unclear. Herein, we report the use of an UPLC/Q-TOF MS metabolomic approach to study the effects of three compounds with structures optimized step-by-step, 9(10H-acridone (A, 10-(3,5-dimethoxybenzyl-9(10H-acridone (I, and 8a, on CCRF-CEM leukemia cells and to shed new light on the probable antitumor mechanism of 8a. Acquired data were processed by principal component analysis (PCA and orthogonal partial least squares discriminant analysis (OPLS-DA to identify potential biomarkers. Comparing 8a-treated CCRF-CEM leukemia cells with vehicle control (DMSO, 23 distinct metabolites involved in five metabolic pathways were identified. Metabolites from glutathione (GSH and glycerophospholipid metabolism were investigated in detail, and results showed that GSH level and the reduced/oxidized glutathione (GSH/GSSG ratio were significantly decreased in 8a-treated cells, while L-cysteinyl-glycine (L-Cys-Gly and glutamate were greatly increased. In glycerophospholipid metabolism, cell membrane components phosphatidylcholines (PCs were decreased in 8a-treated cells, while the oxidative products lysophosphatidylcholines (LPCs were significantly increased. We further found that in 8a-treated cells, the reactive oxygen species (ROS and lipid peroxidation product malondialdehyde (MDA were notably increased, accompanied with decrease of mitochondrial transmembrane potential, release of cytochrome C and activation of caspase-3. Taken together our results suggest that the acridone derivative 8a induces oxidative stress-mediated apoptosis in CCRF-CEM leukemia cells. The UPLC/Q-TOF MS based metabolomic approach provides novel insights into the mechanistic studies of antitumor drugs from a point distinct from traditional biological investigations.

  14. In vitro cytotoxicity activity on several cancer cell lines of acridone alkaloids and N-phenylethyl-benzamide derivatives from Swinglea glutinosa (Bl.) Merr.

    Science.gov (United States)

    Braga, P A C; Dos Santos, D A P; Da Silva, M F D G F; Vieira, P C; Fernandes, J B; Houghton, P J; Fang, R

    2007-01-01

    The methanol extract from the stems and fruits of Swinglea glutinosa (Rutaceae) afforded 11 known acridone alkaloids and three N-phenylethyl-benzamide derivatives, glycocitrine-IV, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9(10H)-one, 1,3,5- trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone, citbrasine, citrusinine-II, citrusinine-I, 5-dihydroxyacronycine, pyranofoline, 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2H-pyrano[2,3-a]acridin-12(7H)-one, 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxy-propan-2-yl)-11-methoxy-10-methylfuro[3,2-b]acridin-5(10H)-one, bis-5-hydroxyacronycine, N-(2-{4-[(3,7-dimethylocta-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, N-(2-{4-[(3,7-dimethyl-4-acethyl-octa-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, and severine acetate. All compounds isolated were examined for their activity against three cancer cell lines: human lung carcinoma (COR-L23), human breast adenocarcinoma (MCF7), human melanoma (C32), and normal human fetal lung cell line, MRC-5. The acridones tested exhibited weak cytotoxicity but the amides showed moderate nonselective cytotoxic activity. PMID:17365689

  15. Exposure of CCRF-CEM cells to acridone derivative 8a triggers tumor death via multiple mechanisms.

    Science.gov (United States)

    Wang, Yini; Gao, Dan; Chu, Bizhu; Gao, Chunmei; Cao, Deliang; Liu, Hongxia; Jiang, Yuyang

    2016-04-01

    A newly synthesized acridone derivative 8a shows potent antitumor activity against CCRF-CEM leukemia cells. Herein, the first proteomic study of 8a effects in CCRF-CEM cells was performed by 2D nano-LC-ESI-MS/MS to better understand the mechanisms of action of 8a. Data analyses based on PLGS, STRING, Cytoscape, and database for annotation, visualization, and integrated discovery identified 55 proteins that were differentially expressed in response to 8a exposure. Multiple cellular pathways were affected, including chromatin organization, energy metabolism, DNA repair, oxidative-stress, and apoptosis. The changes in protein expression were further verified for PKM2. Moreover, 8a lowered down the expression of HEX and PFK-1. Lactate production was decreased in 8a-treated cells, indicating suppression of glycolysis. The elevated XRCC6 and decreased histone expression levels suggested increased DNA damage in 8a-treated cells, which was confirmed by the increased γ-H2AX foci. Molecular docking of 8a with DNA demonstrated direct interactions of 8a with DNA through three hydrogen bonds and four π-π interactions, potentially explaining the mode of action that 8a damaged to DNA. The differential protein profiling and dysfunction of metabolic pathways induced by 8a provide novel insights into the potential action mechanisms of 8a.

  16. Novel acridone-modified MCM-41 type silica: Synthesis, characterization and fluorescence tuning

    Directory of Open Access Journals (Sweden)

    Maximilian Hemgesberg

    2011-06-01

    Full Text Available A Mobil Composition of Matter (MCM-41 type mesoporous silica material containing N-propylacridone groups has been successfully prepared by co-condensation of an appropriate organic precursor with tetraethyl orthosilicate (TEOS under alkaline sol–gel conditions. The resulting material was fully characterized by means of X-ray diffraction (XRD, N2-adsorption–desorption, transmission electron microscopy (TEM, IR and UV–vis spectroscopy, as well as 29Si and 13C CP-MAS NMR techniques. The material features a high inner surface area and a highly ordered two-dimensional hexagonal pore structure. The fluorescence properties of the organic chromophore can be tuned via complexation of its carbonyl group with scandium triflate, which makes the material a good candidate for solid state sensors and optics. The successful synthesis of highly ordered MCM materials through co-condensation was found to be dependent on the chemical interaction of the different precursors.

  17. Fate of Carbamazepine during Water Treatment

    DEFF Research Database (Denmark)

    Kosjek, T.; Andersen, Henrik Rasmus; Kompare, Boris;

    2009-01-01

    of acridone, hydroxy-(9H,10H)-acridine-9-carbaldehyde, acridone-N-carbaldehyde, and 1-(2-benzaldehyde)-(1H,3H-quinazoline-2,4-dione, while biological breakdown of acridine yielded acridone. In parallel, the transformation product iminostilbene was observed during sample analysis. In addition,this study...

  18. Phytochemical and chemosystematic studies of Conchocarpus marginatus and C. inopinatus (Rutaceae); Fitoquimica e quimiossistematica de Conchocarpus marginatus e C. inopinatus (Rutaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Bellete, Barbara Sayuri; Sa, Israel Civico Gil de; Mafezoli, Jair; Cerqueira, Cristovam do Nascimento; Silva, Maria Fatima das Gracas Fernandes da; Fernandes, Joao Batista; Vieira, Paulo Cezar; Zukerman-Schpector, Julio [Universidade Federal de Sao Carlos (UFSCAR), SP (Brazil). Dept. de Quimica; Pirani, Jose Rubens, E-mail: dmfs@ufscar.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Inst. de Biociencias

    2012-07-01

    Phytochemical studies of the leaves and stem have led to the identification of the known acridone alkaloids arborinine, methylarborinine, 1-hydroxy-3-methoxy-N-methyl acridone, xanthoxoline, 1,2,3,5-tetramethoxy-N-methylacridone, toddaliopsin C and the new seco acridone alkaloid inopinatin. The known quinoline alkaloids 2-phenyl-1-methyl-quinolin-4(1H)-one, 2-phenyl-1-methyl-7-methoxy-quinolin-4(1H)-one, dictamnine, and the coumarins scopoletin and marmesin were also isolated. The isolated compounds and the distribution of secondary metabolites, which are systematically important, obtained from literature, clearly confirmed that some species formerly described in the genera Angostura and Galipea in fact shall belong to the genus Conchocarpus. (author)

  19. ALCALOIDES ACRIDÔNICOS INIBEM CATEPSINA L E V

    Directory of Open Access Journals (Sweden)

    Emerson F. Marques

    2016-01-01

    Full Text Available Cathepsins represent a class of enzymes that has the primary function of randomly degrading proteins in the lysosomes, although are also involved in different pathologies. The aim of this paper was to evaluate the capacity of acridone alkaloids isolated from Swinglea glutinosa (Rutaceae to inhibit cathepsin L in vitro . The IC50 values found were in the 0.8-57 µM range and the most promising compounds were alkaloids 1 and 2, with IC50 of 0.9 and 0.8 µM, respectively. Enzyme kinetics revealed that they are reversible competitive inhibitors with respect to the substrate Z-FR-MCA. This small series of acridone alkaloids showed low selectivity for both cathepsins, but represent promising lead candidates for the further development of competitive cathepsin L and V inhibitors.

  20. A comparison of chemiluminescent acridinium dimethylphenyl ester labels with different conjugation sites.

    Science.gov (United States)

    Natrajan, Anand; Wen, David

    2015-03-01

    Chemiluminescent acridinium dimethylphenyl esters are highly sensitive labels that are used in automated assays for clinical diagnosis. Light emission from these labels and their conjugates is triggered by treatment with alkaline peroxide. Conjugation of acridinium ester labels is normally done at the phenol. During the chemiluminescent reaction of these acridinium esters, the phenolic ester is cleaved and the light emitting acridone moiety is liberated from its conjugate partner. In the current study, we report the synthesis of three new acridinium esters with conjugation sites at the acridinium nitrogen and compare their properties with that of a conventional acridinium ester with a conjugation site at the phenol. Our study is the first that provides a direct comparison of the emissive properties of acridinium dimethylphenyl esters (free labels and protein conjugates) with different conjugation sites, one where the light emitting acridone remains attached to its conjugate partner versus conventional labeling which results in cleavage of the acridone from the conjugate. Our results indicate that the conjugation at the acridinium nitrogen, which also alters how the acridinium ring and phenol are oriented with respect to the protein surface, has a minimal impact on emission kinetics and emission spectra. However, this mode of conjugation to three different proteins led to a significant increase in light yield which should be useful for improving the assay sensitivity. PMID:25581208

  1. Astonishing diversity of natural surfactants: 6. Biologically active marine and terrestrial alkaloid glycosides.

    Science.gov (United States)

    Dembitsky, Valery M

    2005-11-01

    This review article presents 209 alkaloid glycosides isolated and identified from plants, microorganisms, and marine invertebrates that demonstrate different biological activities. They are of great interest, especially for the medicinal and/or pharmaceutical industries. These biologically active glycosides have good potential for future chemical preparation of compounds useful as antioxidants, anticancer, antimicrobial, and antibacterial agents. These glycosidic compounds have been subdivided into several groups, including: acridone; aporphine; benzoxazinoid; ergot; indole; enediyne alkaloidal antibiotics; glycosidic lupine alkaloids; piperidine, pyridine, pyrrolidine, and pyrrolizidine alkaloid glycosides; glycosidic quinoline and isoquinoline alkaloids; steroidal glycoalkaloids; and miscellaneous alkaloid glycosides. PMID:16459921

  2. ALCALOIDES ACRIDÔNICOS INIBEM CATEPSINA L E V

    OpenAIRE

    Emerson F. Marques; Vieira, Paulo C.; Richele P. Severino

    2016-01-01

    Cathepsins represent a class of enzymes that has the primary function of randomly degrading proteins in the lysosomes, although are also involved in different pathologies. The aim of this paper was to evaluate the capacity of acridone alkaloids isolated from Swinglea glutinosa (Rutaceae) to inhibit cathepsin L in vitro . The IC50 values found were in the 0.8-57 µM range and the most promising compounds were alkaloids 1 and 2, with IC50 of 0.9 and 0.8 µM, respectively. Enzyme kinetics revealed...

  3. Chemiluminescence accompanied by the reaction of acridinium ester and manganese (II).

    Science.gov (United States)

    Ren, Lingling; Cui, Hua

    2014-11-01

    An acridinium ester (AE) alkaline solution can react with Mn(II) to generate a strong chemiluminescence (CL) centered at 435 nm. The effects of reaction conditions such as pH and Mn(II) concentration on CL intensity were examined. In order to explore the CL mechanism, the effect of oxygen on the CL reaction was examined and an X-ray photoelectron spectroscopy study of the reaction precipitate was carried out. The results indicated that oxygen participated in the CL reaction and Mn(IV) was the primary product in the system. A possible mechanism was proposed that involved two pathways: (1) dissolved oxygen was reduced to reactive oxygen radicals by Mn(II), these reactive intermediates then reacted with AE to produce excited state acridone; (2) Mn(II) could reduce AE to partly reduced AE, which then reacted with oxygen to form excited state acridone. The reactions of other metal ions with AE were also tested, and only Mn(II) was shown to trigger strong CL emission of AE, which indicated that the system had good selectivity for Mn(II). PMID:24677387

  4. Evaluation of new iodinated acridine derivatives for targeted radionuclide therapy of melanoma using 125I, an Auger electron emitter.

    Science.gov (United States)

    Gardette, Maryline; Papon, Janine; Bonnet, Mathilde; Desbois, Nicolas; Labarre, Pierre; Wu, Ting-Dee; Miot-Noirault, Elisabeth; Madelmont, Jean-Claude; Guerquin-Kern, Jean-Luc; Chezal, Jean-Michel; Moins, Nicole

    2011-12-01

    The increasing incidence of melanoma and the lack of effective therapy on the disseminated form have led to an urgent need for new specific therapies. Several iodobenzamides or analogs are known to possess specific affinity for melanoma tissue. New heteroaromatic derivatives have been designed with a cytotoxic moiety and termed DNA intercalating agents. These compounds could be applied in targeted radionuclide therapy using (125)I, which emits Auger electrons and gives high-energy, localized irradiation. Two iodinated acridine derivatives have been reported to present an in vivo kinetic profile conducive to application in targeted radionuclide therapy. The aim of the present study was to perform a preclinical evaluation of these compounds. The DNA intercalating property was confirmed for both compounds. After radiolabeling with (125)I, the two compounds induced in vitro a significant radiotoxicity to B16F0 melanoma cells. Nevertheless, the acridine compound appeared more radiotoxic than the acridone compound. While cellular uptake was similar for both compounds, SIMS analysis and in vitro protocol showed a stronger affinity for melanin with acridone derivative, which was able to induce a predominant scavenging process in the melanosome and restrict access to the nucleus. In conclusion, the acridine derivative with a higher nuclear localization appeared a better candidate for application in targeted radionuclide therapy using (125)I. PMID:20567996

  5. Rapid analysis of biogenic amines from rice wine with isotope-coded derivatization followed by high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Cai, Yiping; Sun, Zhiwei; Chen, Guang; Liu, Xiaomei; You, Jinmao; Zhang, Caiqing

    2016-02-01

    A pair of isotope-coded derivatization reagents, d0-10-methyl-acridone-2-sulfonyl chloride (d0-MASC, light form) and d3-10-methyl-acridone-2-sulfonyl chloride (d3-MASC, heavy form), were used for labeling biogenic amines (BAs). On basis of the isotope-coded derivatization, a global isotope internal standard quantitative method for determining seven BAs by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed. The d0-MASC and d3-MASC can easily label BAs under mild conditions within 15 min at 50 °C. The obtained light and heavy labeled BAs were monitored by the transitions of [M+H](+) → 208 and [M+H](+) → 211, respectively. Relative quantification of BAs was achieved by calculation of the peak area ratios of d0-MASC/d3-MASC labeled derivatives. Excellent linear responses for relative quantification were observed in the range of 1/10-10/1. The developed method has been successfully applied to the quantification of BAs in Chinese rice wine with recoveries ranging from 94.9% to 104.5%. PMID:26304364

  6. A new screening method for flunitrazepam in vodka and tequila by fluorescence spectroscopy.

    Science.gov (United States)

    Leesakul, Nararak; Pongampai, Sirintip; Kanatharana, Proespichaya; Sudkeaw, Pravit; Tantirungrotechai, Yuthana; Buranachai, Chittanon

    2013-01-01

    A new screening method for flunitrazepam in colourless alcoholic beverages based on a spectroscopic technique is proposed. Absorption and steady-state fluorescence of flunitrazepam and its protonated form with various acids were investigated. The redshift of the wavelength of maximum absorption was distinctively observed in protonated flunitrazepam. An emissive fluorescence at 472 nm was detected in colourless spirits (vodka and tequila) at room temperature. 2-M perchloric acid was the most appropriated proton source. By using electron ionization mass spectrometry and time-dependent density functional theory calculations, the possible structure of protonated flunitrazepam was identified to be 2-nitro-N-methylacridone, an acridone derivative as opposed to 2-methylamino-5-nitro-2'-fluorobenzophenone, a benzophenone derivative.

  7. Algicide constituents from Swinglea glutinosa.

    Science.gov (United States)

    Purcaro, Raffaella; Schrader, Kevin K; Burandt, Charles; DellaGreca, Marina; Meepagala, Kumudini M

    2009-11-25

    Oscillatoria perornata, a cyanobacterium (blue-green alga), common in catfish production ponds in the southeastern United States, produces the monoterpene 2-methylisoborneol (MIB), which is absorbed into catfish flesh and imparts a "musty" taste, rendering them unpalatable and unmarketable. Algicides that are currently in the commercial market to control O. perornata have broad-spectrum toxicity toward other beneficial phytoplankton, such as the green alga Selenastrum capricornutum, as well as low biodegradability. As part of our continuing efforts to search for natural-product-based algicides, the ethyl acetate extract of the roots of Swinglea glutinosa was investigated. This report describes isolation and structure elucidation of one novel coumarin, two known coumarins, and nine acridone alkaloids from S. glutinosa root extracts and the evaluation of these compounds for algicidal activity against O. perornata. PMID:19877680

  8. Synthesis, cytotoxic study and docking based multidrug resistance modulator potential analysis of 2-(9-oxoacridin-10(9H)-yl)-N-phenyl acetamides.

    Science.gov (United States)

    Kumar, Rajesh; Kaur, Maninder; Bahia, Malkeet Singh; Silakari, Om

    2014-06-10

    The present study describes the synthesis of fifteen 2-(9-oxoacridin-10(9H)-yl)-N-phenyl acetamide derivatives (13a-o) through condensation of 2-chloro-N-phenyl acetamides (12a-o) with acridone molecule (10). All the synthesized compounds were screened for their anti-cancer activity against three diverse cell lines including breast (MCF-7), cervical (HeLa) and lung adenocarcinoma (A-549) employing standard MTT assay. Among synthesized molecules, 13k and 13l showed good cytotoxicity activity against considered three cancer cell lines. Additionally, in silico studies of multidrug resistance modulator (MDR) effects of these compounds was performed by docking simulation in the ATP binding site of P-gp. The results of docking simulation displayed important interactions of these molecules in the active site of this protein and predicted their MDR modulator behavior. PMID:24769346

  9. Investigation of cytotoxic activity on human cancer cell lines of arborinine and furanoacridones isolated from Ruta graveolens.

    Science.gov (United States)

    Réthy, Borbála; Zupkó, István; Minorics, Renáta; Hohmann, Judit; Ocsovszki, Imre; Falkay, George

    2007-01-01

    The cytotoxic effects of a series of furanoacridones isolated from Ruta graveolens L. (Rutaceae) and of two further acridone alkaloids (arborinine and evoxanthine) were investigated by means of the MTT assay, using the human cell lines HeLa, MCF7 and A431. Arborinine proved best in inhibiting the proliferation of all three cell lines. The cytotoxic potency of the furacridone alkaloids was a function of their lipid solubility, which was determined by means of PAMPA. The capacity of the most effective furanoacridones to induce apoptosis was demonstrated by flow cytometric cell cycle analysis and by staining with ethidium bromide and acridine orange. This finding was reinforced by determining the apoptosis-regulating factors Bcl-2 and Bax, which were revealed by means of RT-PCR to change dose-dependently. The data presented here indicate that naturally occurring furanoacridones can be regarded as excellent starting structures for the potential development of new anticancer agents.

  10. Inhibition of RNA Helicases of ssRNA+ Virus Belonging to Flaviviridae, Coronaviridae and Picornaviridae Families

    Directory of Open Access Journals (Sweden)

    Irene Briguglio

    2011-01-01

    Full Text Available Many viral pathogens encode the motor proteins named RNA helicases which display various functions in genome replication. General strategies to design specific and selective drugs targeting helicase for the treatment of viral infections could act via one or more of the following mechanisms: inhibition of the NTPase activity, by interferences with ATP binding and therefore by limiting the energy required for the unwinding and translocation, or by allosteric mechanism and therefore by stabilizing the conformation of the enzyme in low helicase activity state; inhibition of nucleic acids binding to the helicase; inhibition of coupling of ATP hydrolysis to unwinding; inhibition of unwinding by sterically blocking helicase translocation. Recently, by in vitro screening studies, it has been reported that several benzotriazole, imidazole, imidazodiazepine, phenothiazine, quinoline, anthracycline, triphenylmethane, tropolone, pyrrole, acridone, small peptide, and Bananin derivatives are endowed with helicase inhibition of pathogen viruses belonging to Flaviviridae, Coronaviridae, and Picornaviridae families.

  11. Oxidative burst inhibition, cytotoxicity and antibacterial acriquinoline alkaloids from Citrus reticulate (Blanco).

    Science.gov (United States)

    Fomani, Marie; Ngeufa Happi, Emmanuel; Nouga Bisoue, Achille; Ndom, Jean Claude; Kamdem Waffo, Alain François; Sewald, Norbert; Wansi, Jean Duplex

    2016-01-15

    Two novel acridone-quinoline alkaloids, acriquinoline A (1) and acriquinoline B (2), together with twenty-two known compounds were isolated from the methanol extract of the root of Citrus reticulata Blanco. The structures of all compounds were determined by comprehensive analyses of their 1D and 2D NMR and mass spectral (EI and ESI) data. The possible biosynthesis for the formation of above compounds is proposed, based on close examination of their structures. Compounds 1, 2, 6, 10 and 14-17 exhibited strong suppressive effect on phagocytosis response upon activation with serum opsonized zymosan in the range of IC50 0.2-10.5μM, which was tested in vitro for oxidative burst studies of whole blood. However, compounds displayed low cytotoxic activity against the human Caucasian prostate adenocarcinoma cell line PC-3, with IC50 between 30.8 and 60.5μM compared to the standard doxorubicin with IC50 0.9μM. These compounds, tested against bacteria, fungi and plant pathogen oomycetes by the paper disk agar diffusion assay, resulting in missing to low activities corresponding with MICs>1mg/mL. PMID:26711890

  12. De Novo transcriptome assembly (NGS) of Curcuma longa L. rhizome reveals novel transcripts related to anticancer and antimalarial terpenoids.

    Science.gov (United States)

    Annadurai, Ramasamy S; Neethiraj, Ramprasad; Jayakumar, Vasanthan; Damodaran, Anand C; Rao, Sudha Narayana; Katta, Mohan A V S K; Gopinathan, Sreeja; Sarma, Santosh Prasad; Senthilkumar, Vanitha; Niranjan, Vidya; Gopinath, Ashok; Mugasimangalam, Raja C

    2013-01-01

    Herbal remedies are increasingly being recognised in recent years as alternative medicine for a number of diseases including cancer. Curcuma longa L., commonly known as turmeric is used as a culinary spice in India and in many Asian countries has been attributed to lower incidences of gastrointestinal cancers. Curcumin, a secondary metabolite isolated from the rhizomes of this plant has been shown to have significant anticancer properties, in addition to antimalarial and antioxidant effects. We sequenced the transcriptome of the rhizome of the 3 varieties of Curcuma longa L. using Illumina reversible dye terminator sequencing followed by de novo transcriptome assembly. Multiple databases were used to obtain a comprehensive annotation and the transcripts were functionally classified using GO, KOG and PlantCyc. Special emphasis was given for annotating the secondary metabolite pathways and terpenoid biosynthesis pathways. We report for the first time, the presence of transcripts related to biosynthetic pathways of several anti-cancer compounds like taxol, curcumin, and vinblastine in addition to anti-malarial compounds like artemisinin and acridone alkaloids, emphasizing turmeric's importance as a highly potent phytochemical. Our data not only provides molecular signatures for several terpenoids but also a comprehensive molecular resource for facilitating deeper insights into the transcriptome of C. longa.

  13. Design and study of telomerase inhibitors based on G-quadruplex ligands

    Directory of Open Access Journals (Sweden)

    Negrutska V. V.

    2013-05-01

    Full Text Available In this review we have summarized the results of our recent research on telomerase inhibitors and G-quadruplex DNA ligands. A series of potential enzyme inhibitors were synthesized and studied. These compounds were based on tricyclic heteroaromatic systems (thiazolobenzimidazoles phenazines, acridones, amino-substituted cyanines and natural and synthetic porphyrins and their metalocomplexes. A number of compounds, including cyanines and especially porphyrin derivatives and conjugates, were found to efficiently inhibit telomerase at low micromolar concentrations in the in vitro TRAP assay. Porphyrins demonstrated antiproliferative activity in tumor cell cultures at micro- and nanomolar concentrations. Spectral-fluorescent and electrophoretic experiments were performed to investigate the interaction of ligands with duplex and quadruplex DNA, and in many cases binding mode was established. Convenient G-octet model of G-quadruplex was developed to study the ligand-target binding using quantum-chemical methods. QM/MM hybrid approach ONIUM2 was employed to model the interaction of small molecules with Tel22 quadruplex DNA.

  14. Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

    Directory of Open Access Journals (Sweden)

    Louis P. Sandjo

    2015-09-01

    Full Text Available This review focuses on pyridoacridine-related metabolites as one biologically interesting group of alkaloids identified from marine sources. They are produced by marine sponges, ascidians and tunicates, and they are structurally comprised of four to eight fused rings including heterocycles. Acridine, acridone, dihydroacridine, and quinolone cores are features regularly found in these alkaloid skeletons. The lack of hydrogen atoms next to quaternary carbon atoms for two or three rings makes the chemical shift assignment a difficult task. In this regard, one of the aims of this review is the compilation of previously reported, pyridoacridine 13C NMR data. Observations have been made on the delocalization of electrons and the presence of some functional groups that lead to changes in the chemical shift of some carbon resonances. The lack of mass spectra information for these alkaloids due to the compactness of their structures is further discussed. Moreover, the biosynthetic pathways of some of these metabolites have been shown since they could inspire biomimetic synthesis. The synthesis routes used to prepare members of these marine alkaloids (as well as their analogues, which are synthesized for biological purposes are also discussed. Pyridoacridines were found to have a large spectrum of bioactivity and this review highlights and compares the pharmacophores that are responsible for the observed bioactivity.

  15. Molecular evolution and sequence divergence of plant chalcone synthase and chalcone synthase-Like genes.

    Science.gov (United States)

    Han, Yingying; Zhao, Wenwen; Wang, Zhicui; Zhu, Jingying; Liu, Qisong

    2014-06-01

    Plant chalcone synthase (CHS) and CHS-Like (CHSL) proteins are polyketide synthases. In this study, we evaluated the molecular evolution of this gene family using representative types of CHSL genes, including stilbene synthase (STS), 2-pyrone synthase (2-PS), bibenzyl synthase (BBS), acridone synthase (ACS), biphenyl synthase (BIS), benzalacetone synthase, coumaroyl triacetic acid synthase (CTAS), and benzophenone synthase (BPS), along with their CHS homologs from the same species of both angiosperms and gymnosperms. A cDNA-based phylogeny indicated that CHSLs had diverse evolutionary patterns. STS, ACS, and 2-PS clustered with CHSs from the same species (late diverged pattern), while CTAS, BBS, BPS, and BIS were distant from their CHS homologs (early diverged pattern). The amino-acid phylogeny suggested that CHS and CHSL proteins formed clades according to enzyme function. The CHSs and CHSLs from Polygonaceae and Arachis had unique evolutionary histories. Synonymous mutation rates were lower in late diverged CHSLs than in early diverged ones, indicating that gene duplications occurred more recently in late diverged CHSLs than in early diverged ones. Relative rate tests proved that late diverged CHSLs had unequal rates to CHSs from the same species when using fatty acid synthase, which evolved from the common ancestor with the CHS superfamily, as the outgroup, while the early diverged lineages had equal rates. This indicated that late diverged CHSLs experienced more frequent mutation than early diverged CHSLs after gene duplication, allowing obtaining new functions in relatively short period of time.

  16. Phytochemistry and pharmacognosy of the genus Acronychia.

    Science.gov (United States)

    Epifano, Francesco; Fiorito, Serena; Genovese, Salvatore

    2013-11-01

    The genus Acronychia (Rutaceae) comprise 44 species, most of which are represented by shrubs and small trees, distributed in a wide geographical area of South-Eastern Asia comprising China, India, Malaysia, Indonesia, Australia, and the islands of the western Pacific Ocean. Most of the species of the genus Acronychia have been used for centuries as natural remedies in the ethnomedical traditions of indigenous populations as anti-microbial, anti-fungal, anti-spasmodic, stomachic, anti-pyretic, and anti-haemorragic agent. Moreover fruits and aerial parts are used as food in salads and condiments, while the essential oil obtained from flowers and leaves has been employed in cosmetics production. Phytochemicals isolated from Acronychia spp. include acetophenones, quinoline and acridone alkaloids, flavonoids, cinnamic acids, lignans, coumarins, steroids, and triterpenes. The reported biological activities of the above mentioned natural compounds refer to anti-plasmodial, anti-cancer, anti-oxidant, anti-inflammatory, anti-fungal, and neuroprotective effects. The aim of this review is to examine in detail from a phytochemical and pharmacologically point of view what is reported in the current literature about the properties of phytopreparations or individual active principles obtained from plants belonging to the Acronychia genus. PMID:23920228

  17. De Novo transcriptome assembly (NGS of Curcuma longa L. rhizome reveals novel transcripts related to anticancer and antimalarial terpenoids.

    Directory of Open Access Journals (Sweden)

    Ramasamy S Annadurai

    Full Text Available Herbal remedies are increasingly being recognised in recent years as alternative medicine for a number of diseases including cancer. Curcuma longa L., commonly known as turmeric is used as a culinary spice in India and in many Asian countries has been attributed to lower incidences of gastrointestinal cancers. Curcumin, a secondary metabolite isolated from the rhizomes of this plant has been shown to have significant anticancer properties, in addition to antimalarial and antioxidant effects. We sequenced the transcriptome of the rhizome of the 3 varieties of Curcuma longa L. using Illumina reversible dye terminator sequencing followed by de novo transcriptome assembly. Multiple databases were used to obtain a comprehensive annotation and the transcripts were functionally classified using GO, KOG and PlantCyc. Special emphasis was given for annotating the secondary metabolite pathways and terpenoid biosynthesis pathways. We report for the first time, the presence of transcripts related to biosynthetic pathways of several anti-cancer compounds like taxol, curcumin, and vinblastine in addition to anti-malarial compounds like artemisinin and acridone alkaloids, emphasizing turmeric's importance as a highly potent phytochemical. Our data not only provides molecular signatures for several terpenoids but also a comprehensive molecular resource for facilitating deeper insights into the transcriptome of C. longa.

  18. Cloning, expression and functional identification of a type Ⅲ polyketide synthase gene from Huperzia serrata%千层塔中Ⅲ型聚酮合酶基因的克隆、表达与功能鉴定

    Institute of Scientific and Technical Information of China (English)

    叶金翠; 张萍; 孙洁胤; 郭潮潭; 陈国神; 阿部郁朗; 野口博司

    2011-01-01

    Ⅲ型聚酮合酶是以合成聚酮类化合物为主的一类重要生物合成酶.本文利用逆转录聚合酶链反应从中草药千层塔新鲜嫩叶中扩增聚酮合酶基因,得到一个Ⅲ型聚酮合酶全长cDNA.该基因全长1 212 bp,编码404个氨基酸.与已知的其他植物来源的聚酮合酶氨基酸序列有约50%~66%的同源性.cDNA经双酶切后克隆至pQE81L,并导入大肠杆菌(E.coli) M15中表达,产生大量带寡聚组氨酸标记的重组酶,重组酶分子质量大小约为46.4 kDa.酶活性鉴定研究表明,该重组酶可催化芳香族底物、脂肪族底物生成系列非天然聚酮产物,尤其是其可催化N-甲基邻氨基苯甲酰CoA和丙二酰CoA生成1,3-二羟基-N-甲基-吖啶酮,吖啶酮生物碱一直被认为只能由吖啶酮合酶合成.该工作为研究千层塔中Ⅲ型聚酮合酶在天然药物石杉碱甲生物合成中的作用奠定基础.%A Cdna encoding novel type III polyketide synthase (PKS) was cloned and sequenced from young leaves of Chinese club moss Huperzia serrata (Thunb.) Trev. By RT-PCR using degenerated primers based on the conserved sequences of known CHSs, and named as H. Serrata PKS2. The terminal sequences of Cdna were obtained by the 3'- and 5'-RACE method. The full-length Cdna ofH, serrata PKS2 contained a 1 212 bp open reading frame encoding a 46.4 kDa protein with 404 amino acids. The deduced amino acid sequence of H. Serrata PKS2 showed 50%-66% identities to those of other chalcone synthase super family enzymes of plant origin. The recombinant H. Serrata PKS2 was functionally expressed in Escherichia coli with an additional hexahistidine tag at the N-terminus and showed unusually versatile catalytic potency to produce various aromatic tetraketides, including chalcones, benzophenones, phloroglucinols, and acridones. In particular, the enzyme accepted bulky starter substrates N-methylanthraniloyl-CoA, and carried out three condensations with malonyl-CoA to produce 1

  19. Evaluation of new iodinated acridine derivatives for targeted radionuclide therapy of melanoma using 125I, an Auger electron emitter

    International Nuclear Information System (INIS)

    The full text of the publication follows. The increasing incidence of melanoma and the lack of effective therapy on the disseminated form have led to an urgent need for new specific therapies. Several iodo-benzamides or analogs are known to possess specific affinity for melanoma tissue. New hetero-aromatic derivatives have been designed with a cytotoxic moiety and termed DNA intercalating agents. These compounds could be applied in targeted radionuclide therapy using 125I, Auger electrons emitter which gives high-energetic localized irradiation. Two iodinated acridine derivatives have been reported to present an in vivo kinetic profile conducive to application in targeted radionuclide therapy. The aim of the present study was to perform a preclinical evaluation of these compounds. The DNA intercalating property was confirmed for both compounds. After radiolabeling with 125I, the two compounds induced in vitro a significant radiotoxicity on B16F0 melanoma cells. The acridine compound, ICF01040, appeared more radio toxic than the acridone compound, ICF01035. While cellular uptake was similar for both compounds, SIMS analysis and in vitro protocol showed a stronger affinity for melanin with ICF01035, which was able to induce a predominant scavenging process in the melanosome and restrict access to the nucleus. Nevertheless, an important radiotoxicity was measured for the two compounds while the nuclear accumulation was low. Indeed, even if nuclear localization remains the main target sensitive to Auger electrons, the cell membrane remains sensitive to 125I decays. So, these compounds may induce secondary toxic effects of irradiation, such as membrane lipid damage. Conducted to current experiments are evaluate such hypothesis. Taken together, these results suggest that ICF01040 is a better candidate for application in targeted radionuclide therapy using 125I. The next step will be in vivo evaluation, where high tumoral vectorization gives promising perspectives

  20. [Determination of L-dopa and dopamine in rat brain microdialysate by ultra high performance liquid chromatography-tandem mass spectrometry using stable isotope-coded derivatization coupled with dispersive liquid-liquid microextraction].

    Science.gov (United States)

    Qi, Weimei; Zhao, Xian-en; Qi, Yong; Sun, Zhiwei; Chen, Guang; You, Jinmao; Suo, Yourui

    2015-09-01

    The sensitive detection method of levodopa (L-DOPA) and dopamine (DA) in rat brain microdialysate of Parkinson's disease (PD) is an essential tool for the clinical study and attenuated synergistic drug screening for L-DOPA from traditional Chinese medicines. Using d0/d3-10-methyl-acridone-2-sulfonyl chloride (d0/d3-MASC) as stable isotope derivatization reagent, a novel ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for L-DOPA and DA by stable isotope- coded derivatization coupled with ultrasonic-assisted dispersive liquid-liquid microextraction (UA-DLLME). d3-MASC (light) and d3-MASC (heavy) were used as derivatization reagents for microdialysate samples and standards, respectively. Mixtures of the two solutions were prepared by UA-DLLME for UHPLC-MS/MS analysis with multiple reaction monitoring (MRM) mode. With d3-MASC heavy derivatives as internal standards for corresponding light derivatives from samples, the stable isotope internal standard quantification for L-DOPA and DA was carried out. The stable derivatives were obtained in aqueous acetonitrile (pH 10.8 sodium carbonate-sodium bicarbonate buffer) at 37 °C for 3.0 min, and then were separated within 2.0 min using gradient elution. Linear range was 0.20-1500.0 nmol/L (R > 0.994). LODs were 0.005 and 0.009 nmol/L for DA and L-DOPA (S/N = 3), respectively. This method was validated, and it showed obvious advantages in comparing with the reported methods in terms of sensitivity, analysis speed and anti-matrix interference. This method has been successfully applied to the study of effect of Shouwu Fang on L-DOPA and DA concentration fluctuations in PD rat brain microdialysate.

  1. Removal of carbamazepine in aqueous solutions through solar photolysis of free available chlorine.

    Science.gov (United States)

    Yang, Bin; Kookana, Rai S; Williams, Mike; Du, Jun; Doan, Hai; Kumar, Anupama

    2016-09-01

    Removal of a persistent antiepileptic drug carbamazepine (CBZ) in aqueous solutions was investigated by using solar photolysis combined with free available chlorine (FAC). The combination of chlorination with simulated or natural sunlight markedly enhanced removal of CBZ in 10 mM phosphate buffer solution (pH 7.0) and river water (pH 7.0) compared with sunlight or FAC alone. Further analysis indicated that the observed enhancements in CBZ removal can be attributed to the in situ hydroxyl radical (HO) and ozone (O3) production during FAC photolysis. During 70 min simulated sunlight photolysis combined with FAC treatment, HO reaction contributed to 35.8% removal of CBZ and O3 reaction contributed to 40.6% removal, while only 5.3% of CBZ was removed by HOCl reaction. The oxidation products of CBZ, epoxide CBZ, 10,11-dihydro-10,11-dihydroxy CBZ, 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM), 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD) and 4-aldehyde-9-acridone, were mainly formed from the HO and O3 attack at the double bond on the central heterocyclic ring of CBZ. Formation of these oxidation products did not cause any increase or decrease in toxicity to microbial species tested through Microbial Assay for Toxicity Risk Assessment (MARA). The initial FAC concentration and pH had a major influence on the removal process of CBZ during FAC photolysis, while temperature had a minor effect only. The combination of chlorination with natural sunlight could provide an effective approach for removal of CBZ and other contaminants during water treatment. PMID:27232985

  2. Application of chitin and chitosan as elicitors of coumarins and fluoroquinolone alkaloids in Ruta graveolens L. (common rue).

    Science.gov (United States)

    Orlita, Aleksandra; Sidwa-Gorycka, Matylda; Paszkiewicz, Monika; Malinski, Edmund; Kumirska, Jolanta; Siedlecka, Ewa M; Łojkowska, Ewa; Stepnowski, Piotr

    2008-10-01

    Common rue (Ruta graveolens L.) accumulates various types of secondary metabolites, such as coumarins furanocoumarins, acridone and quinolone alkaloids and flavonoids. Elicitation is a tool extensively used for enhancing secondary-metabolite yields. Chitin and chitosan are examples of elicitors inducing phytoalexin accumulation in plant tissue. The present paper describes the application of chitin and chitosan as potential elicitors of secondary-metabolite accumulation in R. graveolens shoots cultivated in vitro. The simple coumarins, linear furanocoumarins, dihydrofuranocoumarins and fluoroquinolone alkaloids biosynthesized in the presence of chitin and chitosan were isolated, separated and identified. There was a significant increase in the growth rate of R. graveolens shoots in the presence of either chitin or chitosan. Moreover, the results of the elicitation of coumarins and alkaloids accumulated by R. graveolens shoots in the presence of chitin and chitosan show that both compounds induced a significant increase in the concentrations of nearly all the metabolites. Adding 0.01% chitin caused the increase in the quantity (microg/g dry weight) of coumarins (pinnarin up to 116.7, rutacultin up to 287.0, bergapten up to 904.3, isopimpinelin up to 490.0, psoralen up to 522.2, xanhotoxin up to 1531.5 and rutamarin up to 133.7). The higher concentration of chitosan (0.1%) induced production of simple coumarins (pinnarin up to 116.7 and rutacultin up to 287.0), furanocoumarins (bergapten up to 904.3, isopimpinelin up to 490.0, psoralen up to 522.2, xanhotoxin up to 1531.5) and dihydrofuranocoumarins (chalepin up to 18 and rutamarin up to 133.7). Such a dramatic increase in the production of nearly all metabolites suggests that these compounds may be participating in the natural resistance mechanisms of R. graveolens. The application of chitin- and chitosan-containing media may be considered a promising prospect in the biotechnological production of xanthotoxin

  3. Unusually divergent 4-coumarate:CoA-ligases from Ruta graveolens L.

    Science.gov (United States)

    Endler, Alexander; Martens, Stefan; Wellmann, Frank; Matern, Ulrich

    2008-07-01

    Most angiosperms encode a small family of 4-coumarate:CoA-ligases (4CLs) activating hydroxycinnamic acids for lignin and flavonoid pathways. The common rue, Ruta graveolens L., additionally produces coumarins by cyclization of the 4-coumaroyl moiety, possibly involving the CoA-ester, as well as acridone and furoquinoline alkaloids relying on (N-methyl)anthraniloyl-CoA as the starter substrate for polyketide synthase condensation. The accumulation of alkaloids and coumarins, but not flavonoids, was enhanced in Ruta graveolens suspension cultures upon the addition of fungal elicitor. Total RNA of elicitor-treated Ruta cells was used as template for RT-PCR amplification with degenerate oligonucleotide primers inferred from conserved motifs in AMP-binding proteins, and two full-size cDNAs were generated through RACE and identified as 4-coumarate:CoA-ligases, Rg4CL1 and Rg4CL2, by functional expression in yeast cells. The recombinant enzymes differed considerably in their preferential affinities to cinnamate (Rg4CL1) or ferulate (RgCL2) besides 4-coumarate, but did not activate hydroxybenzoic or (N-methyl)anthranilic acid. Most notably, the Rg4CL1 polypeptide included an N-terminal extension suggesting a chloroplast transit peptide. The genes were cloned and revealed four exons, separated by 1056, 94 and 54 bp introns for RgCL1, while Rg4CL2 was composed of five exons interupted by four introns from 113 to 350 bp, and the divergent heritage of these genes was substantiated by phylogenetic analysis. Both genes were expressed in shoot, leaf and flower tissues of adult Ruta plants with preference in shoot and flower, whereas negligible expression occurred in the root. However, Rg4CL1 was expressed much stronger in the flower, while Rg4CL2 was expressed mostly in the shoot. Furthermore, considerable transient induction of only Rg4CL1 was observed upon elicitation of Ruta cells, which seems to support a role of Rg4CL1 in coumarin biosynthesis.