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1

Bioactive naphthoquinones from Cordyceps unilateralis  

Microsoft Academic Search

Six bioactive naphthoquinone derivatives, erythrostominone, deoxyerythrostominone, 4-O-methyl erythrostominone, epierythrostominol, deoxyerythrostominol and 3,5,8-trihydroxy-6-methoxy-2-(5-oxohexa-1,3-dienyl)-1,4-naphthoquinone, were isolated from the insect pathogenic fungus Cordyceps unilateralis BCC1869. While the latter is synthetically known, both it and 4-O-methyl erythrostominone are products of fungus strain C. unilateralis BCC1869.

Prasat Kittakoop; Juntira Punya; Palangpon Kongsaeree; Yuwapin Lertwerawat; Amnuay Jintasirikul; Morakot Tanticharoen; Yodhathai Thebtaranonth

1999-01-01

2

A new naphthoquinone from Ceiba pentandra.  

PubMed

A new naphthoquinone, 2,7-dihydroxy-8-formyl-5-isopropyl-3-methyl-1,4-naphthoquinone (1) together with a known naphthoquinone, 8-formyl-7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthoquinone (2), has been isolated from the heartwood of Ceiba pentandra. The structures of 1 and 2 have been elucidated by extensive 1D and 2D NMR experiments. PMID:12931857

Kishore, P Hari; Reddy, M Vijaya Bhaskar; Gunasekar, D; Caux, Cristelle; Bodo, Bernard

2003-09-01

3

Leishmanicidal activity of two naphthoquinones against L. donovani  

PubMed Central

Here we studied ability of two naphthoquinones to inhibit Leishmania growth (2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (TR 001) and 2,3-dibromo-1,4-naphthoquinone (TR 002). TR 001 was more efficient than TR 002 in inducing killing of promastigotes and intracellular amastigotes. These values compare well to those obtained with the standard first-line antileishmanial agent sodium stibogluconate (SSG). TR 001 also induced significantly more nitric oxide (NO) production than TR 002 or SSG. Taken together, these data show that TR 001 and TR 002 could be promising new drugs for treatment of visceral leishmaniasis. PMID:23037165

Lezama-Davila, Claudio Manuel; Isaac-Marquez, Angelica Patricia; Kapadia, Govind; Owens, Katherine; Oghumu, Steve; Beverley, Stephen; Satoskar, Abhay Rajaninath

2013-01-01

4

Antitumor-promoting naphthoquinones from Catalpa ovata.  

PubMed

Bioassay-directed fractionation of an extract of the stem-bark of Catalpa ovata led to the isolation of three new naphthoquinones: 8-methoxydehydroiso-alpha-lapachone (1), 9-methoxy-4-oxo-alpha-lapachone (2), and (4S,4aR,10R,10aR)-4, 10-dihydroxy-2,2-dimethyl-2,3,4,4alpha,10, 10alpha-hexahydrobenzo[g]chromen-5-one (3), which is a 1,4-reductive form of 6. The known compounds 3-hydroxydehydroiso-alpha-lapachone (4), 4,9-dihydroxy-alpha-lapachone (5), 4-hydroxy-alpha-lapachone (6), and 9-methoxy-alpha-lapachone (7), and catalpalactone (8) were also isolated. Their structures were elucidated by spectral methods. These compounds all exhibited significant inhibitory activity against 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation in Raji cells. PMID:9599262

Fujiwara, A; Mori, T; Iida, A; Ueda, S; Hano, Y; Nomura, T; Tokuda, H; Nishino, H

1998-05-01

5

Luciferase inhibition by a novel naphthoquinone.  

PubMed

The novel naphthoquinone 12,13-dihydro-N-methyl-6,11,13-trioxo-5H-benzo[4,5]cyclohepta[1,2-b]naphthalen-5,12-imine (hereafter called TU100) was created as a potential chemotherapeutic agent. Previous work showed it is an irreversible inhibitor of type I and II topoisomerases that alkylates specific enzyme thiols. While analyzing the effect of TU100 on cancer cells, we discovered it is a potent inhibitor of luciferase derived from both Photinus pyralis (fireflies) and Renilla reniformis (sea pansy). Pre-incubation experiments showed that TU100 does not irreversibly inactivate luciferase, indicating its mechanism is different from that observed with topoisomerases. Firefly luciferase generates light using ATP and luciferin as substrates (bioluminescence). An examination of TU100 inhibition at varying substrate concentrations revealed the drug is uncompetitive with respect to ATP and competitive with respect to luciferin. The TU100 binding constant (K(I)) is 2.5±0.7 ?M as determined by Dixon plot analysis. These data suggest TU100 specifically binds the luciferase-ATP complex and prevents its interaction with luciferin. Given the novel structure of TU100, unique mechanism of action, and ability to target luciferase from different species, these results identify TU100 as an important new reagent for investigating and regulating bioluminescent enzymes. PMID:22197716

Bedford, Rebecca; LePage, Daniel; Hoffmann, Rachel; Kennedy, Steven; Gutschenritter, Tyler; Bull, Lauren; Sujijantarat, Nanthiya; DiCesare, John C; Sheaff, Robert J

2012-02-01

6

The chemical biology of naphthoquinones and its environmental implications.  

PubMed

Quinones are a group of highly reactive organic chemical species that interact with biological systems to promote inflammatory, anti-inflammatory, and anticancer actions and to induce toxicities. This review describes the chemistry, biochemistry, and cellular effects of 1,2- and 1,4-naphthoquinones and their derivatives. The naphthoquinones are of particular interest because of their prevalence as natural products and as environmental chemicals, present in the atmosphere as products of fuel and tobacco combustion. 1,2- and 1,4-naphthoquinones are also toxic metabolites of naphthalene, the major polynuclear aromatic hydrocarbon present in ambient air. Quinones exert their actions through two reactions: as prooxidants, reducing oxygen to reactive oxygen species; and as electrophiles, forming covalent bonds with tissue nucleophiles. The targets for these reactions include regulatory proteins such as protein tyrosine phosphatases; Kelch-like ECH-associated protein 1, the regulatory protein for NF-E2-related factor 2; and the glycolysis enzyme glyceraldehyde-3-phosphate dehydrogenase. Through their actions on regulatory proteins, quinones affect various cell signaling pathways that promote and protect against inflammatory responses and cell damage. These actions vary with the specific quinone and its concentration. Effects of exposure to naphthoquinones as environmental chemicals can vary with the physical state, i.e., whether the quinone is particle bound or is in the vapor state. The exacerbation of pulmonary diseases by air pollutants can, in part, be attributed to quinone action. PMID:21942631

Kumagai, Yoshito; Shinkai, Yasuhiro; Miura, Takashi; Cho, Arthur K

2012-01-01

7

STABILITY OF HEMOGLOBIN AND ALBUMIN ADDUCTS OF NAPHTHALENE OXIDE, 1,2-NAPHTHOQUINONE, AND 1,4-NAPHTHOQUINONE  

EPA Science Inventory

Naphthalene is an important industrial chemical, which has recently been shown to cause tumors of the respiratory tract in rodents. It is thought that one or more reactive metabolites of naphthalene, namely, naphthalene-1,2-oxide (NPO), 1,2-naphthoquinone (1,2-NPQ), and 1,4-na...

8

An antileishmanial prenyloxy-naphthoquinone from roots of Plumbago zeylanica.  

PubMed

Leishmania donovani, an obligate intracellular parasite of genus Leishmania causes visceral leishmaniasis that affects millions of people worldwide, especially in the Indian subcontinent and East Africa. Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions due to efficacy and cost effectiveness but the growing incidence of their resistance has seriously hampered their use. This study discloses strong in vitro antileishmanial activity of 2-methyl-5?-(3'-methyl-but-2'-enyloxy)-[1,4]naphthoquinone (1), a prenyloxy-naphthoquinone isolated and characterised from roots of the plant Plumbago zeylanica (family-Plumbaginaceae). The observed EC50 for the compound 1 against promastigote and amastigote forms of L. donovani was significantly (p<0.001) lower than miltefosine, a reference drug. In context to limited treatment options and growing resistance for available drugs, compound 1 offers a greater prospect towards antileishmanial drug discovery and development. PMID:22708724

Mishra, Bhuwan B; Gour, Jalaj K; Kishore, Navneet; Singh, Rakesh K; Tripathi, Vyasji; Tiwari, Vinod K

2013-03-01

9

Conformational analysis of chloroalkyl derivatives of 1,4-naphthoquinone  

E-print Network

of the inductive effect of the naphthoquinone fragment propagating along the C­C bonds that negatively influenced July 1999 Abstract Studies of Kerr effect and 1 H and 13 C NMR spectra of 2-substituted 3-g CH3; Cl, Br, OH, OCH3, OCOCH3; R1 CH3; C2H5; R2 H; CH3. In parti- cular, the yield of the reaction

10

Cytotoxic naphthoquinones and plumbagic acid glucosides from Plumbago zeylanica.  

PubMed

Two plumbagic acid glucosides, 3'-O-beta-glucopyranosyl plumbagic acid and 3'-O-beta-glucopyranosyl plumbagic acid methylester along with five naphthoquinones (plumbagin, chitranone, maritinone, elliptinone and isoshinanolone), and five coumarins (seselin, 5-methoxyseselin, suberosin, xanthyletin and xanthoxyletin) were isolated from the roots of Plumbago zeylanica. All coumarins were not previously found in this plant. Cytotoxicity of these compounds to various tumor cells lines was evaluated, and plumbagin significantly suppressed growth of Raji, Calu-1, HeLa, and Wish tumor cell lines. PMID:12560036

Lin, Lie-Chwen; Yang, Ling-Ling; Chou, Cheng-Jen

2003-02-01

11

Cytotoxicity of new alkylamino- and phenylamino-containing polyfluorinated derivatives of 1,4-naphthoquinone.  

PubMed

Fluorinated derivatives of 1,4-naphthoquinone are highly potent inhibitors of Cdc25A and Cdc25 phosphatases and growth of tumor cells. Five new N-substituted polyfluorinated derivatives of 2-amino-1,4-naphthoquinone were synthesized and their mutagenic and antioxidant properties in Salmonella cells, as well as cytotoxicity in human myeloma (RPMI 8226), human mammary adenocarcinoma (MCF-7), mouse fibroblasts (LMTK) and primary mouse fibroblast cells (PMF) were studied. 2-tert-Butylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (1) inhibited the growth of normal control and tumor cells at the same concentration. Three compounds: 2-diethylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (2), 2-ethylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (3), 2-phenylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (4) exhibited a 50% decrease in the growth of cancer cells at low and comparable concentrations (2.4-8.6 microM) while being remarkably less cytotoxic toward normal LMTK and PMF cells. Quinones (1)-(4), but not 2-phenylamino-3-methyl-5,6,7,8-tetrafluoro-1,4-naphthoquinone (5), efficiently suppressed spontaneous mutagenesis in Salmonella cells, while all compounds 1-5 decreased the mutagenic effect of H2O2 on bacterial cells. Their possible perspectives as anticancer drugs are shortly discussed. PMID:20189692

Zakharova, Ol'ga D; Ovchinnikova, Ludmila P; Goryunov, Leonid I; Troshkova, Nadezhda M; Shteingarts, Vitalij D; Nevinsky, Georgy A

2010-06-01

12

Thermally Induced And Base Catalyzed Reactions Of Naphthoquinone Diazides  

NASA Astrophysics Data System (ADS)

Thermally induced and base catalyzed reactions of a phenol ester of 1,2-naphthoquinone-diazide-5-sulfonic acid (DAM) with p-cresol were investigated. In total seven reaction products were obtained for the thermally induced reaction. The three major products, TR--F4, TR-F6 and TR-F7, were isolated and their structures were determined by means of several advanced spectroscopic techniques like Fourier transform nuclear magnetic resonance (FTNMR) and field desorption mass spectroscopy (FD-MS). Besides a cresol ester of indenecarboxylic acid (TR-F6) and an azo compound which contains two DAM originated moieties and cresol (TR-F7), the formation of a novel compound was found; a phenol ester of 2-cresyl-l-naphthol-5-sulfonic acid. On the other hand, four reaction products were found in the base (a 2.38wt% tetramethylammonium hydroxide aq. solution) catalyzed reaction products of DAM with p-cresol, and two major products, BC-Fl and BC-F3, which appeared at the initial stage of the reaction were isolated. The structure determination of the two major products was carried out in the same manner as described above. It was discovered that BC-Fl was a cresol ester of 1-naphthol while BC-F3 was an azoxy compound. Brief discussions will be made on those reactions of naphthoquinone diazides with a matrix novolak resin with reference to the results obtained by the present study.

Koshiba, Mitsunobu; Murata, Makoto; Matsui, Mariko; Harita, Yoshiyuki

1988-01-01

13

Comparison of antimicrobial activities of naphthoquinones from Impatiens balsamina.  

PubMed

Lawsone (1), lawsone methyl ether (2), and methylene-3,3'-bilawsone (3) are the main naphthoquinones in the leaf extracts of Impatiens balsamina L. (Balsaminaceae). Antimicrobial activities of these three naphthoquinones against dermatophyte fungi, yeast, aerobic bacteria and facultative anaerobic and anaerobic bacteria were evaluated by determination of minimal inhibitory concentrations (MICs) and minimal bactericidal or fungicidal concentrations (MBCs or MFCs) using a modified agar dilution method. Compound 2 showed the highest antimicrobial activity. It showed antifungal activity against dermatophyte fungi and Candida albicans with the MICs and MFCs in the ranges of 3.9-23.4 and 7.8-23.4?µg?mL(-1), respectively, and also had some antibacterial activity against aerobic, facultative anaerobic and anaerobic bacteria with MICs in the range of 23.4-93.8, 31.2-62.5 and 125?µg?mL(-1), respectively. Compound 1 showed only moderate antimicrobial activity against dermatophytes (MICs and MFCs in the ranges of 62.5-250 and 125-250?µg?mL(-1), respectively), but had low potency against aerobic bacteria, and was not active against C. albicans and facultative anaerobic bacteria. In contrast, 3 showed significant antimicrobial activity only against Staphylococus epidermidis and Bacillus subtilis (MIC and MBC of 46.9 and 93.8?µg?mL(-1), respectively). PMID:21895457

Sakunphueak, Athip; Panichayupakaranant, Pharkphoom

2012-01-01

14

Apoptotic effect of Naphthoquinone derivatives on HCT116 colon cancer cells  

Microsoft Academic Search

Naphthoquinone is found in the core structure of many natural compounds, most notably the K vitamins. Numerous molecules with\\u000a the 1,4-naphthoquinone moiety are known to display distinct biological activities including anti-cancer, anti-inflammatory\\u000a and anti-bacterial activities. Vitamin K2 and doxorubicin, which are used to treat bleeding and lymphoma respectively, belong\\u000a to this class of chemicals. Although the exact mechanism of action

Young-Sam Im; Yongseog Chung; Dae Yeon Won; Soo Han Kwon; Hye-Ryun Kim; Dong Geun Lee; Seung-Ryul Kim; Kyung Do Park; Hak-Kyo Lee; Joong-Kook Choi

2010-01-01

15

Effects of a naphthoquinone analog on tumor growth and apoptosis induction  

Microsoft Academic Search

Vitamin K-related analogs induce growth inhibition in various cancer cell lines. A naphthoquinone analog, termed 2,3-dichloro-5,\\u000a 8-dihydroxy-1,4-naphthoquinone (DDN), induces apoptosis in human promyeloid leukemic HL-60 cells, and shows antitumor activity\\u000a in vivo. Following treatment with DDN, evidence of apoptosis, including DNA fragmentation and cleavage of poly ADP ribose\\u000a polymerase (PARP), was observed. DDN induced an upregulation of proapoptotic Bax protein,

Hae Jong Kim; Jung Yee Mun; Young Jin Chun; Kyung Hee Choi; Sung Wook Ham; Mie Young Kim

2003-01-01

16

Modulation of basophils' degranulation and allergy-related enzymes by monomeric and dimeric naphthoquinones.  

PubMed

Allergic disorders are characterized by an abnormal immune response towards non-infectious substances, being associated with life quality reduction and potential life-threatening reactions. The increasing prevalence of allergic disorders demands for new and effective anti-allergic treatments. Here we test the anti-allergic potential of monomeric (juglone, menadione, naphthazarin, plumbagin) and dimeric (diospyrin and diosquinone) naphthoquinones. Inhibition of RBL-2H3 rat basophils' degranulation by naphthoquinones was assessed using two complementary stimuli: IgE/antigen and calcium ionophore A23187. Additionally, we tested for the inhibition of leukotrienes production in IgE/antigen-stimulated cells, and studied hyaluronidase and lipoxidase inhibition by naphthoquinones in cell-free assays. Naphthazarin (0.1 µM) decreased degranulation induced by IgE/antigen but not A23187, suggesting a mechanism upstream of the calcium increase, unlike diospyrin (10 µM) that reduced degranulation in A23187-stimulated cells. Naphthoquinones were weak hyaluronidase inhibitors, but all inhibited soybean lipoxidase with the most lipophilic diospyrin, diosquinone and menadione being the most potent, thus suggesting a mechanism of competition with natural lipophilic substrates. Menadione was the only naphthoquinone reducing leukotriene C4 production, with a maximal effect at 5 µM. This work expands the current knowledge on the biological properties of naphthoquinones, highlighting naphthazarin, diospyrin and menadione as potential lead compounds for structural modification in the process of improving and developing novel anti-allergic drugs. PMID:24587235

Pinho, Brígida R; Sousa, Carla; Valentão, Patrícia; Oliveira, Jorge M A; Andrade, Paula B

2014-01-01

17

Modulation of Basophils' Degranulation and Allergy-Related Enzymes by Monomeric and Dimeric Naphthoquinones  

PubMed Central

Allergic disorders are characterized by an abnormal immune response towards non-infectious substances, being associated with life quality reduction and potential life-threatening reactions. The increasing prevalence of allergic disorders demands for new and effective anti-allergic treatments. Here we test the anti-allergic potential of monomeric (juglone, menadione, naphthazarin, plumbagin) and dimeric (diospyrin and diosquinone) naphthoquinones. Inhibition of RBL-2H3 rat basophils' degranulation by naphthoquinones was assessed using two complementary stimuli: IgE/antigen and calcium ionophore A23187. Additionally, we tested for the inhibition of leukotrienes production in IgE/antigen-stimulated cells, and studied hyaluronidase and lipoxidase inhibition by naphthoquinones in cell-free assays. Naphthazarin (0.1 µM) decreased degranulation induced by IgE/antigen but not A23187, suggesting a mechanism upstream of the calcium increase, unlike diospyrin (10 µM) that reduced degranulation in A23187-stimulated cells. Naphthoquinones were weak hyaluronidase inhibitors, but all inhibited soybean lipoxidase with the most lipophilic diospyrin, diosquinone and menadione being the most potent, thus suggesting a mechanism of competition with natural lipophilic substrates. Menadione was the only naphthoquinone reducing leukotriene C4 production, with a maximal effect at 5 µM. This work expands the current knowledge on the biological properties of naphthoquinones, highlighting naphthazarin, diospyrin and menadione as potential lead compounds for structural modification in the process of improving and developing novel anti-allergic drugs. PMID:24587235

Pinho, Brigida R.; Sousa, Carla; Valentao, Patricia; Oliveira, Jorge M. A.; Andrade, Paula B.

2014-01-01

18

MEASUREMENT OF HEMOGLOBIN AND ALBUMIN ADDUCTS OF NAPHTHALENE-1,2-OXIDE, 1,2-NAPHTHOQUINONE AND 1,4-NAPHTHOQUINONE AFTER ADMINISTRATION OF NAPHTHALENE TO F344 RATS  

EPA Science Inventory

Naphthalene-1,2-oxide (NPO), 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ) are the major metabolites of naphthalene that are thought to be responsible for the cytotoxicity and genotoxicity of this chemical. We measured cysteinyl adducts of these metabolites in ...

19

Molluscicidal activity of 2-hydroxy-[1,4]naphthoquinone and derivatives.  

PubMed

The toxic profile of lawsone (2-hydroxy-[1,4]naphthoquinone) and a series of [1,4]naphthoquinone derivatives was evaluated against the brine shrimp Artemia salina and against the mollusk Biomphalaria glabrata, the main transmitting vector of schistosomiasis in Brazil. Of the seventeen compounds tested nine fell below the threshold of 100 microg/mL set for potential molluscicidal activity by the World Health Organization. As a general rule derivatives with non-polar substituents presented the highest molluscicidal activities. These substances showed significant toxicity in A. salina lethality bioassay. PMID:18506259

Camara, Celso A; Silva, Tania M S; da-Silva, Thiago G; Martins, Rodrigo M; Barbosa, Ticiano P; Pinto, Angelo C; Vargas, Maria D

2008-06-01

20

Cytotoxicity of new n-butylamino and sulfur-containing derivatives of polyfluorinated 1,4-naphthoquinone.  

PubMed

Four new n-butylamino and two sulfur-containing derivatives of polyfluoro-1,4-naphthoquinone were synthesized and their mutagenic and antioxidant properties in Salmonella cells, as well as the cytotoxicity in human myeloma (RPMI 8226), human mammary adenocarcinoma (MCF-7), mouse fibroblasts (LMTK) and primary mouse fibroblast cells (PMF) were studied. 2-n-Butylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (1) showed efficient inhibition of the growth of the tumor cells. 2,8-Di-(n-butyl-amino)-3,5,6,7-tetrafluoro-1,4-naphthoquinone (2) had significantly less growth-inhibiting properties, while 2,6-di-(n-butylamino)-3,5,7,8-tetrafluoro-1,4-naphthoquinone (3) and 2,6,8-tri-(n-butylamino)-3,5,7-tetrafluoro-1,4-naphthoquinone (4), demonstrated very low cytotoxicity. Compounds 1 and 2 were remarkably less cytotoxic while compound 3 and 4 were not cytotoxic toward LMTK and PMF cells as compared with tumor human cell lines. Cytotoxicity of 2-(2'-methylthioethyl)amino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (5) and (2,2'-dithiodi-2)-3,5,6,7,8-pentafluoro-1,4-naphthoquinone-2-ylamino)ethan (6) toward mammalian cells was compared with that for compounds 1 and 2. PMID:19883955

Zakharova, Ol'ga A; Goryunov, Leonid I; Troshkova, Nadezhda M; Ovchinnikova, Ludmila P; Shteingarts, Vitalij D; Nevinsky, Georgy A

2010-01-01

21

Dynamic quenching study of 2-amino-3-bromo-1,4-naphthoquinone by titanium dioxide nano particles in solution (methanol)  

NASA Astrophysics Data System (ADS)

The dependence of fluorescence emission of 2-amino-3-bromo-1,4-naphthoquinone on titanium dioxide (TiO2) in methanol has been investigated. The increase in TiO2 concentration causes a decrease in the fluorescence intensity of 2-amino-3-bromo-1,4-naphthoquinone. A linear Stern-Volmer plot in this study indicates the presence of dynamic quenching. The quenching and association constants have been calculated. The quenching process is due to the electron transfer from 2-amino-3-bromo-1,4-naphthoquinone to TiO2.

Pushpam, S.; Kottaisamy, M.; Ramakrishnan, V.

2013-10-01

22

Parameters determining the relative efficacy of hydroxy-naphthoquinone inhibitors of the cytochrome bc1 complex  

E-print Network

of the cytochrome bc1 complex that bind to the ubiquinol oxidation site between cytochrome b and the iron) that binds tightly and competitively to the ubi- quinol oxidation site of the cytochrome bc1 complex [1Parameters determining the relative efficacy of hydroxy-naphthoquinone inhibitors of the cytochrome

Trumpower, Bernard L.

23

The Synthesis of 2-acetyl-1,4-naphthoquinone: A Multi-step Synthesis.  

ERIC Educational Resources Information Center

Outlines 2 procedures for synthesizing 2-acetyl-1,4-naphthoquinone to compare relative merits of the two pathways. The major objective of the exercise is to demonstrate that certain factors should be considered when selecting a pathway for synthesis including availability of starting materials, cost of reagents, number of steps involved,…

Green, Ivan R.

1982-01-01

24

Facile Synthesis of Naphthoquinone Spiroketals by Diastereoselective Oxidative [3 + 2] Cycloaddition  

PubMed Central

A highly selective oxidative [3 + 2] cycloaddition of chiral enol ethers and hydroxynaphthoquinone is described. This convergent strategy is amenable to an enantioselective synthesis of ?-rubromycin and related naphthoquinone spiroketals. Several compounds were found to inhibit DNA-polymerase and telomerase in a manner resembling ?-rubromycin and ?-rubromycin. PMID:18044909

Wu, Kun-Liang; Wilkinson, Stephanie; Reich, Norbert O.; Pettus, Thomas R. R.

2008-01-01

25

Selective binding of naphthoquinone derivatives to serum albumin proteins and their effects on cytotoxicity.  

PubMed

Naphthoquinone derivatives such as lapachol, plumbagin, dichloroallyl lawsone show anticancer activity and generally cytotoxicity measurements are carried out in presence of bovine serum albumin; so understanding on the ability of serum albumin binding with such derivatives are essential. We have investigated cytotoxicity and serum albumin binding of a series of structurally related naphthoquinone derivatives. Substrate dependency and high selectivity in binding of naphthoquinone tethered carboxylic acids or pyridines with bovine serum albumin (BSA) and human serum albumin (HSA) are observed. For example, the binding constant of BSA with 3-(1,4-dihydro-2-methyl-1,4-dioxonaphthalen-3yl-thio)propanoic acid is ?594 times higher than 3-(1,4-dioxo-1,4-dihydronaphthalen-2-yl-amino)benzoic acid; whereas 4-(1,4-dioxo-1,4-dihydronaphthalen-2-yl-amino)benzoic acid shows ?367 times higher binding constant than the latter compound. The BSA weakly bind to pyridine tethered naphthoquinones, whereas HSA does not binds with them. The binding constant of HSA with 2-(1,4-dihydro-2-methyl-1,4-dioxonaphthalene-3-ylthio)benzoic acid is 134 times higher than the HSA binding constant with 2,2'-(1,4-dihydro-1,4-dioxo-naphthalen-2,3-diylthio)dipropanoic acid. Among the naphthoquinone carboxylic acids, the 3-(1,4-dioxo-1,4-dihydronaphthalen-2-yl-amino)benzoic acid binds selectively to BSA, but it does not bind to HSA. The 2-hydroxybenzoic acid or 4-mercaptobenzoic acid strongly binds to BSA. The binding of BSA with 4-hydroxybenzoic acid or 2-mercaptobenzoic acid are insignificant. We have not observed clear relationships of structure of naphthoquinone derivatives versus serum albumin binding, but could identify the compound having the best IC50 values of cytotoxicity among the twelve naphthoquinone compounds. The compound 3-(1,2-dihydro-1,2-dioxonaphthalen-4-yl-thio)propanoic acid in four cancer cell lines has IC50 values in the range 2.7-7.6?M. This compound also has optimum binding constant with BSA (35.042×10(3)Lmol(-1)) or HSA (21.427×10(3)Lmol(-1)). The cytotoxicity values of the compounds were influenced by concentration of BSA. PMID:24560625

Jali, Bigyan R; Kuang, Yuting; Neamati, Nouri; Baruah, Jubaraj B

2014-05-01

26

The Naphthoquinone Diospyrin Is an Inhibitor of DNA Gyrase with a Novel Mechanism of Action*  

PubMed Central

Tuberculosis and other bacterial diseases represent a significant threat to human health. The DNA topoisomerases are excellent targets for chemotherapy, and DNA gyrase in particular is a well-validated target for antibacterial agents. Naphthoquinones (e.g. diospyrin and 7-methyljuglone) have been shown to have therapeutic potential, particularly against Mycobacterium tuberculosis. We have found that these compounds are inhibitors of the supercoiling reaction catalyzed by M. tuberculosis gyrase and other gyrases. Our evidence strongly suggests that the compounds bind to the N-terminal domain of GyrB, which contains the ATPase active site, but are not competitive inhibitors of the ATPase reaction. We propose that naphthoquinones bind to GyrB at a novel site close to the ATPase site. This novel mode of action could be exploited to develop new antibacterial agents. PMID:23275348

Karkare, Shantanu; Chung, Terence T. H.; Collin, Frederic; Mitchenall, Lesley A.; McKay, Adam R.; Greive, Sandra J.; Meyer, Jacobus J. M.; Lall, Namrita; Maxwell, Anthony

2013-01-01

27

Increased production of naphthoquinones in Impatiens balsamina root cultures by elicitation with methyl jasmonate.  

PubMed

Impatiens balsamina root cultures were treated with yeast extract (YE), Candida albicans homogenate (CAH), Trichophyton rubrum homogenate (TRH), chitosan (CHI) and methyl jasmonate (MJ). Different elicitors, depending on concentrations used exerted differential effects on the production of the three main naphthoquinones, lawsone (2-hydroxy-1,4-naphthoquinone), lawsone methyl ether and methylene-3,3'-bilawsone. Treatment with MJ (400microM) was capable of increasing production of lawsone, and lawsone methyl ether up to 8.6- and 11.3-fold higher, respectively, compared to the level in untreated cultures. Treatment of 21-day-old root cultures with 300microM MJ for 36h resulted in the production of 10.0, 0.78 and 0.23mg/g DW of lawsone, its methyl ether and methylene-3,3'-bilawsone, respectively. Such levels are sufficient for commercial production. PMID:20620051

Sakunphueak, Athip; Panichayupakaranant, Pharkphoom

2010-11-01

28

Multiple optical properties of a naphthoquinone pigment: 2-methyl-3-(hydroxyphenylthio)-1,4-naphthalenedione.  

PubMed

Naphthoquinone pigments 2-methyl-3-(4- or 2-hydroxyphenylthio)-1,4-naphthalenedione show characteristic optical properties in solution and in the solid state. The position of the OH group in the pigment leads to varied optical properties, including a characteristic colour, in the solid state. The pigment with a 2-OH substituent displays solvatochromism in solution, and that with a 4-OH substituent displays optical chirality in the solid state. PMID:25178051

Akiyama, Hirotaka; Inoue, Takafumi; Tajima, Nobuo; Kuroda, Reiko; Imai, Yoshitane

2014-09-24

29

A Chemical Genetic Screen for Modulators of Asymmetrical 2,2'Dimeric Naphthoquinones Cytotoxicity in Yeast  

Microsoft Academic Search

BackgroundDimeric naphthoquinones (BiQ) were originally synthesized as a new class of HIV integrase inhibitors but have shown integrase-independent cytotoxicity in acute lymphoblastic leukemia cell lines suggesting their use as potential anti-neoplastic agents. The mechanism of this cytotoxicity is unknown. In order to gain insight into the mode of action of binaphthoquinones we performed a systematic high-throughput screen in a yeast

Ashkan Emadi; Ashley E. Ross; Kathleen M. Cowan; Yolanda M. Fortenberry; Milena Vuica-Ross; Xuewen Pan

2010-01-01

30

Synthetic 1,4-Pyran Naphthoquinones Are Potent Inhibitors of Dengue Virus Replication  

PubMed Central

Dengue virus infection is a serious public health problem in endemic areas of the world where 2.5 billion people live. Clinical manifestations of the Dengue infection range from a mild fever to fatal cases of hemorrhagic fever. Although being the most rapidly spreading mosquito-borne viral infection in the world, until now no strategies are available for effective prevention or control of Dengue infection. In this scenario, the development of compounds that specifically inhibit viral replication with minimal effects to the human hosts will have a substantial effect in minimizing the symptoms of the disease and help to prevent viral transmission in the affected population. The aim of this study was to screen compounds with potential activity against dengue virus from a library of synthetic naphthoquinones. Several 1,2- and 1,4-pyran naphthoquinones were synthesized by a three-component reaction of lawsone, aldehyde (formaldehyde or arylaldehydes) and different dienophiles adequately substituted. These compounds were tested for the ability to inhibit the ATPase activity of the viral NS3 enzyme in in vitro assays and the replication of dengue virus in cultured cells. We have identified two 1,4-pyran naphthoquinones, which inhibited dengue virus replication in mammal cells by 99.0% and three others that reduced the dengue virus ATPase activity of NS3 by two-fold in in vitro assays. PMID:24376541

da Costa, Emmerson C. B.; Amorim, Raquel; da Silva, Fernando C.; Rocha, David R.; Papa, Michelle P.; de Arruda, Luciana B.; Mohana-Borges, Ronaldo; Ferreira, Vitor F.; Tanuri, Amilcar

2013-01-01

31

Antifungal activity of synthetic naphthoquinones against dermatophytes and opportunistic fungi: preliminary mechanism-of-action tests.  

PubMed

This study evaluated the antifungal activities of synthetic naphthoquinones against opportunistic and dermatophytic fungi and their preliminary mechanisms of action. The minimum inhibitory concentrations (MICs) of four synthetic naphthoquinones for 89 microorganisms, including opportunistic yeast agents, dermatophytes and opportunistic filamentous fungi, were determined. The compound that exhibited the best activity was assessed for its action against the cell wall (sorbitol test), for interference associated with ergosterol interaction, for osmotic balance (K+ efflux) and for membrane leakage of substances that absorb at the wavelength of 260 nm. All tested naphthoquinones exhibited antifungal activity, and compound IVS320 (3a,10b-dihydro-1H-cyclopenta [b] naphtho [2,3-d] furan-5,10-dione)-dione) demonstrated the lowest MICs across the tested species. The MIC of IVS320 was particularly low for dermatophytes (values ranging from 5-28 ?g/mL) and Cryptococcus spp. (3-5 ?g/mL). In preliminary mechanism-of-action tests, IVS320 did not alter the fungal cell wall but did cause problems in terms of cell membrane permeability (efflux of K+ and leakage of substances that absorb at 260 nm). This last effect was unrelated to ergosterol interactions with the membrane. PMID:24998949

Ferreira, Maria do Perpetuo Socorro Borges Carriço; Cardoso, Mariana Filomena do Carmo; da Silva, Fernando de Carvalho; Ferreira, Vitor Francisco; Lima, Emerson Silva; Souza, João Vicente Braga

2014-01-01

32

Antifungal activity of synthetic naphthoquinones against dermatophytes and opportunistic fungi: preliminary mechanism-of-action tests  

PubMed Central

This study evaluated the antifungal activities of synthetic naphthoquinones against opportunistic and dermatophytic fungi and their preliminary mechanisms of action. The minimum inhibitory concentrations (MICs) of four synthetic naphthoquinones for 89 microorganisms, including opportunistic yeast agents, dermatophytes and opportunistic filamentous fungi, were determined. The compound that exhibited the best activity was assessed for its action against the cell wall (sorbitol test), for interference associated with ergosterol interaction, for osmotic balance (K+ efflux) and for membrane leakage of substances that absorb at the wavelength of 260 nm. All tested naphthoquinones exhibited antifungal activity, and compound IVS320 (3a,10b-dihydro-1H-cyclopenta [b] naphtho [2,3-d] furan-5,10-dione)-dione) demonstrated the lowest MICs across the tested species. The MIC of IVS320 was particularly low for dermatophytes (values ranging from 5–28 ?g/mL) and Cryptococcus spp. (3–5 ?g/mL). In preliminary mechanism-of-action tests, IVS320 did not alter the fungal cell wall but did cause problems in terms of cell membrane permeability (efflux of K+ and leakage of substances that absorb at 260 nm). This last effect was unrelated to ergosterol interactions with the membrane. PMID:24998949

2014-01-01

33

2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone(TM) therapy  

PubMed Central

Apatone™, a combination of menadione (2-methyl-1,4-naphthoquinone, VK3) and ascorbic acid (vitamin C, VC) is a new strategy for cancer treatment. Part of its effect on tumor cells is related to the cellular pro-oxidative imbalance provoked by the generation of hydrogen peroxide (H2O2) through naphthoquinone redox cycling. In this study, we attempted to find new naphthoquinone derivatives that would increase the efficiency of H2O2 production, thereby potentially increasing its efficacy for cancer treatment. The presence of an electron-withdrawing group in the naphthoquinone moiety had a direct effect on the efficiency of H2O2 production. The compound 2-bromo-1,4-naphthoquinone (BrQ), in which the bromine atom substituted the methyl group in VK3, was approximately 10- and 19-fold more efficient than VK3 in terms of oxygen consumption and H2O2 production, respectively. The ratio [H2O2]produced / [naphthoquinone]consumed was 68 ± 11 and 5.8 ± 0.2 (µM/µM) for BrQ and VK3, respectively, indicating a higher efficacy of BrQ as a catalyst for the autoxidation of ascorbic acid. Both VK3 and BrQ reacted with glutathione (GSH), but BrQ was the more effective substrate. Part of GSH was incorporated into the naphthoquinone, producing a nucleophilic substitution product (Q-SG). The depletion of BrQ by GSH did not prevent its redox capacity since Q-SG was also able to catalyze the production of reactive oxygen species. VK3/VC has already been submitted to clinical trials for the treatment of prostate cancer and has demonstrated promising results. However, replacement of VK3 with BrQ will open new lines of investigation regarding this approach to cancer treatment. PMID:22584645

Graciani, F.S.; Ximenes, V.F.

2012-01-01

34

Anomalous Appearance of ?[C(2)=C(3)] Frequencies in IR Spectra of 1,4-Naphthoquinone Hydroxy Derivatives  

NASA Astrophysics Data System (ADS)

Absorption bands in the carbonyl range 1750-1500 cm-1 of the IR spectrum of 2,3-dihydroxy-1,4-naphthoquinone and some of its derivatives were assigned based on calculations of normal mode frequencies using the B3LYP/cc-pVTZ method for isolated molecules and the polarized continuum model taking into account the influence of weakly and moderately polar solvents (CCl4, CDCl3, and CH2Cl2). It was shown that the frequency of the quinone C(2)=C(3) stretching vibration for 2,3-OH- and 2,5,8-OH-1,4-naphthoquinones (2-OH-naphthazarins) was 50-60 cm-1 higher than that of the carbonyl stretching vibration. The frequency difference reached 100 cm-1 for 2,3,5,8-OH-1,4-naphthoquinones (2,3-OH-naphthazarins).

Glazunov, V. P.; Berdyshev, D. V.

2014-09-01

35

Comparison of the cytotoxic effect of lapachol, ?-lapachone and pentacyclic 1,4-naphthoquinones on human leukemic cells  

Microsoft Academic Search

Summary  The pentacyclic 1,4-naphthoquinones 1a–d were cytotoxic (IC50???2–7 ?M) to human leukemic cell lines K562 (oxidative stress-resistant), Lucena-1 (MDR phenotype) and Daudi. Fresh leukemic\\u000a cells obtained from patients, some with the MDR phenotype, were also sensitive to these compounds. The pentacyclic 1,4-naphthoquinones\\u000a 1a and 1c induced apoptotic cell death in cells from leukemic patients as determined by flow cytometry. Conversely, the cell

Eduardo J. S. Salustiano; Chaquip D. Netto; Renata F. Fernandes; Alcides J. M. da Silva; Thiago S. Bacelar; Carolina P. Castro; Camilla D. Buarque; Raquel C. Maia; Vivian M. Rumjanek; Paulo R. R. Costa

2010-01-01

36

Cyclooxygenase-2 inhibitory 1,4-naphthoquinones from Impatiens balsamina L.  

PubMed

Significant selective cyclooxygenase-2 (COX-2) inhibitory activities were observed for two new 1,4-naphthoquinone sodium salts, sodium 3-hydroxide-2[[sodium 3-hydroxide-1,4-dioxo(2-naphthyl)]ethyl]naphthalene-1,4-dione (impatienolate) (1) and sodium 2-hydroxide-3-(2-hydroxyethyl)naphthalene-1,4-dione (balsaminolate) (2), which were isolated from the corolla of Impatiens balsamina L. (Balsaminaceae). Their structures were elucidated by spectral techniques. Our results offer evidence supporting the use of I. balsamina L. to treat articular rheumatism, pain, and swelling. PMID:12033510

Oku, Hisae; Ishiguro, Kyoko

2002-05-01

37

1,4-Naphthoquinone Cations as Antiplasmodial Agents: Hydroxy-, Acyloxy-, and Alkoxy-Substituted Analogues  

PubMed Central

Cations of hydroxy-substituted 1,4-naphthoquinones were synthesized and evaluated as antiplasmodial agents against Plasmodium falciparum. The atovaquone analogues were found to be inactive as antagonists of parasite growth, which was attributed to ionization of the acidic hydroxyl moiety. Upon modification to an alkoxy substituent, the antiplasmodial activity was restored in the sub-100 nM range. Optimal inhibitors were found to possess IC50 values of 17.4–49.5 nM against heteroresistant P. falciparum W2. PMID:24936235

2012-01-01

38

Effect of inducers of DT-diaphorase on the haemolytic activity and nephrotoxicity of 2-amino-1,4-naphthoquinone in rats.  

PubMed

Reduction of naphthoquinones by DT-diaphorase is often described as a detoxification reaction. This is true for some naphthoquinone derivatives, such as alkyl and di-alkyl naphthoquinones, but the situation with other substances, such as 2-hydroxy-1,4-naphthoquinone, is more complex. In the present study, the effect of several substances that are known to increase tissue activities of DT-diaphorase on the toxicity of 2-amino-1,4-naphthoquinone has been investigated. Like 2-hydroxy-1,4-naphthoquinone, the 2-amino-derivative was found to cause both haemolytic anaemia and renal tubular necrosis in rats. Again like 2-hydroxy-1,4-naphthoquinone, the severity of the haemolysis induced by the 2-amino derivative was increased in animals pre-treated with inducers of DT-diaphorase, but the degree of nephrotoxicity was decreased. With these substances, therefore, DT-diaphorase both activates and detoxifies the quinone, depending on the target organ. It is not possible to generalize with regard to the effects of modulation of tissue levels of DT-diaphorase on naphthoquinone toxicity in vivo, since this may change not only the severity of the toxic effects, but also the target organ specificity. In evaluating the possible therapeutic applications of such compounds, the possibility of toxic effects upon the blood and kidney must be borne in mind. In man, renal damage by compounds such as 2-hydroxy- and 2-amino-1,4-naphthoquinone may be a particular problem, because of the low level of DT-diaphorase in human liver. PMID:16045903

Munday, Rex; Smith, Barry L; Munday, Christine M

2005-08-15

39

Effect of inducers of DT-diaphorase on the toxicity of 2-methyl- and 2-hydroxy-1,4-naphthoquinone to rats.  

PubMed

It has previously been shown that rats pre-treated with butylated hydroxyanisole (BHA), a well-known inducer of the enzyme DT-diaphorase, are protected against the toxic effects of 2-methyl-1,4-naphthoquinone but are made more susceptible to the harmful action of 2-hydroxy-1,4-naphthoquinone. In the present experiments, the effects of BHA have been compared with those of other inducers of DT-diaphorase. Rats were dosed with BHA, butylated hydroxytoluene (BHT), ethoxyquin (EQ), dimethyl fumarate (DMF) or disulfiram (DIS) and then challenged with a toxic dose of the naphthoquinones. All the inducers protected against the haemolytic anaemia induced by 2-methyl-1,4-naphthoquinone in rats, with BHA, BHT and EQ being somewhat more effective than DMF and DIS. A similar order of activity was recorded in the relative ability of these substances to increase hepatic activities of DT-diaphorase, consistent with a role for this enzyme in facilitating conjugation and excretion of this naphthoquinone. In contrast, all the compounds increased the haemolytic activity of 2-hydroxy-1,4-naphthoquinone. DMF and DIS were significantly more effective in this regard than BHA, BHT and EQ. DMF and DIS also caused a much greater increase in levels of DT-diaphorase in the intestine, suggesting that 2-hydroxy-1,4-naphthoquinone is activated by this enzyme in the gut. BHA, BHT and EQ had no effect on the nephrotoxicity of 2-hydroxy-1,4-naphthoquinone, but the severity of the renal lesions was decreased in rats pre-treated with DMF and DIS. The results of the present experiments show that modulation of tissue levels of DT-diaphorase may not only alter the severity of naphthoquinone toxicity in vivo, but may also change the relative toxicity of these substances to different target organs. PMID:10654840

Munday, R; Smith, B L; Munday, C M

1999-12-15

40

Induced production of antifungal naphthoquinones in the pitchers of the carnivorous plant Nepenthes khasiana  

PubMed Central

Nepenthes spp. are carnivorous plants that have developed insect capturing traps, evolved by specific modification of the leaf tips, and are able to utilize insect degradation products as nutritional precursors. A chitin-induced antifungal ability, based on the production and secretion to the trap liquid of droserone and 5-O-methyldroserone, is described here. Such specific secretion uniquely occurred when chitin injection was used as the eliciting agent and probably reflects a certain kind of defence mechanism that has been evolved for protecting the carnivory-based provision of nutritional precursors. The pitcher liquid containing droserone and 5-O-methyldroserone at 3:1 or 4:1 molar ratio, as well as the purified naphthoquinones, exerted an antifungal effect on a wide range of plant and human fungal pathogens. When tested against Candida and Aspergillus spp., the concentrations required for achieving inhibitory and fungicidal effects were significantly lower than those causing cytotoxicity in cells of the human embryonic kidney cell line, 293T. These naturally secreted 1,4-naphthoquinone derivatives, that are assumed to act via semiquinone enhancement of free radical production, may offer a new lead to develop alternative antifungal drugs with reduced selectable pressure for potentially evolved resistance. PMID:20018905

Eilenberg, Haviva; Pnini-Cohen, Smadar; Rahamim, Yocheved; Sionov, Edward; Segal, Esther; Carmeli, Shmuel; Zilberstein, Aviah

2010-01-01

41

Naphthoquinone spiroketals and organic extracts from the endophytic fungus Edenia gomezpompae as potential herbicides.  

PubMed

From the fermentation mycelium of the endophytic fungus Edenia gomezpompae were obtained several phytotoxic compounds including two new members of the naphthoquinone spiroketal family, namely, palmarumycin EG1 (1) and preussomerin EG4 (4). In addition, preussomerins EG1-EG3 (7-9) and palmarumycins CP19 (2), CP17 (3), and CP2 (6), as well as ergosta-4,6,8(14),22-tetraen-3-one (5), were obtained. Compounds 2, 3, and 5 are new to this species. The structures of palmarumycins CP19 (2) and CP17 (3) were unambiguously determined by X-ray analysis. The isolates and mycelium organic extracts from four morphological variants of E. gomezpompae caused significant inhibition of seed germination, root elongation, and seedling respiration of Amaranthus hypochondriacus, Solanum lycopersicum, and Echinochloa crus-galli. The treatments also affected respiration on intact mitochondria isolated from spinach. PMID:24689520

Macías-Rubalcava, Martha L; Ruiz-Velasco Sobrino, M Emma; Meléndez-González, Claudio; Hernández-Ortega, Simón

2014-04-23

42

Naphthalene and Naphthoquinone: Distributions and Human Exposure in the Los Angeles Basin  

NASA Astrophysics Data System (ADS)

Naphthalene is the simplest and most abundant of the polycyclic aromatic hydrocarbons (PAHs). Naphthalene is found primarily in the gas-phase and has been detected in both outdoor and indoor samples. Evaporation from naphthalene-containing products (including gasoline), and during refining operations, are important sources of naphthalene in air. Naphthalene is also emitted during the combustion of fossil fuels and wood, and is a component of vehicle exhaust. Exposure to high concentrations of naphthalene can damage or destroy red blood cells, causing hemolytic anemia. If inhaled over a long period of time, naphthalene may cause kidney and liver damage, skin allergy and dermatitis, cataracts and retinal damage, as well as attack the central nervous system. Naphthalene has been found to cause cancer as a result of inhalation in animal tests. Naphthoquinones are photooxidation products of naphthalene and the potential health effects of exposure to these quinones are a current focus of research. We are developing and applying models that can be used to assess human exposure to naphthalene and its photooxidation products in major air basins such as California South Coast Air Basin (SoCAB). The work utilizes the Surface Meteorology and Ozone Generation (SMOG) airshed model, and the REgional Human EXposure (REHEX) model, including an analysis of individual exposure. We will present and discuss simulations of basin-wide distributions of, and human exposures to, naphthalene and naphthoquinone, with emphasis on the uncertainties in these estimates of atmospheric concentrations and human exposure. Regional modeling of pollutant sources and exposures can lead to cost-effective and optimally health-protective emission control strategies.

Lu, R.; Wu, J.; Turco, R.; Winer, A. M.; Atkinson, R.; Paulson, S.; Arey, J.; Lurmann, F.

2003-12-01

43

The 1,4-naphthoquinone derivative from Pyrola rotundifolia activates AMPK phosphorylation in C2C12 myotubes.  

PubMed

An aqueous ethanol extract of Pyrola rotundifolia L. induced AMP-activated protein kinase (AMPK) phosphorylation in C2C12 myotubes. The bioassay-guided fractionation of the extract led to the isolation a 2-methyl-7-hydroxymethyl-1,4-naphthoquinone, or a 7'-hydroxy-chimaphilin, which showed concentration-dependent AMPK phosphorylation activity at 2.5-20 ?g/ml. At a concentration of 10 ?g/ml (50 ?M), an approximately four-fold increase in the AMPK?(Thr¹?²) phosphorylation level was observed. The stimulatory effect of naphthoquinone on AMPK activity was comparable to that of known compounds found in natural sources that activate the AMPK signaling pathway. PMID:21958969

Ptitsyn, Leonid R; Nomura, Kenzo; Sklyar, Ilya V; Ravcheeva, Anna B

2011-12-01

44

Flow-injection spectrophotometric determination of cyclamate in sweetener products with sodium 1,2-naphthoquinone-4-sulfonate  

Microsoft Academic Search

A method for the determination of cyclamate in sweetener tablets is proposed. The method is based on the conversion of cyclamate to cyclohexylamine and the subsequent reaction with 1,2-naphthoquinone-4-sulfonate, yielding a spectrophotometrically active derivative which is detected at 480nm. The hydrolysis step is performed batch wise by treatment of cyclamate with hydrogen peroxide and hydrochloric acid, while the cyclohexylamine derivatization

Carolina Cabero; Javier Saurina; Santiago Hernández-Cassou

1999-01-01

45

Isolation of three antibacterial naphthoquinones from Plumbago indica roots and development of a validated quantitative HPLC analytical method.  

PubMed

Three naphthoquinones, plumbagin (1), 3,3'-biplumbagin (2) and elliptinone (3), isolated from Plumbago indica roots by antibacterial bioassay-guided isolation, were used as standard markers for quantitative determination. A reversed-phase HPLC method was established for the simultaneous determination of the naphthoquinones in P. indica root extracts. The method utilised a Phenomenex® ODS column (4.6?×?150?mm, 5?µm) at 25°C with a mixture of methanol and 5% aqueous acetic acid (80?:?20 v/v) as the mobile phase at a flow rate of 0.85?mL/min, and UV detection at 260?nm. The parameters of linearity, precision, accuracy specificity and sensitivity of the method were evaluated. The recovery of the method was 98.6-100.6% with good linearity (r (2?)??0.9997) for all three naphthoquinones. A high degree of sensitivity, specificity as well as repeatability and reproducibility (R.S.D. values less than 5%) were also achieved. PMID:22010802

Kaewbumrung, Sermwut; Panichayupakaranant, Pharkphoom

2012-11-01

46

Structure/antileishmanial activity relationship study of naphthoquinones and dependency of the mode of action on the substitution patterns.  

PubMed

A series of naphthoquinones was tested for activity against both extracellular promastigote and intracellular amastigote Leishmania major GFP in vitro. In parallel, the compounds were evaluated for cytotoxic effects against bone marrow-derived macrophages (BMM ?) as a mammalian host cell control. Most of the compounds noticeably inhibited the growth of extracellular parasites (IC (50) 0.5 to 6?µM) and the intracellular survival of L. major GFP amastigotes (IC (50) 1 to 7?µM) when compared with the antileishmanial drug amphotericin B (IC (50) of 2.5 and 0.2?µM, respectively). In general, antiprotozoal activity and host cell cytotoxicity seemed to increase in parallel. Conspicuously, the cytotoxic effect was less pronounced on infected host cells when compared with that on noninfected cells. Concerning structure/activity relationships for the tested naphthoquinones, some interesting structural features emerged from this study. Introduction of a methyl or methoxyl group at C-2 of the parent 1,4-naphthoquinone slightly increased the antileishmanial activity against clinically relevant amastigotes, while the presence of a hydroxyl function in this position dramatically reduced the effectiveness. In contrast, hydroxylation at C-5 and dihydroxy substitution at C-5 and C-8 significantly enhanced the antiprotozoal activity. Similarly, the presence of a side chain hydroxyl group PERI to a carbonyl function as represented in the series of shikonin/alkannin derivatives increased the activity when compared with substituted analogs. Within the series of naphthoquinones tested, the dimeric mixture of vaforhizin and isovaforhizin showed the highest activity IN VITRO against the clinically relevant intracellular amastigote with an IC (50) of 1.1?µM. With IC (50) values mostly in the range of 1-3?µM, the shikonin/alkannin derivatives proved to be similarly considerably leishmanicidal. None of the compounds tested was capable to induce NO production known to play a crucial role in the host resistance against intracellular pathogens, excluding activation of microbicidal mechanisms in macrophages. The mode of action apparently depended on the substitution pattern, associated with the electrophilicity of the naphthoquinone or the efficiency of redox cycling. Conspicuously, members oxygenated in the quinone ring proved to be leishmanicidal when coincubated with glutathione, while the majority of the remaining compounds lost activity. PMID:21800278

Ali, Ahmad; Assimopoulou, Andreana Nikolaos; Papageorgiou, Vassilios Peter; Kolodziej, Herbert

2011-12-01

47

Naphthoquinones from Catalpa ovata and their inhibitory effects on the production of nitric oxide.  

PubMed

Bioassay-guided fractionation of a CH2Cl2-soluble fraction of the stems of Catalpa ovata led to isolation of a new naphthoquinone, 4-hydroxy-2-(2-methoxy-3-hydroxy-3-methyl-but-1-enyl)-4-hydro-1H-naphthalen-1-one (10), together with nine known compounds, catalponol (1), catalponone (2), catalpalactone (3), alpha-lapachone (4), 9-hydroxy-alpha-lapachone (5), 4,9-dihydroxy-alpha-lapachone (6), 9-methoxy-alpha-lapachone (7), 4-oxo-alpha-lapachone (8), and 9-methoxy-4-oxo-alpha-lapachone (9). The structures were elucidated on the basis of spectroscopic analyses. The inhibitory effects of these isolates on lipopolysaccharide-induced NO synthesis in RAW 264.7 cells were evaluated. Among them, catapalactone (3), 9-hydroxy-alpha-lapachone (5) and 4,9-dihydroxy-alpha-lapachone (6) exhibited potent inhibitory effects, with IC(50) values of 9.80, 4.64 and 2.73 microM, respectively. PMID:20361302

Park, Byeong Min; Hong, Seong Su; Lee, Chul; Lee, Moon Soon; Kang, Shin Jung; Shin, Yu Su; Jung, Jae-Kyung; Hong, Jin Tae; Kim, Youngsoo; Lee, Mi Kyeong; Hwang, Bang Yeon

2010-03-01

48

Bactericidal Action of 2-Hydroxy-3-(Cyclohexylpropyl)-1,4-Naphthoquinone on Bacillus megaterium  

PubMed Central

The antimalarial drug, 2-hydroxy-3-(cyclohexylpropyl)-1,4-naphthoquinone (NQ), at concentrations of approximately 10?5m (3 ?g/ml), was bactericidal for the gram-positive bacterium, Bacillus megaterium. Only a few other gram-positive bacteria were sensitive to this drug. All growth inhibitory concentrations of NQ were also bactericidal for B. megaterium, and even resting suspensions of cells were killed. The incorporation of radioactive-labeled leucine, thymidine, uracil, and diaminopimelic acid into protein, deoxyribonucleic acid, ribonucleic acid, and the cell wall polymer was arrested immediately and completely upon addition of NQ to cultures in exponential growth. NQ produced a delayed effect on aerobic respiration and no change in the rate of oxygen consumption was observed at a time when all major biosyntheses had failed. 3H-NQ was demonstrated to bind strongly and preferentially to the bacterial cell membrane. This simultaneous shutdown of all major categories of in vivo macromolecular syntheses points to an effect of NQ upon membrane-centered energy supplying reactions or transport of essential nutrients, or both. PMID:5000306

Olenick, John G.; Cook, Thomas M.; Hahn, Fred E.

1971-01-01

49

Cytotoxicity of synthesized 1,4-naphthoquinone analogues on selected human cancer cell lines.  

PubMed

In an effort to establish new candidates with enhanced anticancer activity of 5-hydroxy-7-methyl-1,4-naphthoquinone scaffold (7-methyljuglone) previously isolated from the root extract of Euclea natalensis, a series of 7-methyljuglone derivatives have been synthesized and assessed for cytotoxicity on selected human cancer lines. These compounds were screened in vitro for anticancer activity on MCF-7, HeLa, SNO and DU145 human cancer cell lines by MTT assay. Most of them exhibited significant toxicity on cancer cell lines with lower IC50 values. The most potent derivative (19) exhibited the toxicity on HeLa and DU145 cell lines with IC50 value of 5.3 and 6.8?M followed by compound (5) with IC50 value of 10.1 and 9.3?M, respectively. Structure-activity relationship reveals that the fluoro substituents at position C-8 while hydroxyl substituents at C-2 and C-5 positions played an important role in toxicity. PMID:25059501

Kishore, Navneet; Binneman, Brigitte; Mahapatra, Anita; van de Venter, Maryna; du Plessis-Stoman, Debbie; Boukes, Gerhardt; Houghton, Peter; Marion Meyer, J J; Lall, Namrita

2014-09-01

50

Synthesis and SAR study of novel anticancer and antimicrobial naphthoquinone amide derivatives.  

PubMed

A series of novel naphthoquinone amide derivatives of the bioactive quinones, plumbagin, juglone, menadione and lawsone, with various amino acids were synthesized. The compounds were characterized by (1)H NMR, (13)C NMR, Mass, IR and elemental analysis. All the compounds were evaluated for their anticancer activity against HeLa and SAS cancer cell lines and 3D-QSAR indicated the presence of electron donating group near sulphur enhanced the activity against HeLa cells. Among the derivatives synthesized, compounds 11f, 10a, 10b and 10g were the most active with IC50 values of 16, 12, 14 and 24.5 ?M, respectively. The analogues were also screened for antimicrobial activity against two human bacterial pathogens, the Gram-positive Methicillin resistant Staphylococcus aureus (MRSA) and the Gram-negative Pseudomonas aeruginosa and a human yeast pathogen, Fluconazole resistant Candida albicans (FRCA). Among the synthesized compounds, 8g, 10g and 11g exhibited maximum antibacterial activity towards MRSA and antifungal activity against FRCA in well diffusion method. PMID:24913712

Sreelatha, Thonthula; Kandhasamy, Subramani; Dinesh, Raghu; Shruthy, Suresh; Shweta, Sinha; Mukesh, Doble; Karunagaran, Devarajan; Balaji, Ravichandran; Mathivanan, Narayanasamy; Perumal, Paramasivan Thirumalai

2014-08-01

51

Sensitive and selective spectrophotometric assay of gabapentin in capsules using sodium 1, 2-naphthoquinone-4-sulfonate.  

PubMed

A simple, sensitive, and selective spectrophotometric method has been developed for the determination of gabapentin (GBP) in capsules. The method is based on the reaction of GBP and sodium 1,2-naphthoquinone-4-sulfonate (NQS) in the presence of Clark and Lubs buffer of pH 11 to form an orange-coloured product which was measured at 495 nm. The parameters that affect the reaction were carefully optimized and under the optimized conditions, linear relationship was obtained in the concentration range of 7.5-75 µg ml(-1) GBP. The molar absorptivity, limits of detection (LOD) and quantification (LOQ) and Sandell sensitivity are also reported. The proposed method was successfully applied to the determination of GBP in capsules with good accuracy and precision and without detectable interference from common excipients. The reliability of the proposed method was further established by parallel determination by the reference method and also by recovery studies. The reaction mechanism is proposed and discussed. PMID:21337720

Abdulrahman, Sameer A M; Basavaiah, Kanakapura

2011-10-01

52

An Efficient Method for Extraction, Separation and Purification of Naphthoquinone Pigments from Lithospermum erythrorhizon Sieb. et Zucc . by SFE and HSCCC  

Microsoft Academic Search

Supercritical fluid extraction was used to extract naphthoquinone pigments from Lithospermum erythrorhizon Sieb. et Zucc. The crude extracts were separated and purified by high-speed counter-current chromatography with light petroleum–ethyl\\u000a acetate–methanol–water (5:5:8:2, v\\/v) as the two-phase solvent system. Three kinds of naphthoquinone pigments including 17.6 mg of ?-hydroxyisovalerylshikonin\\u000a (I), 17.6 mg of acetylshikonin (II), and 19.7 mg of isobutyrylshikonin (III) were obtained from 150 mg

Lei Feng; Haiwei Ji; Hongxia Gu; Decai Wang; Jichun Cui; Renmin Liu; Jing Zhai

2009-01-01

53

The 1,4-naphthoquinone derivative from Pyrola rotundifolia activates AMPK phosphorylation in C2C12 myotubes  

Microsoft Academic Search

An aqueous ethanol extract of Pyrola rotundifolia L. induced AMP-activated protein kinase (AMPK) phosphorylation in C2C12 myotubes. The bioassay-guided fractionation of the extract led to the isolation a 2-methyl-7-hydroxymethyl-1,4-naphthoquinone, or a 7?-hydroxy-chimaphilin, which showed concentration-dependent AMPK phosphorylation activity at 2.5–20?g\\/ml. At a concentration of 10?g\\/ml (50?M), an approximately four-fold increase in the AMPK?(Thr172) phosphorylation level was observed. The stimulatory effect

Leonid R. Ptitsyn; Kenzo Nomura; Ilya V. Sklyar; Anna B. Ravcheeva

54

2-methoxy-1,4-naphthoquinone isolated from Impatiens balsamina in a screening program for activity to inhibit Wnt signaling.  

PubMed

A screening study using a luciferase assay to identify natural products which inhibit Wnt signaling was carried out. The bioassay-guided fractionation of aerial parts of a plant, Impatiens balsamina, led to the isolation of 2-methoxy-1,4-naphthoquinone (1) as an active compound. Compound 1 inhibited the TCF/?-catenin (TOP) transcriptional activity (IC(50) 2.9 µM), while it decreased the transcriptional activity of FOP (mutated TCF-binding site)-transfected cells at >5 µM. PMID:20886301

Mori, Naomi; Toume, Kazufumi; Arai, Midori A; Koyano, Takashi; Kowithayakorn, Thaworn; Ishibashi, Masami

2011-01-01

55

Substituted 3?acyl?2?phenylamino?1,4?naphthoquinones intercalate into DNA and cause genotoxicity through the increased generation of reactive oxygen species culminating in cell death.  

PubMed

Naphthoquinones interact with biological systems by generating reactive oxygen species (ROS) that can damage cancer cells. The cytotoxicity and the antitumor activity of 3?acyl?2?phenylamino?1,4?naphthoquinones (DPB1?DPB9) were evaluated in the MCF7 human breast cancer cell line and in male Ehrlich tumor?bearing Balb/c mice. DPB4 was the most cytotoxic derivative against MCF7 cells (EC50 15 µM) and DPB6 was the least cytotoxic one (EC50 56 µM). The 1,4?naphthoquinone derivatives were able to cause DNA damage and promote DNA fragmentation as shown by the plasmid DNA cleavage assay (FII form). In addition, 1,4?naphthoquinone derivatives possibly interacted with DNA as intercalating agents, which was demonstrated by the changes caused in the fluorescence of the DNA?ethidium bromide complexes. Cell death of MCF7 cells induced by 3?acyl?2?phenylamino?1,4?naphthoquinones was mostly due to apoptosis. The DNA fragmentation and subsequent apoptosis may be correlated to the redox potential of the 1,4?naphthoquinone derivatives that, once present in the cell nucleus, led to the increased generation of ROS. Finally, certain 1,4?naphthoquinone derivatives and particularly DPB4 significantly inhibited the growth of Ehrlich ascites tumors in mice (73%). PMID:24756411

Farias, Mirelle Sifroni; Pich, Claus Tröger; Kviecinski, Maicon Roberto; Bucker, Nádia Cristina Falcão; Felipe, Karina Bettega; Da Silva, Fabiana Ourique; Günther, Tânia Mara Fisher; Correia, João Francisco; Ríos, David; Benites, Julio; Valderrama, Jaime A; Calderon, Pedro Buc; Pedrosa, Rozangela Curi

2014-07-01

56

Genes differentially expressed under naphthoquinone-producing conditions in the entomopathogenic fungus Ophiocordyceps unilateralis.  

PubMed

The ant-pathogenic fungus Ophiocordyceps unilateralis BCC1869 produces six naphthoquinone (NQ) derivatives. These NQs can be found in fungal-infected ants or produced in culture. Also, the NQs have antibacterial, anticancer, and antimalarial activities and are red pigments with potential for use as natural colorants. Suppressive subtractive hybridization identified genes that were expressed under NQ-producing conditions but not under nonproducing conditions. On potato dextrose agar, the mycelia produced red pigments and secreted them into the medium and as droplets on top of the colony. High-performance liquid chromatography analysis indicated that the red pigment was predominantly erythrostominone with small amounts of its derivatives. For suppressive subtractive hybridization, the cDNA from O. unilateralis cultures on complete medium agar cultures (lacking NQs) were subtracted from those on potato dextrose agar (which produce and secrete NQs). Sixty-six unique expressed sequence tags (ESTs) were identified and include five transporter genes, two transcriptional regulator genes, and several genes in secondary metabolism and biodegradation. The transporter genes include an ATP-binding cassette transporter gene OuAtr1 and a major facilitator superfamily transporter gene OuMfs1. Expression of selected ESTs was further validated using quantitative reverse transcription PCR. Gene expression result indicates that OuAtr1 and OuMfs1 were dramatically upregulated (136- and 29-fold increase, respectively) during the NQ-producing stage compared with the NQ-nonproducing stage. Upregulation of other genes was also detected. This EST collection represents the first group of genes identified from this potential biocontrol agent and includes candidate genes for production and secretion of the red NQs. Roles of these genes could be further determined using a functional analysis. PMID:21823977

Amnuaykanjanasin, Alongkorn; Panchanawaporn, Sarocha; Chutrakul, Chanikul; Tanticharoen, Morakot

2011-08-01

57

Naphthoquinone-tyrptophan reduces neurotoxic A?*56 levels and improves cognition in Alzheimer's disease animal model.  

PubMed

An increasing body of evidence indicates a role for oligomers of the amyloid-? peptide (A?) in the neurotoxicity of this peptide and the pathology of Alzheimer's disease (AD). Several neurotoxic oligomeric forms of A? have been noted ranging from the larger Amyloid ?-Derived Diffusible Ligands (ADDLs) to smaller trimers and dimers of A?. More recently a dodecameric form of A? with a 56 kDa molecular weight, denoted A?*56, was shown to cause memory impairment in AD model mice. Here, we present for the first time a potential therapeutic strategy for AD that targets the early stages in the formation of neurotoxic A?*56 oligomers using a modified quinone-Tryptophan small molecule N-(3-chloro-1,4-dihydro-1,4-dioxo-2-naphthalenyl)-L-Tryptophan (Cl-NQTrp). Using NMR spectroscopy we show that this compound binds the aromatic recognition core of A? and prevents the formation of oligomers. We assessed the effect of Cl-NQTrp in vivo in transgenic flies expressing A?(1-42) in their nervous system. When these flies were fed with Cl-NQTrp a marked alleviation of their A?-engendered reduced life span and defective locomotion was observed. Finally, intraperitoneal injection of Cl-NQTrp into an aggressive AD mouse model reduced the level of the A?*56 species in their brain and reversed their cognitive defects. Further experiments should assess whether this is a direct effect of the drug in the brain or an indirect peripheral effect. This is the first demonstration that targeted reduction of A?*56 results in amelioration of AD symptoms. This second generation of tryptophan-modified naphthoquinones could therefore serve as potent disease modifying therapeutic for AD. PMID:22449754

Scherzer-Attali, R; Farfara, D; Cooper, I; Levin, A; Ben-Romano, T; Trudler, D; Vientrov, M; Shaltiel-Karyo, R; Shalev, D E; Segev-Amzaleg, N; Gazit, E; Segal, D; Frenkel, D

2012-06-01

58

Sequential synthesis of amino-1,4-naphthoquinone-appended triazoles and triazole-chromene hybrids and their antimycobacterial evaluation.  

PubMed

A general method for the synthesis of a library of hitherto unreported amino-1,4-naphthoquinone-appended triazoles was accomplished via a sequential three-component reaction of substituted N-propargylaminonaphthoquinones with variously substituted alkyl bromides/2-bromonaphthalene-1,4-dione and sodium azide in the presence of Et3N/CuI in water. Aminonaphthoquinone-appended iminochromene-triazole hybrid heterocycles were also synthesized from the amino-1,4-naphthoquinone-appended-1,2,3-triazolylacetonitriles. All the triazole hybrids were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Among the triazoles, 2-(((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)(4-(trifluoromethyl)phenyl)amino)naphthalene-1,4-dione (7d) emerged as the most active one with IC50 = 1.87 ?M, being more potent than the anti-TB drugs, cycloserine (6 times), pyrimethamine (20 times) and equipotent as the drug ethambutol (IC50 < 1.56 ?M). PMID:25129868

Devi Bala, Balasubramanian; Muthusaravanan, Sivasubramanian; Choon, Tan Soo; Ashraf Ali, Mohamed; Perumal, Subbu

2014-10-01

59

Naphthoquinone-mediated inhibition of lysine acetyltransferase KAT3B/p300, basis for non-toxic inhibitor synthesis.  

PubMed

Hydroxynaphthoquinone-based inhibitors of the lysine acetyltransferase KAT3B (p300), such as plumbagin, are relatively toxic. Here, we report that free thiol reactivity and redox cycling properties greatly contribute to the toxicity of plumbagin. A reactive 3rd position in the naphthoquinone derivatives is essential for thiol reactivity and enhances redox cycling. Using this clue, we synthesized PTK1, harboring a methyl substitution at the 3rd position of plumbagin. This molecule loses its thiol reactivity completely and its redox cycling ability to a lesser extent. Mechanistically, non-competitive, reversible binding of the inhibitor to the lysine acetyltransferase (KAT) domain of p300 is largely responsible for the acetyltransferase inhibition. Remarkably, the modified inhibitor PTK1 was a nearly non-toxic inhibitor of p300. The present report elucidates the mechanism of acetyltransferase activity inhibition by 1,4-naphthoquinones, which involves redox cycling and nucleophilic adduct formation, and it suggests possible routes of synthesis of the non-toxic inhibitor. PMID:24469461

Vasudevarao, Mohankrishna Dalvoy; Mizar, Pushpak; Kumari, Sujata; Mandal, Somnath; Siddhanta, Soumik; Swamy, Mahadeva M M; Kaypee, Stephanie; Kodihalli, Ravindra C; Banerjee, Amrita; Naryana, Chandrabhas; Dasgupta, Dipak; Kundu, Tapas K

2014-03-14

60

Solid-phase organic synthesis of 2-tridecanyl-1,4-naphthoquinone and 2-tridecanyl-1,4-naphthodiol that form redox-active micelles and vesicles.  

PubMed

The solid-phase synthesis of new amphiphilic compounds is reported. It is based on a newly designed 1,4-naphthoquinone derivative that contains polar and nonpolar groups and self-assembles into micelles or vesicles in water depending on the concentration. They also display redox-active properties. PMID:25036816

Bugarin, Alejandro; Martinez, Luis E; Cooke, Peter; Islam, Tadiqul; Noveron, Juan C

2014-10-01

61

The structure and function of quinones in biological solar energy transduction: a cyclic voltammetry, EPR, and hyperfine sub-level correlation (HYSCORE) spectroscopy study of model naphthoquinones.  

PubMed

Quinones function as electron transport cofactors in photosynthesis and cellular respiration. The versatility and functional diversity of quinones is primarily due to the diverse midpoint potentials that are tuned by the substituent effects and interactions with surrounding amino acid residues in the binding site in the protein. In the present study, a library of substituted 1,4-naphthoquinones are analyzed by cyclic voltammetry in both protic and aprotic solvents to determine effects of substituent groups and hydrogen bonds on the midpoint potential. We use continuous-wave electron paramagnetic resonance (EPR) spectroscopy to determine the influence of substituent groups on the electronic properties of the 1,4-naphthoquinone models in an aprotic solvent. The results establish a correlation between the presence of substituent group(s) and the modification of electronic properties and a corresponding shift in the midpoint potential of the naphthoquinone models. Further, we use pulsed EPR spectroscopy to determine the effect of substituent groups on the strength and planarity of the hydrogen bonds of naphthoquinone models in a protic solvent. This study provides support for the tuning of the electronic properties of quinone cofactors by the influence of substituent groups and hydrogen bonding interactions. PMID:23676117

Coates, Christopher S; Ziegler, Jessica; Manz, Katherine; Good, Jacob; Kang, Bernard; Milikisiyants, Sergey; Chatterjee, Ruchira; Hao, Sijie; Golbeck, John H; Lakshmi, K V

2013-06-20

62

2-(Fluoromethyl)-3-phytyl-1,4-naphthoquinone and its 2,3-epoxide. Inhibition of vitamin K epoxide reductase.  

PubMed

2-(Fluoromethyl)-3-phytyl-1,4-naphthoquinone (7) was synthesized from the known compound 2-bromo-3-methyl-1,4-dimethoxynaphthalene by N-bromosuccinimide bromination of the 3-methyl group, conversion to the corresponding 3-fluoromethyl compound with silver fluoride, attachment of the 3-phytyl substitutent via the lithium diaryl cuprate and phytyl bromide, and then silver oxide oxidation to 7. Epoxidation with basic hydrogen peroxide gave the corresponding 2,3-oxide (1) in a very low yield. Compound 1 was not a time-dependent inhibitor of beef liver microsomal vitamin K epoxide reductase, but it was a competitive, reversible inhibitor. It was not possible to determine if 1 was a substrate for the enzyme because the expected product of reduction, namely 7, rapidly decomposed under the assay conditions. PMID:2769684

Silverman, R B; Oliver, J S

1989-09-01

63

1,2Naphthoquinone4-sulphonic acid sodium salt (NQS) as an analytical reagent for the determination pharmaceutical amine by spectrophotometry  

Microsoft Academic Search

Several papers have been presented in recent years regarding the field of application of 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS) as chromogenic reagent for the determination of pharmaceutical amines using spectrophotometry. In this review article, various spectrophotometric methods using NQS as a labeling reagent for determination of pharmaceutical amines are presented. The application of these methods for the determination of drugs

Abdalla Ahmed Elbashir; Abir Abdalla Ahmed; Shazalia M. Ali Ahmed; Hassan Y. Aboul-Enein

2011-01-01

64

A Selective Spectrofluorometric Determination of Micromolar Level of Cyanide in Water Using Naphthoquinone Imidazole Boronic-Based Sensors and a Surfactant Cationic CTAB Micellar System  

Microsoft Academic Search

We developed a new spectrofluorometric method for qualitative and quantitative determination of cyanide in water using the\\u000a incorporation of naphthoquinone imidazole boronic-based sensors (m\\u000a -NQB and p\\u000a -NQB) and a cationic surfactant, certyltrimethyl ammonium bromide (CTAB). This micellar system exhibited great selectivity for\\u000a cyanide detection with an assistance of the cationic surface of micelle. The interaction of boronic acid of

Matinee Jamkratoke; Gamolwan Tumcharern; Thawatchai Tuntulani; Boosayarat Tomapatanaget

2011-01-01

65

Novel spectrophotometric method for determination of some macrolide antibiotics in pharmaceutical formulations using 1,2-naphthoquinone-4-sulphonate.  

PubMed

New, simple and rapid spectrophotometric method has been developed and validated for the assay of two macrolide drugs, azithromycin (AZT) and erythromycin (ERY) in pure and pharmaceutical formulations. The proposed method was based on the reaction of AZT and ERY with sodium 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline medium at 25 °C to form an orange-colored product of maximum absorption peak at 452 nm. All variables were studied to optimize the reaction conditions and the reaction mechanism was postulated. Beer's law was obeyed in the concentration range 1.5-33.0 and 0.92-8.0 ?g mL(-1) with limit of detection values of 0.026 and 0.063 ?g mL(-1) for AZT and ERY, respectively. The calculated molar absorptivity values are 4.3 × 10(4) and 12.3 × 10(4) L mol(-1) cm(-1) for AZT and ERY, respectively. The proposed methods were successfully applied to the determination of AZT and ERY in formulations and the results tallied well with the label claim. The results were statistically compared with those of an official method by applying the Student's t-test and F-test. No interference was observed from the concomitant substances normally added to preparations. PMID:23041925

Ashour, Safwan; Bayram, Roula

2012-12-01

66

Novel spectrophotometric method for determination of some macrolide antibiotics in pharmaceutical formulations using 1,2-naphthoquinone-4-sulphonate  

NASA Astrophysics Data System (ADS)

New, simple and rapid spectrophotometric method has been developed and validated for the assay of two macrolide drugs, azithromycin (AZT) and erythromycin (ERY) in pure and pharmaceutical formulations. The proposed method was based on the reaction of AZT and ERY with sodium 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline medium at 25 °C to form an orange-colored product of maximum absorption peak at 452 nm. All variables were studied to optimize the reaction conditions and the reaction mechanism was postulated. Beer's law was obeyed in the concentration range 1.5-33.0 and 0.92-8.0 ?g mL-1 with limit of detection values of 0.026 and 0.063 ?g mL-1 for AZT and ERY, respectively. The calculated molar absorptivity values are 4.3 × 104 and 12.3 × 104 L mol-1 cm-1 for AZT and ERY, respectively. The proposed methods were successfully applied to the determination of AZT and ERY in formulations and the results tallied well with the label claim. The results were statistically compared with those of an official method by applying the Student's t-test and F-test. No interference was observed from the concomitant substances normally added to preparations.

Ashour, Safwan; Bayram, Roula

2012-12-01

67

Synthesis, spectral characterization, molecular structure and pharmacological studies of N'-(1, 4-naphtho-quinone-2yl) isonicotinohydrazide.  

PubMed

A simple and efficient procedure was employed for the synthesis of N'-(1,4-naphtho-quinone-2-yl) isonicotinohydrazide (NIH) by the reaction of 2-hydroxy-1,4-naphthaquinone (lawsone) and isonicotinoyl hydrazine in methanol using ultrasonic irradiation. Lawsone is the principal dye, isolated from the leaves of henna (Lawsonia inermis). Structural modification was done on the molecule aiming to get a more active derivative. The structure of the parent compound and the derivative was characterized by elemental analyses, infrared, electronic, (1)H, (13)C NMR and GC-MS spectra. The fluorescence spectral investigation of the compound was studied in DMSO and ethanol. Single crystal X-ray diffraction studies reveal that NIH crystallizes in monoclinic space group. The DNA cleavage study was monitored by gel electrophoresis method. The synthesized compound was found to have significant antioxidant activity against DPPH radical (IC50=58 ?M). The in vitro cytotoxic studies of the derivative against two human cancer cell lines MCF-7 (human breast cancer) and HCT-15 (human colon carcinoma cells) using MTT assay revealed that the compound exhibited higher cytotoxic activity with a lower IC50 value indicating its efficiency in killing the cancer cells even at low concentrations. These results suggest that the structural modifications performed on lawsone could be considered a good strategy to obtain a more active drug. PMID:25153640

Kavitha Rani, P R; Fernandez, Annette; George, Annie; Remadevi, V K; Sudarsanakumar, M R; Laila, Shiny P; Arif, Muhammed

2015-01-25

68

1,2-Naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea  

SciTech Connect

1,2-Naphthoquinone (1,2-NQ) has recently been identified as an environmental quinone in diesel exhaust particles (DEP) and atmospheric PM{sub 2.5}. We have found that this quinone is capable of causing a concentration-dependent contraction of tracheal smooth muscle in guinea pigs with EC{sub 5} value of 18.7 {mu}M. The contraction required extracellular calcium and was suppressed by L-type calcium channel blockers nifedipine and diltiazem. It was found that 1,2-NQ activated phospholipase A2 (PLA2)/lipoxygenase (LO)/vanilloid receptor (VR1) signaling. Additionally, 1,2-NQ was capable of transactivating protein tyrosine kinases (PTKs) such as epidermal growth factor receptor (EGFR) in guinea pig trachea, suggesting that phosphorylation of PTKs contributes to 1,2-NQ-induced tracheal contraction. Consistent with this notion, this action was blocked by the PTKs inhibitor genistein and the EGFR antagonist PD153035, indicating that contraction was, at least in part, attributable to PTKs phosphorylation that activates VR1, resulting in increased intracellular calcium content in the smooth muscle cells.

Kikuno, Shota [Master's Program in Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Taguchi, Keiko [Department of Environmental Medicine, Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Iwamoto, Noriko [Department of Environmental Medicine, Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Yamano, Shigeru [Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180 (Japan); Cho, Arthur K. [Southern California Particle Center and Supersite, Institute of the Environment, University of California, Los Angeles, Los Angeles, CA 90095 (United States); Froines, John R. [Southern California Particle Center and Supersite, Institute of the Environment, University of California, Los Angeles, Los Angeles, CA 90095 (United States); Kumagai, Yoshito [Department of Environmental Medicine, Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan) and Southern California Particle Center and Supersite, Institute of the Environment, University of California, Los Angeles, Los Angeles, CA 90095 (United States)]. E-mail: yk-em-tu@md.tsukuba.ac.jp

2006-01-15

69

Oxidative phenylamination of 5-substituted 1-hydroxynaphthalenes to N-phenyl-1,4-naphthoquinone monoimines by air and light "on water"  

PubMed Central

Summary A number of N-phenyl-1,4-naphthoquinone monoimines 6–10 were prepared by on-water oxidative phenylamination of 1,5-dihydroxynaphthalene (1) and 5-acetylamino-1-hydroxynaphthalene (5) with oxygen-substituted phenylamines under aerobic conditions and either solar or green LED radiation, in the presence of rose bengal as singlet oxygen sensitizer. As compared to the conventional oxidative phenylamination procedures, this novel synthetic method offers the advantage of aerobic conditions “on water” instead of hazardous oxidant reagents currently employed in aqueous alcoholic media. PMID:25383115

Melendez, Juan; Estela, Cynthia; Rios, David; Espinoza, Luis; Brito, Ivan; Valderrama, Jaime A

2014-01-01

70

Synthesis and some physiochemical properties of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone 4-imine derivatives.  

PubMed

Some derivatives of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)- 1,4-naphthoquinone 4-imine (3), a poorly soluble drug, were synthesized in an attempt to improve their physicochemical properties. The new compounds were characterized by spectroscopic methods including an iterative NMR method (the LAOCOON III program). The physicochemical properties such as solubility, relative lipophilicity (RM), and partition coefficients (Leo-Hansch fragmental system) were determined. Some derivatives were more lipophilic than 3 and one was water soluble. In vitro antibacterial activity was also reported for some derivatives. PMID:8207676

Sperandeo, N R; de Bertorello, M M; Briñón, M C

1994-03-01

71

Novel spectrophotometric method for determination of cinacalcet hydrochloride in its tablets via derivatization with 1,2-naphthoquinone-4-sulphonate.  

PubMed

This study represents the first report on the development of a novel spectrophotometric method for determination of cinacalcet hydrochloride (CIN) in its tablet dosage forms. Studies were carried out to investigate the reaction between CIN and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 8.5), an orange red-colored product exhibiting maximum absorption peak (?max) at 490 nm was produced. The stoichiometry and kinetic of the reaction were investigated and the reaction mechanism was postulated. This color-developing reaction was employed in the development of a simple and rapid visible-spectrophotometric method for determination of CIN in its tablets. Under the optimized reaction conditions, Beer's law correlating the absorbance with CIN concentration was obeyed in the range of 3 - 100 ?g/ml with good correlation coefficient (0.9993). The molar absorptivity (?) was 4.2 × 105 l/mol/cm. The limits of detection and quantification were 1.9 and 5.7 ?g/ml, respectively. The precision of the method was satisfactory; the values of relative standard deviations (RSD) did not exceed 2%. No interference was observed from the excipients that are present in the tablets. The proposed method was applied successfully for the determination of CIN in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 100.80 - 102.23 ± 1.27 - 1.62%. The results were compared favorably with those of a reference pre-validated method. The method is practical and valuable in terms of its routine application in quality control laboratories. PMID:22305461

Darwish, Ibrahim A; Al-Shehri, Mona M; El-Gendy, Manal A

2012-01-01

72

Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues  

PubMed Central

Background Naphthoquinones (NQs) are privileged structures in medicinal chemistry due to the biological effects associated with the induction of oxidative stress. The present study evaluated the activities of sixteen NQs derivatives on Trypanosoma cruzi. Results Fourteen NQs displayed higher activity against bloodstream trypomastigotes of T. cruzi than benznidazole. Further assays with NQ1, NQ8, NQ9 and NQ12 showed inhibition of the proliferation of axenic epimastigotes and intracelulluar amastigotes interiorized in macrophages and in heart muscle cells. NQ8 was the most active NQ against both proliferative forms of T. cruzi. In epimastigotes the four NQs induced mitochondrial swelling, vacuolization, and flagellar blebbing. The treatment with NQs also induced the appearance of large endoplasmic reticulum profiles surrounding different cellular structures and of myelin-like membranous contours, morphological characteristics of an autophagic process. At IC50 concentration, NQ8 totally disrupted the ??m of about 20% of the parasites, suggesting the induction of a sub-population with metabolically inactive mitochondria. On the other hand, NQ1, NQ9 or NQ12 led only to a discrete decrease of TMRE + labeling at IC50 values. NQ8 led also to an increase in the percentage of parasites labeled with DHE, indicative of ROS production, possibly the cause of the observed mitochondrial swelling. The other three NQs behaved similarly to untreated controls. Conclusions NQ1, NQ8, NQ9 and NQ12 induce an autophagic phenotype in T. cruzi epimastigoted, as already observed with others NQs. The absence of oxidative stress in NQ1-, NQ9- and NQ12-treated parasites could be due to the existence of more than one mechanism of action involved in their trypanocidal activity, leaving ROS generation suppressed by the detoxification system of the parasite. The strong redox effect of NQ8 could be associated to the presence of the acetyl group in its structure facilitating quinone reduction, as previously demonstrated by electrochemical analysis. Further experiments using biochemical and molecular approaches are needed to better characterize ROS participation in the mechanism of action of these NQs. PMID:24004461

2013-01-01

73

Anti-gastric adenocarcinoma activity of 2-Methoxy-1,4-naphthoquinone, an anti-Helicobacter pylori compound from Impatiens balsamina L.  

PubMed

2-Methoxy-1,4-naphthoquinone (MeONQ) from Impatiens balsamina L. exhibited strong anti-H. pylori activity in our previous study. In this study, we investigated the cytotoxicity of MeONQ against gastric adenocarcinoma (MKN45 cell line) and propose the relevant mechanisms. MeONQ resulted in serious necrosis via superoxide anion catastrophe when the treatment doses were higher than 50?M, whereas apoptosis occurred at low treatment doses (25-50?M) through the caspase-dependent apoptosis pathway. Necrosis is the dominant mode of cell death. MeONQ exhibited high ability to induce gastric adenocarcinoma necrosis, showing good potential as a candidate agent for H. pylori infection related disease therapy. PMID:22516543

Wang, Yuan-Chuen; Lin, Yi-Han

2012-12-01

74

Role of 2-amino-3-carboxy-1,4-naphthoquinone, a strong growth stimulator for bifidobacteria, as an electron transfer mediator for NAD(P) + regeneration in Bifidobacterium longum  

Microsoft Academic Search

2-Amino-3-carboxy-1,4-naphthoquinone (ACNQ) is a novel growth stimulator for bifidobacteria. The role of ACNQ as a mediator of the electron transfer from NAD(P)H to dioxygen (O2) and hydrogen peroxide (H2O2), proposed in our previous paper, was examined using the cell-free extract and whole cells of Bifidobacterium longum. Continuous monitoring of ACNQ, O2 and H2O2 by several amperometric techniques has revealed that

Shin-ichi Yamazaki; Kenji Kano; Tokuji Ikeda; Kakuhei Isawa; Tsutomu Kaneko

1999-01-01

75

Genotoxicity of 1,4-benzoquinone and 1,4-naphthoquinone in relation to effects on glutathione and NAD(P)H levels in V79 cells  

SciTech Connect

1,4-Benzoquinone is cytotoxic in V79 Chinese hamster cells and induces gene mutations and micronuclei. The cell-damaging effects of quinones are usually attributed to thiol depletion, oxidation of NAD(P)H, and redox-cycling involving the formation of semiquinone radicals and reactive oxygen species. To elucidate the role of these mechanisms in the genotoxicity of 1,4-benzoquinone, the authors measured various genotoxic effects, cytotoxicity, and the levels of glutathione, NADPH, NADH, and their oxidized forms all in the same experiment. 1,4-Naphthoquinone, which does not induce gene mutations in V79 cells, was investigated for comparative reasons. The quinones had a similar effect on the levels of cofactors. Total glutathione was depleted, but levels of oxidized glutathione were slightly increased. The levels of NADPH and NADH were reduced at high concentrations of the quinones with a simultaneous increase in the levels of NADP{sup +} and NAD{sup +}. Both compounds induced micronuclei, but neither increased the frequency of sister chromatid exchange. Only 1,4-benzoquinone induced gene mutations. They conclude that (a) induction of micronuclei and glutathione depletion by the two quinones are not linked casually, (b) 1,4-benzoquinone induces gene mutations by a mechanism different from oxidative stress and glutathione depletion, and (c) glutathione does not fully protect the cells against the genotoxicity of quinones.

Ludewig, G.; Dogra, S.; Glatt, H. (Univ. of Mainz (West Germany))

1989-07-01

76

Synthesis, antiprotozoal and cytotoxic activities of new N-(3,4-dimethyl-5-isoxazolyl)-1,2-naphthoquinone-4-amino derivatives.  

PubMed

Three derivatives of N-(3,4-dimethyl-5-isoxazolyl)-1,2-naphthoquinone-4-amino (1), a compound which exhibits significant activity against Trypanosoma cruzi and Plasmodium falciparum but with cytotoxicity toward murine L-6 cells, were synthesized with the aim of ameliorating its cytotoxicity. The in vitro antiprotozoal and cytotoxic activities of the synthesized compounds were evaluated against T. cruzi, Trypanosoma brucei rhodesiense, P. falciparum and murine L-6 cells. The hydroxymethyl (2) and the oxime (3) derivatives were active against T. cruzi, with IC50 values in a range comparable to those of 1 (IC50: 0.65 microg/ml) and benznidazole (IC50: 0.56 microg/ml) while the carboxymethyloxime (4) was inactive. Compounds 2 and 3 were cytotoxic toward L-6 cells, with IC50 values identical to that of 1 (IC50: 0.50 microg/ml). The results did not support the suggestion that 2 and 3 may be used as prodrugs of 1. PMID:15178304

Sperandeo, N R; Briñón, M C; Brun, R

2004-06-01

77

[Influence of 2-aryl-3-halogen/3-hydroxy-1,4-naphthoquinones with salicylic and cinnamic acid partial structures on the arachidonic acid cascade].  

PubMed

Searching for more potent 5-lipoxygenase (LO) inhibitors one tert-butyl group of the selective 5-LO-inhibitor 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-1,4-naphthoquinone (1) was substituted by polar functions (-CHO, -COOH, -CH=CH-COOR, -CH2-CH2-COOR). At the same time the 5-LO selectivity of the new compounds within the arachidonic acid cascade was investigated. For this 12-LO- and COX-1-assays with activated human platelets were used. Screening the test compounds new selective 5-LO-inhibitors (4, 9 and 16) and a COX-1-inhibitor (10) as well as dual 5-LO/COX-1- (23) and 12-LO/COX-1- (12) inhibiting compounds were found. Obviously in this class of compounds 5-LO and 12-LO inhibition are mutually excluded for a structural reason. In addition to the well known 3-chloro- (19) and 3-bromo- (20) analogues of 1 the 3-fluoro- (22), 3-iodo- (23) and the 3-carbonitrile- (24) derivatives were synthesized. All 3-halogen compounds, except 23 and the nitrile, are potent non selective inhibitors of all three enzymes. Causative for this unselectivity is the inhibition of the arachidonic acid release by inhibition of the cytosolic phospholipase A2 (cPLA2) with the exception of 24. PMID:15074584

Richwien, A; Wurm, G

2004-03-01

78

Selective Spectrophotometric and Spectrofluorometric Methods for the Determination of Amantadine Hydrochloride in Capsules and Plasma via Derivatization with 1,2-Naphthoquinone-4-sulphonate  

PubMed Central

New selective and sensitive spectrophotometric and spectrofluorometric methods have been developed and validated for the determination of amantadine hydrochloride (AMD) in capsules and plasma. The methods were based on the condensation of AMD with 1,2-naphthoquinone-4-sulphonate (NQS) in an alkaline medium to form an orange-colored product. The spectrophotometric method involved the measurement of the colored product at 460 ?nm. The spectrofluorometric method involved the reduction of the product with potassium borohydride, and the subsequent measurement of the formed fluorescent reduced AMD-NQS product at 382 ?nm after excitation at 293 ?nm. The variables that affected the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9972–0.9974) and low LOD (1.39 and 0.013??g?mL?1) were obtained in the ranges of 5–80 and 0.05–10? ?g?mL?1 for the spectrophotometric and spectrofluorometric methods, respectively. The precisions of the methods were satisfactory; RSD ?2.04%. Both methods were successfully applied to the determination of AMD in capsules. As its higher sensitivity, the spectrofluorometric method was applied to the determination of AMD in plasma; the recovery was 96.3–101.2 ± 0.57–4.2%. The results obtained by the proposed methods were comparable with those obtained by the official method PMID:20140080

Mahmoud, Ashraf M.; Khalil, Nasr Y.; Darwish, Ibrahim A.; Aboul-Fadl, Tarek

2009-01-01

79

A Novel Color Change Mechanism for Breast Cancer Biomarker Detection: Naphthoquinones as Specific Ligands of Human Arylamine N-Acetyltransferase 1  

PubMed Central

Human arylamine N-acetyltransferase 1 (hNAT1) has become an attractive potential biomarker for estrogen-receptor-positive breast cancers. We describe here the mechanism of action of a selective non-covalent colorimetric biosensor for the recognition of hNAT1 and its murine homologue, mNat2, over their respective isoenzymes, leading to new opportunities in diagnosis. On interaction with the enzyme, the naphthoquinone probe undergoes an instantaneous and striking visible color change from red to blue. Spectroscopic, chemical, molecular modelling and biochemical studies reported here show that the color change is mediated by selective recognition between the conjugate base of the sulfonamide group within the probe and the conjugate acid of the arginine residue within the active site of both hNAT1 and mNat2. This represents a new mechanism for selective biomarker sensing and may be exploited as a general approach to the specific detection of biomarkers in disease. PMID:23940600

Varney, Amy; Thinnes, Cyrille C.; Quevedo, Camilo E.; Seden, Peter T.; Thompson, Sam; Rodrigues-Lima, Fernando; Dairou, Julien; Dupret, Jean-Marie; Russell, Angela J.; Sim, Edith

2013-01-01

80

7Ethyl2,3,5,6,8-pentahydroxy-1,4-naphthoquinone (echinochrome A): A DFT study of the antioxidant mechanism. 1. Interaction of echinochrome A with hydroperoxyl radical  

Microsoft Academic Search

The molecular geometry and electronic structure of hydroxy-substituted naphthazarin (NZ)-7-ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone\\u000a (echinochrome A, (Et)NZ(?-OH)3, 1) were calculated by the B3LYP\\/6-311G(d) method. The influence of the (i) character of the ?-OH groups dissociation and (ii)\\u000a conformational mobility of molecule 1 and the anions, radicals, and radical anions derived from 1 on the energy of their reactions with hydroperoxyl radical was studied by

D. V. Berdyshev; V. P. Glazunov; V. L. Novikov

2007-01-01

81

The crystal structure and physicochemical characteristics of 2-hydroxy-N-[3(5)-pyrazolyl]-1,4-naphthoquinone-4-imine, a new antitrypanosomal compound.  

PubMed

This study was designed to investigate the physical characteristics and crystalline structure of 2-hydroxy-N-[3(5)-pyrazolyl]-1,4-naphthoquinone-4-imine (PNQ), a new active compound against Trypanosoma cruzi, the causative agent of American trypanosomiasis. Methods used included differential scanning calorimetry, thermogravimetry, hot stage microscopy, polarized light microscopy (PLM), Fourier-transform infrared (FTIR) spectroscopy, and high-resolution X-ray powder diffraction (HR-XRPD). According to PLM and HR-XRPD data, PNQ crystallized as red oolitic crystals (absolute methanol) or prisms (dimethyl sulfoxide [DMSO]-water) with the same internal structure. The findings obtained with HR-XRPD data (applying molecular location methods) showed a monoclinic unit cell [a = 18.4437(1) A, b = 3.9968(2) A, c = 14.5304(1) A, alpha = 90 degrees , beta = 102.71(6) degrees , gamma = 90 degrees , V = 1044.9(1) A(3), Z = 4, space group P2(1)/c], and a crystal structure (excluding H-positions) described by parallel layers in the direction of the b-axis, with molecules held by homochemical (phenyl-phenyl and pyrazole-pyrazole) van der Waals interactions. In addition, FTIR spectra displayed the NH-pyrazole stretch overlapped with the OH absorption at 3222 cm(-1), typical of -NH and -OH groups associated through H-bondings; and a carbonyl stretching absorption at 1694 cm(-1), indicating a nonextensively H-bonded quinonic C=O, which was in accordance with the solved crystal structure of PNQ. The existence of such cohesive forces shed light on the thermoanalytical data, which revealed that PNQ is a stable solid, unaffected by oxygen that decomposed without melting above 260 degrees C. PMID:16408868

Sperandeo, Norma R; Karlsson, Alicia; Cuffini, Silvia; Pagola, Silvina; Stephens, Peter W

2005-01-01

82

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), isolated from Plumbago zeylanica, inhibits ultraviolet radiation-induced development of squamous cell carcinomas  

PubMed Central

Plumbagin (PL) (5-hydroxy-2-methyl-1,4-napthoquinone), a medicinal plant-derived naphthoquinone, was isolated from the roots of the Plumbago zeylanica L. (also known as Chitrak). The roots of P. zeylanica L. have been used in Indian medicine for >2500 years as an anti-atherogenic, cardiotonic, hepatoprotective and neuroprotective agent. We present here that topical application of non-toxic doses (100–500 nmol) of PL to skin elicits dose-dependent inhibition of ultraviolet radiation (UVR)-induced development of squamous cell carcinomas (SCC). In this experiment, FVB/N mice were exposed to UVR (2 kJ/m2) three times weekly from a bank of six Kodacel-filtered FS40 sunlamps (?60% UVB and 40% UVA). Carcinoma incidence in mice treated with vehicle, 100, 200 or 500 nmol PL, at 44 weeks post-UVR, were 86, 80 (P = 0.67), 53 (P = 0.12) and 7% (P = 0.0075), respectively. Both vehicle and PL-treated mice gained weight and did not exhibit any signs of toxicity during the entire period of the experiment. Molecular mechanisms associated with inhibition of UVR-induced development of SCC involved induction of apoptosis and inhibition of cell proliferation. Specific findings are that PL treatment (i) inhibited UVR-induced DNA binding of activating protein-1, nuclear factor-kappaB, Stat3 transcription factors and Stat3-regulated molecules (cdc25A and Survivin); (ii) inhibited protein levels of pERK1/2, PI3K85, pAKTSer473, Bcl2, BclxL, proliferating cell nuclear antigen and cell cycle inhibitory proteins p27 and p21 and (iii) increased UVR-induced Fas-associated death domain expression, poly (ADP-ribose) polymerase protein cleavage and Bax/Bcl2 ratio. Taken together, our findings suggest that PL may be a novel agent for the prevention of skin cancer. PMID:22072620

Sand, Jordan M.; Hafeez, Bilal Bin; Jamal, Mohammad Sarwar; Witkowsky, Olya; Siebers, Emily M.; Fischer, Joseph; Verma, Ajit K.

2012-01-01

83

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), isolated from Plumbago zeylanica, inhibits ultraviolet radiation-induced development of squamous cell carcinomas.  

PubMed

Plumbagin (PL) (5-hydroxy-2-methyl-1,4-napthoquinone), a medicinal plant-derived naphthoquinone, was isolated from the roots of the Plumbago zeylanica L. (also known as Chitrak). The roots of P. zeylanica L. have been used in Indian medicine for >2500 years as an anti-atherogenic, cardiotonic, hepatoprotective and neuroprotective agent. We present here that topical application of non-toxic doses (100-500 nmol) of PL to skin elicits dose-dependent inhibition of ultraviolet radiation (UVR)-induced development of squamous cell carcinomas (SCC). In this experiment, FVB/N mice were exposed to UVR (2 kJ/m(2)) three times weekly from a bank of six Kodacel-filtered FS40 sunlamps (? 60% UVB and 40% UVA). Carcinoma incidence in mice treated with vehicle, 100, 200 or 500 nmol PL, at 44 weeks post-UVR, were 86, 80 (P = 0.67), 53 (P = 0.12) and 7% (P = 0.0075), respectively. Both vehicle and PL-treated mice gained weight and did not exhibit any signs of toxicity during the entire period of the experiment. Molecular mechanisms associated with inhibition of UVR-induced development of SCC involved induction of apoptosis and inhibition of cell proliferation. Specific findings are that PL treatment (i) inhibited UVR-induced DNA binding of activating protein-1, nuclear factor-kappaB, Stat3 transcription factors and Stat3-regulated molecules (cdc25A and Survivin); (ii) inhibited protein levels of pERK1/2, PI3K85, pAKTSer473, Bcl(2), BclxL, proliferating cell nuclear antigen and cell cycle inhibitory proteins p27 and p21 and (iii) increased UVR-induced Fas-associated death domain expression, poly (ADP-ribose) polymerase protein cleavage and Bax/Bcl(2) ratio. Taken together, our findings suggest that PL may be a novel agent for the prevention of skin cancer. PMID:22072620

Sand, Jordan M; Bin Hafeez, Bilal; Jamal, Mohammad Sarwar; Witkowsky, Olya; Siebers, Emily M; Fischer, Joseph; Verma, Ajit K

2012-01-01

84

The Antimalarial Activities of Methylene Blue and the 1,4-Naphthoquinone 3-[4-(Trifluoromethyl)Benzyl]-Menadione Are Not Due to Inhibition of the Mitochondrial Electron Transport Chain  

PubMed Central

Methylene blue and a series of recently developed 1,4-naphthoquinones, including 3-[4-(substituted)benzyl]-menadiones, are potent antimalarial agents in vitro and in vivo. The activity of these structurally diverse compounds against the human malaria parasite Plasmodium falciparum might involve their peculiar redox properties. According to the current theory, redox-active methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione are “subversive substrates.” These agents are thought to shuttle electrons from reduced flavoproteins to acceptors such as hemoglobin-associated or free Fe(III)-protoporphyrin IX. The reduction of Fe(III)-protoporphyrin IX could subsequently prevent essential hemoglobin digestion and heme detoxification in the parasite. Alternatively, owing to their structures and redox properties, methylene blue and 1,4-naphthoquinones might also affect the mitochondrial electron transport chain. Here, we tested the latter hypothesis using an established system of transgenic P. falciparum cell lines and the antimalarial agents atovaquone and chloroquine as controls. In contrast to atovaquone, methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione do not inhibit the mitochondrial electron transport chain. A systematic comparison of the morphologies of drug-treated parasites furthermore suggests that the three drugs do not share a mechanism of action. Our findings support the idea that methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione exert their antimalarial activity as redox-active subversive substrates. PMID:23439633

Ehrhardt, Katharina; Ke, Hangjun; Vaidya, Akhil B.; Lanzer, Michael

2013-01-01

85

Charge transfer interaction of 4-acetamidophenol (paracetamol) with 2,3-dichloro-1,4-naphthoquinone: A study in aqueous ethanol medium by UV-vis spectroscopic and DFT methods  

NASA Astrophysics Data System (ADS)

4-Acetamidophenol (paracetamol) is shown to form charge transfer complex with 2,3-dichloro1,4-naphthoquinone in aqueous ethanol media exhibiting the unusual 2:1 (paracetamol:quinone) stoichiometry. The complexation enthalpy and entropy have been estimated from the formation constant ( K) determined spectrophotometrically at five different temperatures. In aqueous ethanol mixtures of varying composition K increases with increasing dielectric constant of the medium. This has been rationalized by calculating the electronic charge distribution in paracetamol molecule and its conjugate base at the DFT/B3LYP/6-31++G(d,p) level. The theoretically calculated vertical ionization potential of paracetamol also agrees with reported experimental value.

Saha, Avijit; Tiwary, Amit S.; Mukherjee, Asok K.

2008-12-01

86

In Vitro Activity of 2-methoxy-1,4-naphthoquinone and Stigmasta-7,22-diene-3?-ol from Impatiens balsamina L. against Multiple Antibiotic-Resistant Helicobacter pylori  

PubMed Central

Infection with Helicobacter pylori is strongly associated with gastric cancer and gastric adenocarcinoma. WHO classified H. pylori as a group 1 carcinogen in 1994. Impatiens balsamina L. has been used as indigenous medicine in Asia for the treatment of rheumatism, fractures and fingernail inflammation. In this study, we isolated anti-H. pylori compounds from this plant and investigated their anti- and bactericidal activity. Compounds of 2-methoxy-1,4-naphthoquinone (MeONQ) and stigmasta-7,22-diene-3?-ol (spinasterol) were isolated from the pods and roots/stems/leaves of I. balsamina L., respectively. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for MeONQ were in the ranges of 0.156–0.625 and 0.313–0.625 ?g mL?1, respectively, and in the ranges of 20–80??g mL?1 both of MICs and MBCs for spinasterol against antibiotic (clarithromycin, metronidazole and levofloxacin) resistant H. pylori. Notably, the activity of MeONQ was equivalent to that of amoxicillin (AMX). The bactericidal H. pylori action of MeONQ was dose-dependent. Furthermore, the activity of MeONQ was not influenced by the environmental pH values (4–8) and demonstrated good thermal (121°C for 15 min) stability. MeONQ abounds in the I. balsamina L. pod at the level of 4.39% (w/w db). In conclusion, MeONQ exhibits strong potential to be developed as a candidate agent for the eradication of H. pylori infection. PMID:19773391

Wang, Yuan-Chuen; Li, Wan-Yu; Wu, Deng-Chyang; Wang, Jeh-Jeng; Wu, Cheng-Hsun; Liao, Jyun-Ji; Lin, Cheng-Kun

2011-01-01

87

In Vitro Activity of 2-methoxy-1,4-naphthoquinone and Stigmasta-7,22-diene-3?-ol from Impatiens balsamina L. against Multiple Antibiotic-Resistant Helicobacter pylori.  

PubMed

Infection with Helicobacter pylori is strongly associated with gastric cancer and gastric adenocarcinoma. WHO classified H. pylori as a group 1 carcinogen in 1994. Impatiens balsamina L. has been used as indigenous medicine in Asia for the treatment of rheumatism, fractures and fingernail inflammation. In this study, we isolated anti-H. pylori compounds from this plant and investigated their anti- and bactericidal activity. Compounds of 2-methoxy-1,4-naphthoquinone (MeONQ) and stigmasta-7,22-diene-3?-ol (spinasterol) were isolated from the pods and roots/stems/leaves of I. balsamina L., respectively. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for MeONQ were in the ranges of 0.156-0.625 and 0.313-0.625 ?g mL(-1), respectively, and in the ranges of 20-80??g mL(-1) both of MICs and MBCs for spinasterol against antibiotic (clarithromycin, metronidazole and levofloxacin) resistant H. pylori. Notably, the activity of MeONQ was equivalent to that of amoxicillin (AMX). The bactericidal H. pylori action of MeONQ was dose-dependent. Furthermore, the activity of MeONQ was not influenced by the environmental pH values (4-8) and demonstrated good thermal (121°C for 15 min) stability. MeONQ abounds in the I. balsamina L. pod at the level of 4.39% (w/w db). In conclusion, MeONQ exhibits strong potential to be developed as a candidate agent for the eradication of H. pylori infection. PMID:19773391

Wang, Yuan-Chuen; Li, Wan-Yu; Wu, Deng-Chyang; Wang, Jeh-Jeng; Wu, Cheng-Hsun; Liao, Jyun-Ji; Lin, Cheng-Kun

2011-01-01

88

Plumbagin, a medicinal plant (Plumbago zeylanica) - derived 1,4-naphthoquinone, inhibits growth and metastasis of human prostate cancer PC-3M-luciferase cells in an orthotopic xenograft mouse model  

PubMed Central

We present here first time that Plumbagin (PL), a medicinal plant-derived 1,4-naphthoquinone, inhibits the growth and metastasis of prostate cancer (PCa) in an orthotopic xenograft mouse model. In this study, human PCa PC-3M-luciferase cells (2X106) were injected into the prostate of athymic nude mice. Three days post cell implantation, mice were treated with PL (2 mg/kg body wt. i.p five days in a week) for 8 weeks. Growth and metastasis of PC-3M-luciferase cells was examined weekly by bioluminescence imaging of live mice. PL-treatment significantly (p=0.0008) inhibited the growth of orthotopic xenograft tumors. PCa metastasis into the liver, lungs and lymph nodes was determined by bioluminescence imaging and histopathology. Results demonstrated a significant inhibition of metastasis into liver (p=0.037), but inhibition of metastasis into the lungs (p=0.60) and liver (p=0.27) was not observed to be significant. These results were further confirmed by histopathology of these organs. Results of histopathology demonstrated a significant inhibition of metastasis into lymph nodes (p=0.034) and lungs (p=0.028), and a trend to significance in liver (p=0.075). None of the mice in the PL-treatment group showed PCa metastasis into the liver, but these mice had small metastasis foci into the lymph nodes and lungs. However, control mice had large metastatic foci into the lymph nodes, lungs, and liver. PL-caused inhibition of the growth and metastasis of PC-3M cells accompanies inhibition of the expression of: 1) PKC?, pStat3Tyr705, and pStat3Ser727, 2) Stat3 downstream target genes (survivin and BclxL), 3) proliferative markers Ki-67 and PCNA, 4) metastatic marker MMP9, MMP2, and uPA, and 5) angiogenesis markers CD31 and VEGF. Taken together, these results suggest that PL inhibits tumor growth and metastasis of human PCa PC3-M-luciferase cells, which could be used as a therapeutic agent for the prevention and treatment of human PCa. PL: Plumbagin, PCa: Prostate cancer. PMID:23273564

Hafeez, Bilal Bin; Zhong, Weixiong; Fischer, Joseph W.; Mustafa, Ala; Shi, Xudong Daniel; Meske, Louise; Hong, Hao; Cai, Weibo; Havighurst, Thomas; Kim, KyungMann; Verma, Ajit. K

2012-01-01

89

Plumbagin, a medicinal plant (Plumbago zeylanica)-derived 1,4-naphthoquinone, inhibits growth and metastasis of human prostate cancer PC-3M-luciferase cells in an orthotopic xenograft mouse model.  

PubMed

We present here first time that Plumbagin (PL), a medicinal plant-derived 1,4-naphthoquinone, inhibits the growth and metastasis of human prostate cancer (PCa) cells in an orthotopic xenograft mouse model. In this study, human PCa PC-3M-luciferase cells (2 × 10(6)) were injected into the prostate of athymic nude mice. Three days post cell implantation, mice were treated with PL (2 mg/kg body wt. i.p. five days in a week) for 8 weeks. Growth and metastasis of PC-3M-luciferase cells was examined weekly by bioluminescence imaging of live mice. PL-treatment significantly (p = 0.0008) inhibited the growth of orthotopic xenograft tumors. Results demonstrated a significant inhibition of metastasis into liver (p = 0.037), but inhibition of metastasis into the lungs (p = 0.60) and lymph nodes (p = 0.27) was not observed to be significant. These results were further confirmed by histopathology of these organs. Results of histopathology demonstrated a significant inhibition of metastasis into lymph nodes (p = 0.034) and lungs (p = 0.028), and a trend to significance in liver (p = 0.075). None of the mice in the PL-treatment group showed PCa metastasis into the liver, but these mice had small metastasis foci into the lymph nodes and lungs. However, control mice had large metastatic foci into the lymph nodes, lungs, and liver. PL-caused inhibition of the growth and metastasis of PC-3M cells accompanies inhibition of the expression of: 1) PKC?, pStat3Tyr705, and pStat3Ser727, 2) Stat3 downstream target genes (survivin and Bcl(xL)), 3) proliferative markers Ki-67 and PCNA, 4) metastatic marker MMP9, MMP2, and uPA, and 5) angiogenesis markers CD31 and VEGF. Taken together, these results suggest that PL inhibits tumor growth and metastasis of human PCa PC3-M-luciferase cells, which could be used as a therapeutic agent for the prevention and treatment of human PCa. PMID:23273564

Hafeez, Bilal Bin; Zhong, Weixiong; Fischer, Joseph W; Mustafa, Ala; Shi, Xudong; Meske, Louise; Hong, Hao; Cai, Weibo; Havighurst, Thomas; Kim, Kyungmann; Verma, Ajit K

2013-06-01

90

Pericyclic Reactions of Prenylated Naphthoquinones: Biomimetic  

E-print Network

bark of which is used to treat rheumatism and asthma in Chinese herbal medicine.4 Extracts from benefits. For example, the Chinese medicinal plant Rubia cordifolia has yielded the achiral chromene, astringents, and diuretics in Brazilian traditional medicine.5 Phytochemical investigations have yielded

Trauner, Dirk

91

Synthesis and Biological Evaluation of Naphthoquinone Analogs as a Novel Class of Proteasome Inhibitors  

PubMed Central

Screening of the NCI Diversity Set-1 identified PI-083 (NSC-45382) a proteasome inhibitor selective for cancer over normal cells. Focused libraries of novel compounds based on PI-083 chloronaphthoquinone and sulfonamide moieties were synthesized to gain a better understanding of the structure activity relationship responsible for chymotrypsin-like proteasome inhibitory activity. This led to the demonstration that the chloronaphthoquinone and the sulfonamide moieties are critical for inhibitory activity. The pyridyl group in PI-083 can be replaced with other heterocyclic groups without significant loss of activity. Molecular modeling studies were also performed to explore the detailed interactions of PI-083 and its derivatives with the ?5 and ?6 subunits of the 20S proteasome. The refined model showed an H-bond interaction between the Asp-114 and the sulfonamide moiety of the PI-083 in the ?6 subunit. PMID:20621484

Lawrence, Harshani R.; Kazi, Aslamuzzaman; Luo, Yunting; Kendig, Robert; Ge, Yiyu; Jain, Sanjula; Daniel, Kenyon; Santiago, Daniel; Guida, Wayne C.; Sebti, Said M.

2012-01-01

92

Cytotoxicity and cytoprotective activity in naphthalenediols depends on their tendency to form naphthoquinones.  

PubMed

We consider the cytotoxicity and the protection against oxidative stress for members of the naphthalenediol family and the known antioxidant epigallocatechin gallate (EGCG). Compounds include the 1,2-naphthalenediol (1,2-ND), 1,4-ND, 2,3-ND, 1,8-ND, and 1,4-dipropyl-2,3-naphthalenediol (DPND). The cell line is an adherent clone of rat pheochromocytoma (PC12-AC). Oxidative stress was induced by the peroxyl radical generator AAPH. The relative order of cytotoxicity was 1,4-ND > 1,2-ND > DPND > 2,3-ND > 1,8-ND > EGCG, with EC(50)'s of 15, 40, 160, >250, >250, >250 muM, respectively. Despite their high toxicity, both 1,4-ND and 1,2-ND showed narrow zones of protective behavior whereas DPND, 2,3-ND and 1,8-ND and especially EGCG showed an extended protective range. The total protection obtained for the combination of cells/oxidative stressor/protective compounds (PC12-AC/AAPH/naphthalenediols) was defined by an integrated measure, the cytoprotective area (CPA). We relate the observed cytotoxicity and CPA to the different electronic structures of the naphthalenediols, characterized by the first and second bond dissociation enthalpies and the pK(a)'s for parent (diol) and semiquinone. Since the 2,3- and 1,8-naphthalenediols do not form quinones, their cytotoxicity is much lower than for the compounds which do. Thus selected members of the naphthalenediol family show promise as antioxidants. PMID:16257646

Flueraru, Mihaela; Chichirau, Alexandru; Chepelev, Leonid L; Willmore, William G; Durst, Tony; Charron, Martin; Barclay, L R C; Wright, James S

2005-11-15

93

Isolation and chemopreventive evaluation of novel naphthoquinone compounds from Alkanna tinctoria  

PubMed Central

Botanically derived natural products have recently become an attractive source of new chemotherapeutic agents. To explore active anti-colorectal cancer compounds, we performed phytochemical studies on Alkanna tinctoria and isolated eight quinone compounds. Using different spectrum methods, compounds were identified as alkannin (1), acetylalkannin (2), angelylalkannin (3), 5-methoxyangenylalkannin (4), dimethylacryl alkannin (5), arnebifuranone (6), alkanfuranol (7), and alkandiol (8). Compounds 4, 7, and 8 are novel compounds. The structures of the three novel compounds were elucidated based on extensive spectroscopic evidence including high-resolution mass spectrometry and NMR spectra. The antiproliferative effects of these eight compounds on HCT-116 and SW-480 human colorectal cancer cells were determined by the MTS method. Cell cycle and apoptosis were determined using flow cytometry. Enzymatic activities of caspases were determined by colorimetric assay, and interactions of compound 4 and caspase 9 were explored by docking analysis. Among the eight compounds, alkannin (1), angelylalkannin (3), and 5-methoxyangenylalkannin (4) showed strong antiproliferative effects, while compound 4 showed the most potent effects. Compound 4 arrested cancer cells in the S and G2/M phases, and significantly induced cell apoptosis. The apoptotic effects of compound 4 were supported by caspase assay and docking analysis. The structural functional relationship assay suggested that to increase anticancer potential, future modifications on alkannin (1) should focus on the hydroxyl groups at C-5 and C-8. PMID:24025561

Tung, Nguyen Huu; Du, Guang-Jian; Yuan, Chun-Su; Shoyama, Yukihiro; Wang, Chong-Zhi

2013-01-01

94

Methylations of Tryptophan-Modified Naphthoquinone Affect Its Inhibitory Potential toward A Aggregation  

E-print Network

(A) is the hallmark of Alzheimer's disease (AD). Small molecules inhibiting A can be valuable for treating AD. INTRODUCTION Alzheimer's disease (AD), a progressive neurodegenerative disorder for which role of aromatic amino acids in the formation of amyloid fibrils through -stacking interactions.11

Caflisch, Amedeo

95

Potent and specific bactericidal effect of juglone (5-hydroxy-1,4-naphthoquinone) on the fire blight pathogen Erwinia amylovora.  

PubMed

A screening of plant quinones for inhibiting effects on the bacterial fire blight pathogen Erwinia amylovora was performed. The most active compound, juglone from walnuts, has a potent and specific bactericidal effect on E. amylovora and minimal inhibitory concentrations of only 2.5-10 ?M, with stronger effects at lower, but still physiological, pH values. In vitro tests with juglone and inoculated flowers of apple (Malus domestica) showed an efficacy of 67% in preventing infection. In two years of field tests juglone had variable degrees of efficacy ranging from 40 to 82%, seemingly due to environmental conditions. A phytotoxic reaction to juglone, which is known for its allelopathic effect on plants, was restricted to browning of petals; later fruit russeting was not observed. Juglone is a promising candidate for the development of a new environmentally friendly plant protectant to replace the antibiotic streptomycin currently used in fire blight control. PMID:23163769

Fischer, Thilo Christopher; Gosch, Christian; Mirbeth, Beate; Gselmann, Markus; Thallmair, Veronika; Stich, Karl

2012-12-12

96

Effects of two naphthoquinone compounds on wheat seedlings, germination of urediospores of Puccinia graminis tritici and the host parasite relationship  

E-print Network

metabolism of plants is altered by rust fungi. Yarwood, et al. (2)) found that bean plants infected with rust had a higher pantothenate content than healthy plants. Husain, et al. (7) worked out the pattern of pantothenate increase in wheat plants after.... ) Phytopathology 52:756. 7. Husain, M. , C. D. Hobbs and M. C. Futrell. 1964. Effects of infection of Puccinia graminis tritici on the vitamin B6, niacin and, pantothenic contents of wheat plants. Phytopathology 54:502-505. B. Lambert, E. B. and E. C. Stakman...

Rodriguez Campos, Enrique

2012-06-07

97

Allan, Hong and Stoltz Supporting Information Expedient Synthesis of 3-Hydroxyisoquinolines and 2-Hydroxy-1,4-naphthoquinones  

E-print Network

and back-filled with argon. Tetrahydrofuran (7.5 mL) was added and the suspension was heated to 65 �C for 3, 1.0 equiv) and tetrahydrofuran (5 mL). To this solution was added carbonyl diimidazole (0.957 g, 5

Stoltz, Brian M.

98

A new naphthoquinone isolated from the bulbs of Cipura paludosa and pharmacological activity of two main constituents.  

PubMed

Cipura paludosa (Iridaceae) is a plant that is distributed in the north region of Brazil. Its bulbs are used in folk medicine to treat inflammation and pain. Four naphthalene derivatives have been isolated from the bulbs of this plant. Three of them have been identified as the known naphthalene derivatives, eleutherine, iso-eleutherine, and hongkonin. The structure of the fourth and new component was determined as 11-hydroxyeleutherine by extensive NMR study. In addition, the IN VIVO effect of the two major compounds, eleutherine and iso-eleutherine, was evaluated in carrageenan-induced hypernociception and inflammation in mice. Eleutherine and iso-eleutherine (1.04-34.92 µmol/kg), dosed intraperitoneally (i.p.) or orally (p.o.), decreased the carrageenan-induced paw oedema (i.p. - inhibitions of 36 ± 7 % and 58 ± 14 %, respectively; p.o. - inhibitions of 36 ± 7 % and 58 ± 14 %, respectively). Iso-eleutherine, but not eleutherine, significantly reduced (inhibitions of 39 ± 4 %) the plasma extravasation induced by intradermal (i.d.) injection of carrageenan. Likewise, eleutherine and iso-eleutherine (1.04-34.92 µmol/kg, i.p. or p.o.) were also effective in preventing the carrageenan-induced hypernociceptive response (i.p. - inhibition of 59 ± 4 % and 63 ± 1 %, respectively; p.o. - inhibitions of 36 ± 7 % and 58 ± 14 %, respectively). It was also suggested that the anti-inflammatory and anti-hypernociceptive effects of eleutherine or iso-eleutherine partly depend on the interference with the synthesis or activity of mast cell products, kinins, cytokine, chemokines, prostanoids, or sympathetic amines. Our findings show that two major compounds of C. paludosa contain pharmacologically active constituents that possess antinociceptive and anti-inflammatory activity, justifying, at least in part, its popular therapeutic use for treating conditions associated with pain. PMID:21283955

Tessele, Priscila Batista; Delle Monache, Franco; Quintão, Nara Lins Meira; da Silva, Gislaine Francieli; Rocha, Lilian Wunsch; Lucena, Greice M R S; Ferreira, Vania M M; Prediger, Rui D S; Cechinel Filho, Valdir

2011-07-01

99

Vasorelaxation induced by a new naphthoquinone-oxime is mediated by NO-sGC-cGMP pathway.  

PubMed

It has been established that oximes cause endothelium-independent relaxation in blood vessels. In the present study, the cardiovascular effects of the new oxime 3-hydroxy-4-(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one (Oxime S1) derived from lapachol were evaluated. In normotensive rats, administration of Oxime S1 (10, 15, 20 and 30 mg/Kg, i.v.) produced dose-dependent reduction in blood pressure. In isolated aorta and superior mesenteric artery rings, Oxime S1 induced endothelium-independent and concentration-dependent relaxations (10(-8) M to 10(-4) M). In addition, Oxime S1-induced vasorelaxations were attenuated by hydroxocobalamin or methylene blue in aorta and by PTIO or ODQ in mesenteric artery rings, suggesting a role for the nitric oxide (NO) pathway. Additionally, Oxime S1 (30 and 100 µM) significantly increased NO concentrations (13.9 ± 1.6 nM and 17.9 ± 4.1 nM, respectively) measured by nitric oxide microsensors. Furthermore, pre-contraction with KCl (80 mM) prevented Oxime S1-derived vasorelaxation in endothelium-denuded aortic rings. Of note, combined treatment with potassium channel inhibitors also reduced Oxime S1-mediated vasorelaxation suggesting a role for potassium channels, more precisely Kir, Kv and KATP channels. We observed the involvement of BKCa channels in Oxime S1-induced relaxation in mesenteric artery rings. In conclusion, these data suggest that the Oxime S1 induces hypotension and vasorelaxation via NO pathway by activating soluble guanylate cyclase (sGC) and K+ channels. PMID:25006785

Dantas, Bruna P V; Ribeiro, Thaís P; Assis, Valéria L; Furtado, Fabíola F; Assis, Kívia S; Alves, Jeziane S; Silva, Tania M S; Camara, Celso A; França-Silva, Maria S; Veras, Robson C; Medeiros, Isac A; Alencar, Jacicarlos L; Braga, Valdir A

2014-01-01

100

Spectophotometric methods for determination of cefdinir in pharmaceutical formulations via derivatization with 1,2-naphthoquinone-4-sulfonate and 4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole.  

PubMed

Two new simple, sensitive, accurate, and precise spectrophotometric methods have been developed and validated for the determination of cefdinir (CFD) in bulk drug and in its pharmaceutical formulations. The first method was based on the reaction of CFD with 1, 2- napthaquinone-4- sulfonic acid sodium (NQS) in an alkaline medium (pH 11) to form an orange-coloured product that was measured at 490 nm. The second method depends on hydrolysis of CFD using 0.5 M NaOH at 100 °C and subsequent reaction of the formed sulfide ions with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) to form a yellow-coloured chromogen measured at 390 nm. Different variables affecting the reactions of CFD with both NQS and NBD-Cl (e.g. NaOH concentration, hydrolysis time, NQS or NBD-Cl concentration and diluting solvent) were studied and optimized. Under optimum conditions, good linear relationships with good correlation coefficients (0.9990-0.9999) were found in the range of 10-80 and 5.0-30 µg ml(-1) for NQS and NBD-Cl, respectively. The limits of assay detection and quantitation ranged from 1.097 and 0.280 and 3.656 and 0.934 µg ml(-1) for NQS and NBD-Cl, respectively. The accuracy and precision of the proposed methods were satisfactory. The proposed method is simple, rapid, precise and convenient and was successfully applied for analysis of CFD in its pharmaceutical formulations and the recovery percentages ranged from 99.25 to 100.20%. PMID:21538942

Gouda, Ayman A; Hashem, Hisham; Hassan, Wafaa

2012-12-01

101

DISCRIMINATING REDOX CYCLING AND ARYLATION PATHWAYS OF REACTIVE CHEMICAL TOXICITY IN TROUT HEPATOCYTES  

EPA Science Inventory

The toxicity of four quinones, 2,3-dimethoxy-1,4-naphthoquinone (DMONQ), 2-methyl-1,4-naphthoquinone (MNQ), 1,4-naphthoquinone (NQ), and 1,4-benzoquinone (BQ), which redox cycle or arlyate in mammalian cells, was determined in isolated trout (Oncorhynchus mykiss) hepatocytes. Mor...

102

Reactions of peroxynitrite with N,N-dimethyl- p-toluidine and 1,4-naphthoquinone. Evidence for heterolytic cleavage of a nitrogen?oxygen bond in peroxynitrous acid  

Microsoft Academic Search

Peroxynitrite (ONOO?) has been found to react with the title amine 1 and quinone 5 to form N-nitrosoamine 2 and 2,3-epoxide 6, respectively, in accord with the in situ generation of the nitrosonium and hydroperoxide ions as the respective reactive species.

Nobuaki Nonoyama; Kaori Hisatome; Chizuru Shoda; Hitomi Suzuki

1999-01-01

103

Spectrophotometric and spectrofluorimetric studies on the selective sensing of fluoride ions by Co(II) and Ni(II) complexes of naphthoquinone derivative possessing enhanced H-bonding property  

NASA Astrophysics Data System (ADS)

A novel colorimetric chemosensor based on aminonaphthoquinone (L) bearing an N-H receptor unit directly attached to quinone signaling unit has been designed, synthesized and demonstrated. The ligand showed a highly selective colorimetric response to fluoride ions based on H-bond formation with the receptor unit. The binding constants of the L and its square planar [Co(L)Cl2]·3H2O and [Ni(L)Cl2]·4H2O complexes, computed using fluorescent enhancement data, were found to be 0.6, 1.5 and 0.9 × 108 M-1, respectively, indicating enhancement of H-bond donor ability of the receptor unit, as a result of complexation with metal ions, towards fluoride ion sensing. Also, these sensors had high selectivity for fluoride ion detection over other common anions, such as Cl-, Br-, I-, AcO-, NO3-, H2PO4- and CN- in acetonitrile.

Madhupriya, Selvaraj; Elango, Kuppanagounder P.

2012-11-01

104

Studies toward the synthesis of the epoxykinamycin FL-120B': discovery of a decarbonylative photocyclization.  

PubMed

Photo-Friedel-Crafts acylation of a naphthoquinone was attempted in an effort to access a diazobenzofluorenone en route to the epoxykinamycin natural product FL-120B'. Photoirradiation of the naphthoquinone substrate which resulted in the unexpected formation of a tetracyclic naphthofuran via a decarbonylative photocyclization process is described. PMID:22571279

Scully, Stephen S; Porco, John A

2012-05-18

105

Studies Toward the Synthesis of the Epoxykinamycin FL-120B': Discovery of a Decarbonylative Photocyclization  

PubMed Central

Photo-Friedel-Crafts acylation of a naphthoquinone was attempted in an effort to access a diazobenzofluorenone en route to the epoxykinamycin natural product FL-120B'. Photoirradiation of the naphthoquinone substrate which resulted in the unexpected formation of a tetracyclic naphthofuran via a decarbonylative photocyclization process is described. PMID:22571279

Scully, Stephen S.; Porco, John A.

2012-01-01

106

Molecular Modeling of the Compounds with Nonlinear Optical Properties  

NASA Technical Reports Server (NTRS)

The molecular polarizability characteristics for a large series of naphthoquinone and quinoline derivatives have been calculated. The dependence of calculated hyperpolarizability on the positions and the number of donor and acceptor substituents is discussed.

Timofeeva, Tatiana V.; Cardelino, Beatriz H.; Clark, Ronald D.

1998-01-01

107

Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection  

Microsoft Academic Search

We describe a method for the determination of the two major urinary metabolites of vitamin K as the methyl esters of their aglycone structures, 2-methyl-3-(3 ? -3 ? -carboxy- methylpropyl)-1,4-naphthoquinone (5C-aglycone) and 2-methyl- 3-(5 ? -carboxy-3 ? -methyl-2 ? -pentenyl)-1,4-naphthoquinone (7C- aglycone), by HPLC with electrochemical detection (ECD) in the redox mode. Urinary salts were removed by reversed- phase (C

Dominic J. Harrington; Robin Soper; Christine Edwards; Geoffrey F. Savidge; Stephen J. Hodges; Martin J. Shearer

2005-01-01

108

Evidence of Quinone Metabolites of Naphthalene Covalently Bound to Sulfur Nucleophiles of Proteins of  

E-print Network

sulfhydryl groups of cysteine residues of proteins react with both naphthalene oxide (epoxide) by SN2 and SN1 reactions and quinone metabolites of naph- thalene (1,4- and 1,2-naphthoquinone) by 1,4-addition (Michael reaction), respectively. To understand the mechanism of naphthalene-induced cytotoxicity, it is important

Hammock, Bruce D.

109

Proceedings of the Seventh Walnut Council Research Symposium 17GTR-NRS-P-115 INHIBITION OF OPHIOGNOMONIA CLAVIGIGNENTI-  

E-print Network

with the fungus through wounds and their response to natural infection in the field. Butternut is known to produce naphthoquinone compounds with antimicrobial activity. These compounds, if produced at different concentrations phenolic production of black walnut confers disease resistance to that species (Nair 1999). The capability

110

Cytotoxic and Antimicrobial Constituents of the Bark of Diospyros maritima Collected in Two Geographical Locations in Indonesia  

E-print Network

Cytotoxic and Antimicrobial Constituents of the Bark of Diospyros maritima Collected in Two, Natural Products Laboratory, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, North a new naphthoquinone derivative, (4S)-shinanolone (5), and a new natural product coumarin, 7,8-dimethoxy

Falkinham, Joseph

111

Antioxidant activities of alkannin, shikonin and Alkanna tinctoria root extracts in oil substrates  

Microsoft Academic Search

Alkannin and shikonin (A\\/S) are potent pharmaceutical substances with a wide spectrum of biological properties and comprise the active ingredients of several pharmaceutical and cosmetic preparations, and are used as food colorants. From a structural point of view, A\\/S bear both the quinone (naphthoquinone) and the phenolic moiety. Several hydroquinone compounds have been studied for their antioxidant effects, but very

A. N. Assimopoulou; D. Boskou; V. P. Papageorgiou

2004-01-01

112

Quantum-chemical calculations and electron diffraction study of the equilibrium molecular structure of vitamin K3  

NASA Astrophysics Data System (ADS)

The equilibrium molecular structure of 2-methyl-1,4-naphthoquinone (vitamin K3) having C s symmetry is experimentally characterized for the first time by means of gas-phase electron diffraction using quantum-chemical calculations and data on the vibrational spectra of related compounds.

Khaikin, L. S.; Tikhonov, D. S.; Grikina, O. E.; Rykov, A. N.; Stepanov, N. F.

2014-05-01

113

Antiviral agents 3. Discovery of a novel small molecule non-nucleoside inhibitor of Hepatitis B Virus (HBV)  

Microsoft Academic Search

The discovery of a small molecule non-nucleoside inhibitor of Hepatitis B Virus is described. During our work on conocurvone derived naphthoquinone ‘trimers’ for the treatment of HIV, we discovered a potent inhibitor 9 of Hepatitis B Virus in an antiviral screen. During attempts to resynthesis 9 for proof of concept studies, we altered the synthesis in order to attempt to

Ian T. Crosby; David G. Bourke; Eric D. Jones; Tyrone P. Jeynes; Susan Cox; Jonathan A. V. Coates; Alan D. Robertson

2011-01-01

114

Antipruritic dinaphthofuran-7,12-dione derivatives from the pericarp of Impatiens balsamina.  

PubMed

Dinaphthofuran-7,12-dione derivatives named balsaminones A (1) and B (2) were isolated from the pericarp of Impatiens balsamina L. together with the known compound 2-methoxy-1,4-naphthoquinone (3). Their structures were elucidated by spectral techniques. These compounds have significant antipruritic activity. PMID:9748380

Ishiguro, K; Ohira, Y; Oku, H

1998-09-01

115

Expression of Pigment Cell-Specific Genes in the Ontogenesis of the Sea Urchin Strongylocentrotus intermedius  

PubMed Central

One of the polyketide compounds, the naphthoquinone pigment echinochrome, is synthesized in sea urchin pigment cells. We analyzed polyketide synthase (pks) and sulfotransferase (sult) gene expression in embryos and larvae of the sea urchin Strongylocentrotus intermedius from various stages of development and in specific tissues of the adults. We observed the highest level of expression of the pks and sult genes at the gastrula stage. In unfertilized eggs, only trace amounts of the pks and sult transcripts were detected, whereas no transcripts of these genes were observed in spermatozoids. The addition of shikimic acid, a precursor of naphthoquinone pigments, to zygotes and embryos increased the expression of the pks and sult genes. Our findings, including the development of specific conditions to promote pigment cell differentiation of embryonic sea urchin cells in culture, represent a definitive study on the molecular signaling pathways that are involved in the biosynthesis of pigments during sea urchin development. PMID:21804858

Ageenko, Natalya V.; Kiselev, Konstantin V.; Odintsova, Nelly A.

2011-01-01

116

Expression of Pigment Cell-Specific Genes in the Ontogenesis of the Sea Urchin Strongylocentrotus intermedius.  

PubMed

One of the polyketide compounds, the naphthoquinone pigment echinochrome, is synthesized in sea urchin pigment cells. We analyzed polyketide synthase (pks) and sulfotransferase (sult) gene expression in embryos and larvae of the sea urchin Strongylocentrotus intermedius from various stages of development and in specific tissues of the adults. We observed the highest level of expression of the pks and sult genes at the gastrula stage. In unfertilized eggs, only trace amounts of the pks and sult transcripts were detected, whereas no transcripts of these genes were observed in spermatozoids. The addition of shikimic acid, a precursor of naphthoquinone pigments, to zygotes and embryos increased the expression of the pks and sult genes. Our findings, including the development of specific conditions to promote pigment cell differentiation of embryonic sea urchin cells in culture, represent a definitive study on the molecular signaling pathways that are involved in the biosynthesis of pigments during sea urchin development. PMID:21804858

Ageenko, Natalya V; Kiselev, Konstantin V; Odintsova, Nelly A

2011-01-01

117

Antibacterial activity of some natural products against bacteria expressing a multidrug-resistant phenotype  

Microsoft Academic Search

The present study assessed the antimicrobial activities of various natural products belonging to the terpenoids, alkaloids and phenolics against a collection of Gram-negative multidrug-resistant (MDR) bacteria. The results demonstrated that most of the compounds were extruded by bacterial efflux pumps. In the presence of the efflux pump inhibitor phenylalanine arginine ?-naphthylamide (PA?N), the activities of laurentixanthone B (xanthone), plumbagin (naphthoquinone),

V. Kuete; S. Alibert-Franco; K. O. Eyong; B. Ngameni; G. N. Folefoc; J. R. Nguemeving; J. G. Tangmouo; G. W. Fotso; J. Komguem; B. M. W. Ouahouo; J.-M. Bolla; J. Chevalier; B. T. Ngadjui; A. E. Nkengfack; J.-M. Pagès

2011-01-01

118

Extraction of Bioactive Compounds From Leaves of lawsonia Inermis by Green Pressurized Fluids  

Microsoft Academic Search

Supercritical carbon dioxide and microwave-assisted hydrothermal methods were investigated for extraction of bioactive components of leaves of Lawsonia inermis (henna), a world renowned source of natural hair dye component called lawsone (2-hydroxy-1,4-naphthoquinone). Results showed that the use of supercritical carbon dioxide was selective to extraction of non-polar compounds such as essential oils, and recovery of lawsone was low. However, using

Tayyebeh Haleh Zohourian; Armando T. Quitain; Mitsuru Sasaki; Motonobu Goto

2012-01-01

119

Plumbagin inhibits cell growth and potentiates apoptosis in human gastric cancer cells in vitro through the NF-?B signaling pathway  

Microsoft Academic Search

Aim:To investigate the effects and underlying mechanisms of plumbagin, a naphthoquinone derived from medicinal plant Plumbago zeylanica, on human gastric cancer (GC) cells.Methods:Human gastric cancer cell lines SGC-7901, MKN-28, and AGS were used. The cell viability was examined using CCK-8 viability assay. Cell proliferation rate was determined using both clonogenic assay and EdU incorporation assay. Apoptosis was detected via Annexin

Jing Li; Lin Shen; Fu-rong Lu; You Qin; Rui Chen; Jia Li; Yan Li; Han-zi Zhan; Yuan-qiao He

2012-01-01

120

Ultrasound-mediated release of iron from ferritin  

Microsoft Academic Search

We investigated the release of iron from ferritin in aqueous solutions exposed to high-frequency ultrasound (US). Our data suggests that superoxide produced as a result of ultrasonic cavitation acts as a reducing agent, enabling the release of iron from ferritin. We also found that the release of ferritin iron during US exposure is enhanced by the addition of 5-hydroxy-1,4-naphthoquinone. We

Jody M. Morrissey; Kevin D. Taylor; S. Douglass Gilman

2003-01-01

121

Regioselective synthesis of 6-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-7,8-diones as potent antitumoral agents.  

PubMed

Three-component coupling of aldehyde, 2-hydroxy-1,4-naphthoquinone and 3-amino-1,2,4-triazole has been achieved using a catalytic amount of sulfamic acid under solvent free conditions to produce a novel series of 6-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-7,8-dione derivatives in good yields and with high regioselectivity. These compounds are found to exhibit potent antitumoral properties. PMID:23871222

Wu, Liqiang; Zhang, Chong; Li, Weilin

2013-09-01

122

Synthesis of new calix[4]pyrrole derivatives via 1,3-dipolar cycloadditions  

Microsoft Academic Search

Octamethylcalix[4]pyrrole-2-carbaldehyde 1 and 3-(octamethylcalix[4]pyrrol-2-yl)propenal 5 were used as precursors of azomethine ylides, which were trapped in situ with a range of dipolarophiles, such as 1,4-benzoquinone, 1,4-naphthoquinone, and fumaronitrile. Aldehyde 1 showed very low reactivity but the azomethine ylide generated from the reaction of aldehyde 5 with N-methylglycine could be trapped with those dipolarophiles to afford new ?-substituted octamethylcalix[4]pyrrole derivatives in

Andreia S. F. Farinha; Augusto C. Tomé; José A. S. Cavaleiro

2010-01-01

123

Chlorochimaphilin: a new antibiotic from Moneses uniflora.  

PubMed

A study of the antimicrobial compounds from Moneses uniflora resulted in the isolation of a novel compound, 8-chloro-2,7-dimethyl-1,4-naphthoquinone (8-chlorochimaphilin) (1), together with chimaphilin (2) and 3-hydroxychimaphilin (3) as the antimicrobial components. 2,7-Dimethyl-1,3-dihydroxynaphthyl 4-O-alpha-L-rhamnopyranoside (4) and 2,7-dimethoxy-1,4,8-trihydroxynaphthalene (6) were also isolated and identified. PMID:8984155

Saxena, G; Farmer, S W; Hancock, R E; Towers, G H

1996-01-01

124

Characterization of the redox components of transplasma membrane electron transport system from Leishmania donovani promastigotes  

Microsoft Academic Search

An investigation has been made of the points of coupling of four nonpermeable electron acceptors e.g., ?-lipoic acid (ALA), 5,5?-dithiobis (2-nitroaniline-N-sulphonic acid) (DTNS), 1,2-naphthoquinone-4-sulphonic acid (NQSA) and ferricyanide which are mainly reduced via an interaction with the redox sites present in the plasma membrane of Leishmania donovani promastigotes. ALA, DTNS, NQSA and ferricyanide reduction and part of O2 reduction is

Tanmoy Bera; Kuruba Lakshman; Debiprasad Ghanteswari; Sabita Pal; Dharmalingam Sudhahar; Nihar Ranjan Bhuyan; Pradeep Das

2005-01-01

125

Inhibition of hind-paw edema and cutaneous vascular plasma extravasation in mice by acetylshikonin  

Microsoft Academic Search

Acetylshikonin, a naphthoquinone isolated from the Chinese herb medicine, tzu ts'ao, was demonstrated to inhibit the polymyxin B-induced hind-paw edema in normal as well as in adrenalectomized mice. Liver glycogen content was increased in adrenalectomized mice pretreated with dexamethasone, but not with acetylshikonin. Like diphenhydramine, methysergide and isoproterenol, acetylshikonin reduced the plasma exudation evoked in dorsal hind-paw skin by antidromic

Jih-Pyang Wang; Shue-Ling Raung; Ling-Chu Chang; Sheng-Chu Kuo

1995-01-01

126

Cytotoxicity of menadione and related quinones in freshly isolated rat hepatocytes: effects on thiol homeostasis and energy charge.  

PubMed

The cytotoxic events in freshly isolated rat hepatocytes following exposure over 2 h to menadione (2-methyl-1,4-naphthoquinone) and two closely related quinones, 2,3-dimethyl-1,4-naphthoquinone (DMNQ) and 1,4-naphthoquinone (NQ), were examined. These quinones differ in their arylation capacity (NQ > menadione > DMNQ) and in their potential to induce redox cycling (NQ approximately menadione > DMNQ) The glutathione status (reduced and oxidized glutathione) of the hepatocytes was determined using HPLC after derivatization with monobromobimane. Protein thiols were measured spectrophotometrically and the energy charge of the cells was determined with HPLC using ion pair chromatography. The leakage of lactate dehydrogenase was used as a marker for cell viability. All three quinones caused alterations of the glutathione status of the exposed cells but the effects were markedly different. Exposure to DMNQ resulted in a slow decrease of reduced glutathione and an increase of mixed disulfides. The other two quinones caused an almost complete depletion of reduced glutathione within 5 min. Hepatocytes exposed to NQ accumulated oxidized glutathione whereas menadione-exposed hepatocytes showed increased levels of mixed disulfides. We did not find any effects of DMNQ (200 microM) on protein thiols, energy charge or cell viability. There was a clear difference in the effects of menadione and NQ on protein thiols, energy charge and cell viability; exposure to NQ resulted in a more extensive decrease of protein thiols and energy charge and an earlier onset of lactate dehydrogenase leakage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8135657

Toxopeus, C; van Holsteijn, I; Thuring, J W; Blaauboer, B J; Noordhoek, J

1993-01-01

127

Selected phytotoxins and organic extracts from endophytic fungus Edenia gomezpompae as light reaction of photosynthesis inhibitors.  

PubMed

In a search for natural herbicides, we investigated the action mechanism of the naphthoquinone spiroketals, isolated from the endophytic fungus Edenia gomezpompae: preussomerins EG1 (1) and EG4 (2), and palmarumycins CP17 (3), and CP2 (4) on the photosynthesis light reactions. The naphthoquinone spiroketals 1-4 inhibited the ATP synthesis in freshly lysed spinach thylakoids from water to MV, and they also inhibited the non-cyclic electron transport in the basal, phosphorylating and uncoupled conditions from water to MV. Therefore, they act as Hill reaction inhibitors. The results suggested that naphthoquinone spiroketals 1-4 have two interactions and inhibition site on the PSII electron transport chain. The first one involves the water splitting enzyme inhibition; and, the second on the acceptor site of PSII in a similar way that herbicide Diuron, studied by polaroghaphy and corroborated by fluorescence of the chlorophyll a of PSII. The culture medium and mycelium organic extracts from four morphological variants of E. gomezpompae were phytotoxic, and the culture medium extracts were more potent than mycelium extracts. They also act as Hill reaction inhibitors. PMID:24911268

Macías-Rubalcava, Martha Lydia; Ruiz-Velasco Sobrino, María Emma; Meléndez-González, Claudio; King-Díaz, Beatriz; Lotina-Hennsen, Blas

2014-09-01

128

Effects of ethanol on the hematotoxicity of twelve pharmaceutical and environmental agents  

SciTech Connect

The ability of ethanol (5%) to potentiate the oxidant stressor effects of twelve well-know hematoxic agents was investigated in vitro using human erythrocytes. Human whole blood was incubated with one of the following agents with and without ethanol for one hour at 37/sup 0/C: o-aminophenol (0.5 mM); p-benzoquinone (4.0 mM); butyl nitrite (1.0 mM); p-hydroxyacetophenone (3.0 mM); hydroxylamine (0.5 mM); O,N-dimethylhydroxylamine (7.0 mM); 1,2-naphthoquinone (0.4 mM); 1,4-naphthoquinone (0.5 mM); p-phenylenediamine (5.0 mM); phenylhydrazine (1.0 mM); potassium nitrite (1.0 mM) and primaquine (8.0 mM). Methemoglobin (METHB) and reduced glutathione (GSH) levels were subsequently measured. Synergistic increases in METHB levels occurred for primaquine, 1,2-naphthoquinone and p-phenylenediamine incubated with ethanol.

Calabrese, E.J.; Tilli, F.; Horton, H.M.; Stoddard, A.

1988-01-01

129

Effects of the compounds 2-methoxynaphthoquinone, 2-propoxynaphthoquinone, and 2-isopropoxynaphthoquinone on ecdysone 20-monooxygenase activity.  

PubMed

The effects of the natural compound 2-methoxy-1,4-naphthoquinone, isolated from the leaves of Impatiens glandulifera and the synthetic compounds 2-propoxy-1,4-naphthoquinone and 2-isopropoxy-1,4-naphthoquinone on ecdysone 20-monooxygenase (E-20-M) activity were examined in three insect species. Homogenates of wandering stage third instar larvae of Drosophila melanogaster, or abdomens from adult female Aedes aegypti, or fat body or midgut from fifth instar larvae of Manduca sexta were incubated with radiolabelled ecdysone and increasing concentrations (from 1 x 10(-8) to 1 x 10(-3) M) of the three compounds. All three compounds were found to inhibit in a dose-dependent fashion the E-20-M activity in the three insect species. The concentration of these compounds required to elicit a 50% inhibition of this steroid hydroxylase activity in the three insect species examined ranged from approximately 3 x 10(-5) to 7 x 10(-4) M. PMID:17694563

Mitchell, Martin J; Brescia, Aaron I; Smith, Stan L; Morgan, E David

2007-09-01

130

Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies  

PubMed Central

Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study. PMID:25099332

de Souza, Nicolli Bellotti; de Andrade, Isabel M; Carneiro, Paula F; Jardim, Guilherme AM; de Melo, Isadora MM; da Silva, Eufranio N; Krettli, Antoniana Ursine

2014-01-01

131

Sepiapterin Reductase Mediates Chemical Redox Cycling in Lung Epithelial Cells*  

PubMed Central

In the lung, chemical redox cycling generates highly toxic reactive oxygen species that can cause alveolar inflammation and damage to the epithelium, as well as fibrosis. In this study, we identified a cytosolic NADPH-dependent redox cycling activity in mouse lung epithelial cells as sepiapterin reductase (SPR), an enzyme important for the biosynthesis of tetrahydrobiopterin. Human SPR was cloned and characterized. In addition to reducing sepiapterin, SPR mediated chemical redox cycling of bipyridinium herbicides and various quinones; this activity was greatest for 1,2-naphthoquinone followed by 9,10-phenanthrenequinone, 1,4-naphthoquinone, menadione, and 2,3-dimethyl-1,4-naphthoquinone. Whereas redox cycling chemicals inhibited sepiapterin reduction, sepiapterin had no effect on redox cycling. Additionally, inhibitors such as dicoumarol, N-acetylserotonin, and indomethacin blocked sepiapterin reduction, with no effect on redox cycling. Non-redox cycling quinones, including benzoquinone and phenylquinone, were competitive inhibitors of sepiapterin reduction but noncompetitive redox cycling inhibitors. Site-directed mutagenesis of the SPR C-terminal substrate-binding site (D257H) completely inhibited sepiapterin reduction but had minimal effects on redox cycling. These data indicate that SPR-mediated reduction of sepiapterin and redox cycling occur by distinct mechanisms. The identification of SPR as a key enzyme mediating chemical redox cycling suggests that it may be important in generating cytotoxic reactive oxygen species in the lung. This activity, together with inhibition of sepiapterin reduction by redox-active chemicals and consequent deficiencies in tetrahydrobiopterin, may contribute to tissue injury. PMID:23640889

Yang, Shaojun; Jan, Yi-Hua; Gray, Joshua P.; Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

2013-01-01

132

Role of quinones on the ascorbate reduction rates of S-nitrosogluthathione  

PubMed Central

Quinones are one of the largest class of antitumor agents approved for clinical use and several antitumor quinones are in different stages of clinical and preclinical development. Many of these are metabolites of, or are, environmental toxins. Due to their chemical structure these are known to enhance electron transfer processes such as ascorbate oxidation and NO reduction. The paraquinones 2,6-dimethyl-1,4-benzoquinone (DMBQ), 1,4-benzoquinone (BQ), methyl-1,4-benzoquinone (MBQ), 2,6-dimethoxy-1,4-benzoquinone (DMOBQ), 2-hydroxymethyl-6-methoxy-1,4-benzoquinone (HMOBQ), trimethyl-1,4-benzoquinone (TMQ), tetramethyl-1,4-benzoquinone (DQ), 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UBQ-0), the paranaphthoquinones 1,4-naphthoquinone (NQ), menadione (MNQ), 1,4-naphthoquinone-2-sulfonate (NQ2S), juglone (JQ) and phenanthroquinone (PHQ) all enhance the anaerobic rate of ascorbate reduction of GSNO to produce NO and GSH. Rates of this reaction were much larger for p-benzoquinones and PHQ than for p-naphthoquinone derivatives with similar one-electron redox potentials. The quinone DMBQ also enhances the rate of NO production from S-nitrosylated bovine serum albumin (BSA-NO) upon ascorbate reduction. Density functional theory calculations suggest that stronger interactions between p-benzo- or phenanthrasemiquinones than those of p-naphthosemiquinones with GSNO are the major causes of these differences. Thus, quinones, and especially p-quinones and PHQ, could act as NO release enhancers from GSNO in biomedical systems in the presence of ascorbate. Since quinones are exogenous toxins which could enter the human body via a chemotherapeutic application or as an environmental contaminant, these could boost the release of NO from S-nitrosothiol storages in the body in the presence of ascorbate and thus enhance the responses elicited by a sudden increase in NO levels. PMID:20691779

Sanchez-Cruz, Pedro; Garcia, Carmelo; Alegria, Antonio E.

2010-01-01

133

Measurement of Protein Tyrosine Phosphatase Activity in Single Cells by Capillary Electrophoresis  

PubMed Central

A fluorescent peptide substrate was used to measure dephosphorylation by protein tyrosine phosphatases (PTP) in cell lysates, and single cells and to investigate the effect of environmental toxins on PTP activity in these systems. Dephosphorylation of the substrate by PTPN1 and PTPN2 obeyed Michaelis-Menten kinetics, with KM values of 770 ± 250 nM and 290 ± 54 nM, respectively. Dose-response curves and IC50 values were determined for the inhibition of these two enzymes by the environmental toxins Zn2+ and 1,2-naphthoquinone, as well as pervanadate. In A431 cell lysates, the reporter was a poor substrate for peptidases (degradation rate of 100 ± 8.2 fmol min?1 mg?1) but an excellent substrate for phosphatases (dephosphorylation rate of 1.4 ± 0.3 nmol min?1 mg?1). Zn2+, 1,2-naphthoquinone and pervanadate inhibited dephosphorylation of the reporter in cell lysates with IC50 values of 470 nM, 35 ?M, and 100 nM, respectively. Dephosphorylation of the reporter following loading into living single cells occurred at rates of at least 2 pmol min?1 mg?1. When single cells were exposed to 1,2-naphthoquinone (50 ?M), Zn2+ (100 ?M), and pervandate (1 mM), dephosphorylation was inhibited with median values and first and third quartile values of 41 (Q1 = 0%, Q3 = 96%), 50 (Q1 = 46%, Q3 = 74%), and 53% (Q1 = 36%, Q3 = 77%), respectively, demonstrating both the impact of these toxic exposures on cell signaling and the heterogeneity of response between cells. This approach will provide a valuable tool for the study of PTP dynamics, particularly in small, heterogeneous populations such as human biopsy specimens. PMID:23682679

Phillips, Ryan M.; Bair, Eric; Lawrence, David S.; Sims, Christopher E.; Allbritton, Nancy L.

2013-01-01

134

All optical switching in henna thin film  

NASA Astrophysics Data System (ADS)

The optical nonlinearity in henna (Lawson (2- hydroxyl-1,4 naphthoquinone) film was utilized to demonstrate all optical switching. The nonlinear absorption of the henna film was calculated by measuring the transmission of the laser beam ( ? = 488 nm) as a function of incident light intensities. The observed nonlinear absorption is attributed to a two-photon absorption process. The pump and probe technique was used to demonstrate all optical switching. The switching characteristics can be utilized to generate all-optical logic gates such as simple inverter switches (NOT) NOR, AND NAND logic functions.

Henari, Fryad Z.; Jasim, Khalil E.

2013-08-01

135

Catalytic reaction of cytokinin dehydrogenase: preference for quinones as electron acceptors  

Microsoft Academic Search

The catalytic reaction of cytokinin oxidase\\/dehydrogenase (EC 1.5.99.12) was studied in detail using the recombinant flavoenzyme from maize. Determination of the redox potential of the covalently linked flavin cofactor revealed a relatively high potential dictating the type of electron acceptor that can be used by the enzyme. Using 2,6-dichlorophenol indophenol, 2,3-dimethoxy-5-methyl-1,4-benzoquinone or 1,4-naphthoquinone as electron acceptor, turnover rates with N6-(2-isopentenyl)adenine

James T. English; Kristin D. Bilyeu; Ond?ej Novák; Pavel Pe?; Marek Šebela; Petr Galuszka; Marco W. Fraaije; Ivo Frébort; Jan Hrbá?; Jitka Frébortová

2004-01-01

136

The sensitizing capacity of chimaphilin, a naturally-occurring quinone.  

PubMed

Chimaphilin is a yellow naphthoquinone which occurs naturally in various chimaphila and Pyrola species. In Chimaphila umbellata (winter green) and C. maculata, it is a major constituent. Folk medicine recommends the leaves of Chimaphila species as a topical application to treat skin diseases. Since 1887, winter green is claimed to have caused dermatitis and to have been responsible for "idiosyncrasy". Experimental sensitization using the open epicutaneous as well as Freund's complete adjuvant technique has now revealed that chimaphilin is a moderate contact sensitizer. PMID:3191678

Hausen, B M; Schiedermair, I

1988-09-01

137

Antifungal and antioxidant activities of the phytomedicine pipsissewa, Chimaphila umbellata  

Microsoft Academic Search

Bioassay-guided fractionation of Chimaphila umbellata (L.) W. Bart (Pyrolaceae) ethanol extracts led to the identification of 2,7-dimethyl-1,4-naphthoquinone (chimaphilin) as the principal antifungal component. The structure of chimaphilin was confirmed by 1H and 13C NMR spectroscopy. The antifungal activity of chimaphilin was evaluated using the microdilution method with Saccharomyces cerevisiae (0.05mg\\/mL) and the dandruff-associated fungi Malassezia globosa (0.39mg\\/mL) and Malassezia restricta

Imelda J. Galván; Nadereh Mir-Rashed; Matthew Jessulat; Monica Atanya; Ashkan Golshani; Tony Durst; Philippe Petit; Virginie Treyvaud Amiguet; Teun Boekhout; Richard Summerbell; Isabel Cruz; John T. Arnason; Myron L. Smith

2008-01-01

138

MAPK regulation and caspase activation are required in DMNQ S-52 induced apoptosis in Lewis lung carcinoma cells  

Microsoft Academic Search

6-(1-Hydroxyimino-4-methylpentyl)5,8-dimethyoxy 1,4-naphthoquinone S-52 (DMNQ S-52) was reported to have cytotoxic activity against L1210 leukemia cells. In the present study, we investigated the apoptotic mechanism of DMNQ S-52 in vitro and in vivo in murine solid cancer cells. DMNQ S-52 exerted cytotoxicity against Lewis lung carcinoma (LLC) cells (IC50=12.3?M). DMNQ S-52 increased Annexin V positive cell population in a concentration-dependent manner.

Soo Jin Lee; Hiroaki Sakurai; Keiichi Koizumi; Gyu Yong Song; Yong Soo Bae; Hyung-Min Kim; Kyung-Sun Kang; Young-Joon Surh; Ikuo Saiki; Sung Hoon Kim

2006-01-01

139

Magnetic Field Effect: An Efficient Tool To Investigate The Mechanism Of Reactions Using Laser Flash Photolysis Technique  

NASA Astrophysics Data System (ADS)

Magnetic field effect combined with laser flash photolysis technique have been used to study the mechanism of interactions between two drug-like quinone molecules, Menadione (1,4-naphthoquinone, MQ) and 9, 10 Anthraquinone (AQ) with one of the DNA bases, Adenine in homogeneous acetonitrile/water and heterogeneous micellar media. A switchover in reaction mode from electron transfer to hydrogen abstraction is observed with MQ on changing the solvent from acetonitrile/water to micelle; whereas, AQ retains its mode of interaction towards Adenine as electron transfer in both the media due to its bulky structure compared to MQ.

Basu, Samita; Bose, Adity; Dey, Debarati

2008-04-01

140

Effects of rhinacanthin-C on function and expression of drug efflux transporters in Caco-2 cells.  

PubMed

Rhinacanthin-C is a bioactive naphthoquinone ester found in Rhinacanthus nasutus Kurz (Acanthaceae). This compound has potential therapeutic value as an anticancer and antiviral agent. The purposes of this study were to determine the effects of this compound on the function and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2), using the in vitro model of Caco-2 cells. The activities of P-gp and MRP2 were determined by following the intracellular accumulation of calcein and 5(6)-carboxy-2',7'-dichlorofluorescein in the uptake assays with fluorescence spectroscopy. The expression of P-gp after prolonged exposure was evaluated by flow cytometry with the use of a fluorescein isothiocyanate-conjugated anti-human P-gp antibody. Our results showed that the inhibitory effect of rhinacanthin-C was more potent toward P-gp than MRP2, and was reversible. Short-term exposure of Caco-2 cells with rhinacanthin-C (100 ?M) resulted in increase in P-gp expression without any significant change in its function. Extended exposure of Caco-2 cells to the naphthoquinone at the highest non-cytotoxic concentration (0.625 ?M) for 7 days had no effect on the expression and the function of P-gp. These findings suggested that rhinacanthin-C might raise the problem of herb-drug interaction when co-administered with other P-gp substrates. PMID:23742857

Wongwanakul, Ratjika; Vardhanabhuti, Nontima; Siripong, Pongpun; Jianmongkol, Suree

2013-09-01

141

Optimization and validation of spectrofluorimetric method for determination of cefadroxile and cefuroxime sodium in pharmaceutical formulations.  

PubMed

A simple, accurate, precise and validated spectrofluorimetric method is proposed for the determination of two cephalosporins, namely, cefadroxile (cefa) and cefuroxime sodium (cefu) in pharmaceutical formulations. The method is based on a reaction between cephalosporins with 1,2-naphthoquinone-4-sulfonate in alkaline medium, to form fluorescent derivatives that are extracted with chloroform and subsequently measured at 610 and 605 nm after excitation at 470 and 460 nm for cefa and cefu respectively. The optimum experimental conditions have been studied. Beer's law is obeyed over the concentrations of 20-70 ng/mL and 15-40 ng/mL for cefa and cefu, respectively. The detection limits were 4.46 ng/mL and 3.02 ng/mL with a linear regression correlation coefficient of 0.9984 and 0.998, and recoveries ranging 97.50-109.96% and 95.73-98.89% for cefa and cefu, respectively. The effects of pH, temperature, reaction time, 1,2-naphthoquinone-4-sulfonic concentration and extraction solvent on the determination of cefa and cefu, have been examined. The proposed method can be applied for the determination of cefa and cefu in pharmaceutical formulations in quality control laboratories. PMID:23345111

Elbashir, Abdalla A; Ahmed, Shazalia M A; Aboul-Enein, Hassan Y

2013-01-01

142

Alkannin/shikonin mixture from roots of Onosma echioides (L.) L.: extraction method study and quantification.  

PubMed

This work reports the extraction procedures of alkannin/shikonin mixture from roots of six populations of Onosma echioides, by means of three extraction techniques: Soxhlet extraction, maceration and rapid solid-liquid dynamic extraction (RSLDE). Five solvents with different polarity (hexane, petroleum ether, chloroform, ethyl acetate, methanol) were also studied. Analysis of the extracts was performed by an HPLC-DAD (diode array detector) system. The most efficient extraction technique was Soxhlet procedure using ethyl acetate for 6 h. Studied samples of O. echioides showed an alkannin/shikonin content in the range of 0.02-0.24 mg/kg. Other naphthoquinone derivatives (deoxyalkannin/deoxyshikonin and 5,8-dihydroxy-2-(4-methyl-6-oxo-5,6-dihydro-2H-pyran-2-yl)-[1,4]naphthoquinone and arnebin-6) were found for the first time in O. echioides and characterized in the extracts using HPLC-MS apparatus equipped with an ESI ionization source. PMID:18327849

Sagratini, Gianni; Cristalli, Gloria; Giardinà, Dario; Gioventù, Giorgio; Maggi, Filippo; Ricciutelli, Massimo; Vittori, Sauro

2008-04-01

143

Photoinduced reactions of para-quinones with bicyclopropylidene leading to diverse polycyclic compounds with spirocyclopropanes.  

PubMed

Photoinduced reactions of bicyclopropylidene (BCP) with para-quinones (p-quinones) including benzoquinones, naphthoquinones, and anthraquinones were found to proceed via different cycloaddition pathways and lead to diverse polycyclic products bearing spiropropyl moiety. Photocycloaddition of BCP with benzoquinones gave spirooxetanes as the primary products, which upon irradiation were able to rearrange into the spiro[4.5]deca-6,9-diene-2,8-diones as secondary photoproducts. Chemoselectivity of the photocycloaddition of BCP with naphthoquinones relies largely on the substitution groups linked to the C?C in between the two carbonyl groups to give different types of products. Photoreaction of BCP with 9,10-anthraquinone gave not only the spirooxetane product, but also a novel spiro[indan-1,1'-phthalan]-3'-one product whose formation might be initiated by a transannular attack of the C4 cyclopropyl radical to the para-carbonyl group. Mechanisms involved in the formation of diverse primary or secondary products in the photoreactions of BCP with p-quinones were proposed. Some of the photoreactions also hold potentials as useful synthetic protocols for important spiropolycyclic compounds such as sesquiterpenes. PMID:23692405

Wang, Wei; Zhang, Wen-Jie; Wang, Lei; Quah, Ching Kheng; Fun, Hoong-Kun; Xu, Jian-Hua; Zhang, Yan

2013-06-21

144

Pigment cell differentiation in sea urchin blastula-derived primary cell cultures.  

PubMed

The quinone pigments of sea urchins, specifically echinochrome and spinochromes, are known for their effective antioxidant, antibacterial, antifungal, and antitumor activities. We developed in vitro technology for inducing pigment differentiation in cell culture. The intensification of the pigment differentiation was accompanied by a simultaneous decrease in cell proliferation. The number of pigment cells was two-fold higher in the cells cultivated in the coelomic fluids of injured sea urchins than in those intact. The possible roles of the specific components of the coelomic fluids in the pigment differentiation process and the quantitative measurement of the production of naphthoquinone pigments during cultivation were examined by MALDI and electrospray ionization mass spectrometry. Echinochrome A and spinochrome E were produced by the cultivated cells of the sand dollar Scaphechinus mirabilis in all tested media, while only spinochromes were found in the cultivated cells of another sea urchin, Strongylocentrotus intermedius. The expression of genes associated with the induction of pigment differentiation was increased in cells cultivated in the presence of shikimic acid, a precursor of naphthoquinone pigments. Our results should contribute to the development of new techniques in marine biotechnology, including the generation of cell cultures producing complex bioactive compounds with therapeutic potential. PMID:24979272

Ageenko, Natalya V; Kiselev, Konstantin V; Dmitrenok, Pavel S; Odintsova, Nelly A

2014-07-01

145

Isolation and identification of an anti-tumor component from leaves of Impatiens balsamina.  

PubMed

We have previously shown that ethanol or chloroform extracts of the leaves of Impatiens balsamina (LIB) have anti-tumor activity against the human hepatocellular carcinoma cell line HepG2. The ethanol extracts were separated into five fractions according to polarity. An MTT assay indicated that two of the fractions had anti-tumor activity and that the petroleum ether fraction (PEF) was the most active. But the available quantities of both the PEF and chloroform fractions (CHF) were limited, precluding further study. The chloroform extract (CHE) shared almost all the same spots with the PEF and CHF and was plentiful enough to carry out further separations. Thus, the CHE was further separated into six sub-fractions (CHE 1 approximately 6) by column chromatography. A MTT assay showed that only the CHE2 fraction had a strong tumor inhibition ratio (IC(50) = 6.47+/-0.05 mg/L), which was superior to that of curcumin (IC(50) = 13.95+/-0.11 mg/L). However, TLC revealed that CHE2 was not pure and still contained two more components. After further separation and purification, followed by TLC and MTT assay confirmation, the final active component was isolated and identified as 2-methoxy-1,4-naphthoquinone by m.p., UV, MS and (13)C- and (1)H-NMR data. This is the first report demonstrating that 2-methoxy-1,4-naphthoquinone has intensive in vitro anti-tumor activity against HepG2 cells. PMID:18305414

Ding, Zhi-Shan; Jiang, Fu-Sheng; Chen, Ni-Pi; Lv, Gui-Yuan; Zhu, Cheng-Gang

2008-01-01

146

Antimalarial efficacy of dynamic compound of plumbagin chemical constituent from Plumbago zeylanica Linn (Plumbaginaceae) against the malarial vector Anopheles stephensi Liston (Diptera: Culicidae).  

PubMed

In the present investigation, the effective root compound of plumbagin of Plumbago zeylanica (Plumbaginaceae) was evaluated for chemical constituent and antimalarial effect against the fourth instar larvae of Anopheles stephensi Liston (Diptera). In the chromatographic analyses of root compound with Rf value of 0.788 and NMR analyses also revealed that the effective compound contain naphthoquinone plumbagin were identified as the major chemical constituent. Larval mortality was observed after 3 h of exposure period. The plumbagin compound showed remarkable larvicidal activity against A. stephensi (LC50 32.65 and LC9072.27 ppm). Histopathological effects of compound was observed in the treated larvae. Based on the results, the plumbagin compound of P. zeylanica can be considered as a new source of natural larvicide for the control of malarial vector. PMID:25028206

Pradeepa, Venkatraman; Sathish-Narayanan, Subbiah; Kirubakaran, Suyambulingam Arunachalam; Senthil-Nathan, Sengottayan

2014-08-01

147

Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway  

SciTech Connect

Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity.

Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng; Greig, Nigel H. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States)] [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Mattson, Mark P. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States) [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Camandola, Simonetta, E-mail: camandolasi@mail.nih.gov [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States)] [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States)

2013-04-19

148

REGIOSELECTIVE MULTICOMPONENT DOMINO REACTIONS PROVIDING RAPID AND EFFICIENT ROUTES TO FUSED ACRIDINES  

PubMed Central

Regioselective three-component reactions of aromatic aldehydes with indazol-5-amine and 2-hydroxy-1,4-naphthoquinone in HOAc under microwave irradiation have been developed. In this one-pot reaction, a series of new pyrazole-fused benzo[h]acridine derivatives with 1,2-diketone unit were synthesized with high chemical yields. The resulting pyrazole-fused acridines were employed to further react with aldehydes and ammonium acetate to give polycyclic oxazole-fused pyrazolo[3,4-j]acridines. The present green synthesis shows several advantages including operational simplicity and fast reaction rates, which makes it a useful and attractive process of library generation for drug discovery.

Zhang, Jin-Peng; Fan, Wei; Ding, Jie; Jiang, Bo; Tu, Shu-Jiang; Li, Guigen

2014-01-01

149

Unprecedented role of hydronaphthoquinone tautomers in biosynthesis.  

PubMed

Quinones and hydroquinones are among the most common cellular cofactors, redox mediators, and natural products. Here, we report on the reduction of 2-hydroxynaphthoquinones to the stable 1,4-diketo tautomeric form of hydronaphthoquinones and their further reduction by fungal tetrahydroxynaphthalene reductase. The very high diastereomeric and enantiomeric excess, together with the high yield of cis-3,4-dihydroxy-1-tetralone, exclude an intermediary hydronaphthoquinone. Labeling experiments with NADPH and NADPD corroborated the formation of an unexpected 1,4-diketo tautomeric form of 2-hydroxyhydronaphthoquinone as a stable intermediate. Similar 1,4-diketo tautomers of hydronaphthoquinones were established as products of the NADPH-dependent enzymatic reduction of other 1,4-naphthoquinones, and as substrates for different members of the superfamily of short-chain dehydrogenases. We propose an essential role of hydroquinone diketo tautomers in biosynthesis and detoxification processes. PMID:25047689

Husain, Syed Masood; Schätzle, Michael A; Lüdeke, Steffen; Müller, Michael

2014-09-01

150

Extensive phytochemical investigation of the polar constituents of Diospyros bipindensis Gürke traditionally used by Baka pygmies.  

PubMed

The water maceration and methanolic extract of the stem barks of Diospyros bipindensis, which is a medicinal plant used in Cameroon by Baka pygmies, revealed a complex high-performance liquid chromatography (HPLC) profile primarily composed of coumarin and naphthoquinone glycosides. The methanolic and apolar extracts also exhibited significant antifungal activity on a TLC bioautography assay against Candida albicans. HPLC-microfractionation in 96-well plates combined with bioautography enabled the rapid localization of the antifungal compound that was identified by HPLC-PDA and HPLC-MS analysis as plumbagin. These on-line structural information were also used to dereplicate four known compounds. The isolation of the polar constituents from the methanolic extract enabled the identification of eleven other compounds also present in the traditional preparation, nine of which are reported for the first time. The structures of those compounds were elucidated by UV, NMR and HR-MS analysis. PMID:24070618

Cesari, Ilaria; Queiroz, Emerson Ferreira; Favre-Godal, Quentin; Marcourt, Laurence; Caccialanza, Gabriele; Moundipa, Paul F; Brusotti, Gloria; Wolfender, Jean-Luc

2013-12-01

151

Stress-related polyketide metabolism of Dioncophyllaceae and Ancistrocladaceae.  

PubMed

The discovery of a novel biosynthetic pathway to isoquinoline alkaloids is described. The naphthylisoquinoline alkaloid dioncophylline A, one of the most prominent representatives of a new class of structurally and pharmacologically intriguing secondary metabolites, is shown to originate from acetate units, both molecular halves, the isoquinoline part and the naphthalene portion, being formed from identical polyketide precursors. All other tetrahydroisoquinoline alkaloids previously investigated, ultimately originate from aromatic amino acids. The novel pathway to isoquinoline alkaloids (hence acetogenic) was proved by feeding experiments with (13)C-labelled precursors administered to callus cultures of Triphyophyllum peltatum (Dioncophyllaceae), followed by NMR investigations using the potent cryoprobe methodology. The new pathway is largely stress-sensitive: upon exposure to chemical, biotic or physical stress, T. peltatum stops producing the isoquinoline part, so that the naphthalene moiety accumulates in the chemical form of naphthoquinones like plumbagin and droserone and the chiral tetralone isoshinanolone. PMID:11559737

Bringmann, G; Feineis, D

2001-10-01

152

[Chemical constituents from the seed coat of Juglans regia].  

PubMed

Fifteen compounds were isolated from the seed coat of Juglans regia by silica gel, MCI gel and Sephadex LH-20 gel column chromatography, as well as high preparative performance liquid chromatography. Their structures were identified as salidroside (1), (6S, 9S)-roseoside (2), (6S, 9R)-roseoside (3), blumenol C glucoside (4), byzantionoside B (5), 5-hydroxy-2-methoxy-1, 4-naphthoquinone (6), gallic acid (7), glycerol 1-(9Z-octadecenoate)-2-(9Z, 12Z-octadecadienoate)-3-(9Z, 12Z, 15Z-octadecatrienoate) (8), glycerol 1, 2, 3-tri-(9Z, 12Z-octadecadienoate) (9), glycerol 1, 2, 3-tri-(9Z, 12Z, 15Z-octadecatrienoate) (10), glycerol 1-hexadecanoate-2, 3-di-(9Z, 12Z-octadecadienoate) (11) on the basis of EI-MS, FAB-MS and NMR spectra. Moreover, 35 volatile compounds were identified by GC-MS. PMID:22860453

Liu, Chuanshui; Tai, Zhigang; Feng, Siquan; Fang, Yunshan; Cai, Le; Ding, Zhongtao

2012-05-01

153

Diels-Alder reactions of 4-alkenylthiazoles: a new approach to thiazole functionalization.  

PubMed

Somewhat unexpectedly, the computed highest occupied molecular orbital (HOMO) energies of some 4-alkenylthiazoles afforded values close to those calculated for the Danishefsky-Kitahara and Rawal dienes. In fact, 4-alkenylthiazoles behave as all-carbon dienes in Diels-Alder reactions with the participation of the formal C-C double bond of the thiazole ring and the side-chain double bond. The reactions with N-substituted maleimides, maleic anhydride, and naphthoquinone take place with high levels of stereocontrol to give the corresponding endo-cycloadducts in good to excellent yields. Depending on the dienophile, the cycloadduct further transforms under the reaction conditions through either a 1,3-hydrogen shift, dehydrogenation, or an ene reaction or Michael addition with another molecule of dienophile. These unprecedented results open new synthetic perspectives for the functionalization of the thiazole ring. PMID:17316049

Alajarín, Mateo; Cabrera, José; Pastor, Aurelia; Sánchez-Andrada, Pilar; Bautista, Delia

2007-03-16

154

Laser flash photolysis and magnetic-field-effect studies on interaction of thymine and thymidine with menadione: role of sugar in controlling reaction pattern  

NASA Astrophysics Data System (ADS)

The magnetic field effect (MFE) in conjunction with laser flash photolysis has been used for the study of the interaction of one of the small drug like quinone molecules, 2-methyl, 1,4-naphthoquinone, commonly known as menadione (MQ), with one of the DNA bases, thymine (THN), and its corresponding nucleoside, thymidine (THDN), in acetonitrile (ACN) and sodium dodecylsulfate (SDS) micelles. It has been observed that THN undergoes electron transfer (ET) and hydrogen (H) abstraction with MQ, while THDN undergoes only H abstraction in both the media. However, our earlier studies showed that a purine base, adenine (ADN), and its nucleoside, 2'-deoxyadenosine (ADS), undergo ET in ACN and H abstraction in SDS. Here we have attempted to explain the differences in the reactions of these DNA bases with MQ. We also reveal the crucial role of a sugar unit in altering the behavior of purine and pyrimidine bases with respect to ET and H abstraction.

Bose, Adity; Dey, Debarati; Basu, Samita

2008-04-01

155

Simultaneous identification of amphetamine and its derivatives in urine using HPLC-UV.  

PubMed

An HPLC-UV method for the simultaneous identification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in urine is described. It includes a rapid extraction procedure of the 4 analogs from urine using Extrelut 3 columns, derivatization with sodium 1,2-naphthoquinone-4-sulphonate (NQS) to obtain highly chromophoric UV-VIS derivatives, and a final HPLC analysis using an ion-pair reversed-phase technique with eluent monitoring at 480 nm. Structural characterization of the derivatives obtained by mass spectrometry is reported. Recoveries of the amphetamines were in the range 80-85% at concentrations of 300 ng/ml. Practical detection limits were 40-60 ng/ml (S/N ratio = 10) for all derivatives. The chromatographic peaks of the NQS derivatized amphetamines are fairly narrow and well resolved. The method is simple, rapid, quite sensitive, and specific for convenient confirmation of preliminary positive results obtained with immunoassays. PMID:8097107

Tedeschi, L; Frison, G; Castagna, F; Giorgetti, R; Ferrara, S D

1993-01-01

156

Isolation of an antimicrobial compound from Impatiens balsamina L. using bioassay-guided fractionation.  

PubMed

By using brine shrimp (Artemia salina) lethality test-guided fractionation, a single bioactive compound (LC(50)=26 ppm) was isolated from the 95% ethanol extract of the dried aerial parts of Impatiens balsamina L. and subsequently identified as 2-methoxy-1,4-naphthoquinone (MNQ). The structure of MNQ was confirmed by UV, FT-IR, MS, and 1-and 2-D NMR spectroscopy. The antimicrobial activity of MNQ was evaluated using 12 bacterial and eight fungal strains. Five gram-positive and two gram-negative bacteria as well as all eight fungi (including multi-drug resistant strains) tested were highly sensitive to MNQ. A tea prepared according to traditional methods was found to contain sufficient MNQ to account for its antimicrobial properties. PMID:11746859

Yang, X; Summerhurst, D K; Koval, S F; Ficker, C; Smith, M L; Bernards, M A

2001-12-01

157

Antipruritic and antidermatitic effect of extract and compounds of Impatiens balsamina L. in atopic dermatitis model NC mice.  

PubMed

We examined the effects of a 35% ethanol extract (IB) from the petals of Impatiens balsamina L. and the principal active compounds from IB on chronic and serious pruritus and the development of dermatitis using NC mice, a model of atopic dermatitis. IB at 100 mg/kg significantly inhibited serious scratching behaviour in the NC mouse with established dermatitis when administered i.v. 1 h before, or p.o. 24 h before the measurement. A 10 microg/kg dose of kaempferol 3-rutinoside and 2-hydroxy-1,4-naphthoquinone (lawsone) isolated from IB also inhibited scratching behaviour in the NC mouse with established dermatitis. When 4-week-old NC mice with no symptoms were administered orally 100 mg/kg/day of IB until 13 weeks of age, protection was also noted against scratching behaviour during the development of dermatitis. IB was effective for the prevention and treatment of atopic dermatitis. PMID:11536380

Oku, H; Ishiguro, K

2001-09-01

158

Synthesis, characterization and molecular structures of homologated analogs of 2-bromo-3-(n-alkylamino)-1,4-napthoquinone  

NASA Astrophysics Data System (ADS)

Four analogues of 2-bromo-3-(n-alkylamino)-1,4-napthoquinone (where n-alkyl is methyl in L-1Br, ethyl in L-2Br, propyl in L-3Br and butyl in L-4Br) are synthesized and characterized. A reaction mechanism is proposed for the formation of L-1Br to L-4Br from the starting material 2,3-dibromo-1,4-naphthoquinone. The ?NH frequency in the FT-IR spectra is affected by the intramolecular hydrogen bonding in L-1Br to L-4Br and is observed ˜3267 cm-1 in L-2Br. A shift of ˜25 cm-1 is observed in the ?CBr frequency in all the compounds as compared to 2,3-dibromo-1,4-naphthoquinone (627 cm-1). A broad charge transfer band is observed between 400 and 600 nm in the UV-Vis spectra, which imparts red colour to all the compounds. Molecular structures of L-2Br and L-3Br were studied by single crystal X-ray diffraction studies. Molecules of L-2Br crystallize in Pca21, whereas the molecule L-3Br crystallizes in the P-1 space group. Molecules of L-2Br forms a polymeric chain through NH⋯O interaction and forms beautiful butterfly like arrangement of molecules when viewed down the 'a' axis. Ladder like polymeric chain of molecules is observed in L-3Br via CH⋯O and NH⋯O interactions. Every alternating neighbouring chains of L-3Br, show ?-? stacking interactions between the quinonoid rings of the molecules, however this interaction is not observed in L-2Br.

Salunke-Gawali, Sunita; Pawar, Omkar; Nikalje, Milind; Patil, Rishikesh; Weyhermüller, Thomas; Puranik, Vedavati G.; Badireenath Konkimalla, V.

2014-01-01

159

Anti-Tumor Effects of Novel 5-O-Acyl Plumbagins Based on the Inhibition of Mammalian DNA Replicative Polymerase Activity  

PubMed Central

We previously found that vitamin K3 (menadione, 2-methyl-1,4-naphthoquinone) inhibits the activity of human mitochondrial DNA polymerase ? (pol ?). In this study, we focused on plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), and chemically synthesized novel plumbagins conjugated with C2:0 to C22:6 fatty acids (5-O-acyl plumbagins). These chemically modified plumbagins enhanced mammalian pol inhibition and their cytotoxic activity. Plumbagin conjugated with chains consisting of more than C18-unsaturated fatty acids strongly inhibited the activities of calf pol ? and human pol ?. Plumbagin conjugated with oleic acid (C18:1-acyl plumbagin) showed the strongest suppression of human colon carcinoma (HCT116) cell proliferation among the ten synthesized 5-O-acyl plumbagins. The inhibitory activity on pol ?, a DNA replicative pol, by these compounds showed high correlation with their cancer cell proliferation suppressive activity. C18:1-Acyl plumbagin selectively inhibited the activities of mammalian pol species, but did not influence the activities of other pols and DNA metabolic enzymes tested. This compound inhibited the proliferation of various human cancer cell lines, and was the cytotoxic inhibitor showing strongest inhibition towards HT-29 colon cancer cells (LD50?=?2.9 µM) among the nine cell lines tested. In an in vivo anti-tumor assay conducted on nude mice bearing solid tumors of HT-29 cells, C18:1-acyl plumbagin was shown to be a promising tumor suppressor. These data indicate that novel 5-O-acyl plumbagins act as anti-cancer agents based on mammalian DNA replicative pol ? inhibition. Moreover, the results suggest that acylation of plumbagin is an effective chemical modification to improve the anti-cancer activity of vitamin K3 derivatives, such as plumbagin. PMID:24520419

Kawamura, Moe; Kuriyama, Isoko; Maruo, Sayako; Kuramochi, Kouji; Tsubaki, Kazunori; Yoshida, Hiromi; Mizushina, Yoshiyuki

2014-01-01

160

Molecular modeling and docking studies of O-succinylbenzoate synthase of M. tuberculosis--a potential target for antituberculosis drug design.  

PubMed

Menaquinone is a lipid-soluble naphthoquinone that is essential for various pivotal functions of bacteria. Naphthoquinone is synthesized from chorismate of the shikimate pathway in microorganisms. Due to its absence in humans and animals, menaquinone biosynthesis has been an attractive target for development of antibiotics against a number of important microbial pathogens, such as Mycobacterium tuberculosis (Mtb). In shikimate pathway, O-succinylbenzoate synthase (OSBS) plays a major role and is one of the major potential drug targets. For Mtb-OSBS, a systematic study was conducted to get an insight about Mtb-OSBS enzyme and the corresponding inhibitors using in silico methods. The 3-D model of Mtb-OSBS was built using structure coordinates of Thermobifida fusca. O-succinylbenzoate synthase, the model, was further refined. The active site amino acids have been identified by comparing the template sequence with the Mtb-OSBS sequence. We identified that Lys(108), Asn(140), Asp(138), Lys(110), Glu(189), Ser(236), Asp(188), Arg(27), Tyr(52), and Ser(237) are highly conserved, and these may play a vital role as active residues, similar to that in template protein. As per the competitive binding of substrate (2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC)), we screened the SHCHC through AutoDock 4.0. The SHCHC molecule was further modified structurally and optimized through PRODRG server. Docking of the 12 lead molecules for best interactions with Mtb-OSBS has given an insight that all the lead molecules have shown interactions with active site amino acids of Mtb-OSBS. MD simulation analysis report has shown the stable conformation annotations of Mtb-OSBS. These hypothetical studies create another way to develop more potential drugs against the deadly mycobacterium. PMID:24203275

Pulaganti, Madhusudana; Banaganapalli, Babajan; Mulakayala, Chaitanya; Chitta, Suresh Kumar; C M, Anuradha

2014-02-01

161

Synthesis of New Chlorin?e6 Trimethyl and Protoporphyrin?IX Dimethyl Ester Derivatives and Their Photophysical and Electrochemical Characterizations.  

PubMed

In view of increasing demands for efficient photosensitizers for photodynamic therapy (PDT), we herein report the synthesis and photophysical characterizations of new chlorin?e6 trimethyl ester and protoporphyrin?IX dimethyl ester dyads as free bases and Zn(II) complexes. The synthesis of these molecules linked at the ?-pyrrolic positions to pyrano[3,2-c]coumarin, pyrano[3,2-c]quinolinone, and pyrano[3,2-c]naphthoquinone moieties was performed by using the domino Knoevenagel hetero Diels-Alder reaction. The ?-methylenechromanes, ?-methylenequinoline, and ortho-quinone methides were generated in situ from a Knoevenagel reaction of 4-hydroxycoumarin, 4-hydroxy-6-methylcoumarin, 4-hydroxy-N-methylquinolinone, and 2-hydroxy-1,4-naphthoquinone, respectively, with paraformaldehyde in dioxane. All the dyads as free bases and as Zn(II) complexes were obtained in high yields. All new compounds were fully characterized by 1D and 2D NMR techniques, UV/Vis spectroscopy, and HRMS. Their photophysical properties were evaluated by measuring the fluorescence quantum yield, the singlet oxygen quantum yield by luminescence detection, and also the triplet lifetimes were correlated by flash photolysis and intersystem crossing (ISC) rates. The fluorescence lifetimes were measured by a time-correlated single photon count (TCSPC) method, fluorescence decay associated spectra (FDAS), and anisotropy measurements. Magnetic circular dichroism (MCD) and circular dichroism (CD) spectra were recorded for one Zn(II) complex in order to obtain information, respectively, on the electronic and conformational states, and interpretation of these spectra was enhanced by molecular orbital (MO) calculations. Electrochemical studies of the Zn(II) complexes were also carried out to gain insights into their behavior for such applications. PMID:25171181

Menezes, José C J M D S; Faustino, M Amparo F; de Oliveira, Kleber T; Uliana, Marciana P; Ferreira, Vitor F; Hackbarth, Steffen; Röder, Beate; Teixeira Tasso, Thiago; Furuyama, Taniyuki; Kobayashi, Nagao; Silva, Artur M S; Neves, M Graça P M S; Cavaleiro, José A S

2014-10-13

162

Plumbagin inhibits prostate cancer development in TRAMP mice via targeting PKC?, Stat3 and neuroendocrine markers.  

PubMed

Plumbagin (PL), 5-hydroxy-2-methyl-1,4-naphthoquinone, is a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L. (also known as chitrak). PL has also been found in Juglans regia (English Walnut), Juglans cinerea (whitenut) and Juglans nigra (blacknut). The roots of P. zeylanica have been used in Indian and Chinese systems of medicine for more than 2500 years for the treatment of various types of ailments. We were the first to report that PL inhibits the growth and invasion of hormone refractory prostate cancer (PCa) cells [Aziz,M.H. et al. (2008) Plumbagin, a medicinal plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer. Cancer Res., 68, 9024-9032.]. Now, we present that PL inhibits in vivo PCa development in the transgenic adenocarcinoma of mouse prostate (TRAMP). PL treatment (2 mg/kg body weight i.p. in 0.2 ml phosphate-buffered saline, 5 days a week) to FVB-TRAMP resulted in a significant (P < 0.01) decrease in prostate tumor size and urogenital apparatus weights at 13 and 20 weeks. Histopathological analysis revealed that PL treatment inhibited progression of prostatic intraepithelial neoplasia (PIN) to poorly differentiated carcinoma (PDC). No animal exhibited diffuse tumor formation in PL-treated group at 13 weeks, whereas 75% of the vehicle-treated mice elicited diffuse PIN and large PDC at this stage. At 20 weeks, 25% of the PL-treated animals demonstrated diffuse PIN and 75% developed small PDC, whereas 100% of the vehicle-treated mice showed large PDC. PL treatment inhibited expression of protein kinase C epsilon (PKC?), signal transducers and activators of transcription 3 phosphorylation, proliferating cell nuclear antigen and neuroendocrine markers (synaptophysin and chromogranin-A) in excised prostate tumor tissues. Taken together, these results further suggest PL could be a novel chemopreventive agent against PCa. PMID:22976928

Hafeez, Bilal Bin; Zhong, Weixiong; Mustafa, Ala; Fischer, Joseph W; Witkowsky, Olya; Verma, Ajit K

2012-12-01

163

Anti-tumor effects of novel 5-O-acyl plumbagins based on the inhibition of mammalian DNA replicative polymerase activity.  

PubMed

We previously found that vitamin K3 (menadione, 2-methyl-1,4-naphthoquinone) inhibits the activity of human mitochondrial DNA polymerase ? (pol ?). In this study, we focused on plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), and chemically synthesized novel plumbagins conjugated with C2:0 to C22:6 fatty acids (5-O-acyl plumbagins). These chemically modified plumbagins enhanced mammalian pol inhibition and their cytotoxic activity. Plumbagin conjugated with chains consisting of more than C18-unsaturated fatty acids strongly inhibited the activities of calf pol ? and human pol ?. Plumbagin conjugated with oleic acid (C18:1-acyl plumbagin) showed the strongest suppression of human colon carcinoma (HCT116) cell proliferation among the ten synthesized 5-O-acyl plumbagins. The inhibitory activity on pol ?, a DNA replicative pol, by these compounds showed high correlation with their cancer cell proliferation suppressive activity. C18:1-Acyl plumbagin selectively inhibited the activities of mammalian pol species, but did not influence the activities of other pols and DNA metabolic enzymes tested. This compound inhibited the proliferation of various human cancer cell lines, and was the cytotoxic inhibitor showing strongest inhibition towards HT-29 colon cancer cells (LD50 = 2.9 µM) among the nine cell lines tested. In an in vivo anti-tumor assay conducted on nude mice bearing solid tumors of HT-29 cells, C18:1-acyl plumbagin was shown to be a promising tumor suppressor. These data indicate that novel 5-O-acyl plumbagins act as anti-cancer agents based on mammalian DNA replicative pol ? inhibition. Moreover, the results suggest that acylation of plumbagin is an effective chemical modification to improve the anti-cancer activity of vitamin K3 derivatives, such as plumbagin. PMID:24520419

Kawamura, Moe; Kuriyama, Isoko; Maruo, Sayako; Kuramochi, Kouji; Tsubaki, Kazunori; Yoshida, Hiromi; Mizushina, Yoshiyuki

2014-01-01

164

Electron transfer capacity dependence of quinone-mediated Fe(III) reduction and current generation by Klebsiella pneumoniae L17.  

PubMed

Quinone groups in exogenous electron shuttles can accelerate extracellular electron transfer (EET) from bacteria to insoluble terminal electron acceptors, such as Fe(III) oxides and electrodes, which are important in biogeochemical redox processes and microbial electricity generation. However, the relationship between quinone-mediated EET performance and electron-shuttling properties of the quinones remains incompletely characterized. This study investigates the effects of a series of synthetic quinones (SQs) on goethite reduction and current generation by a fermenting bacterium Klebsiella pneumoniae L17. In addition, the voltammetric behavior and electron transfer capacities (ETCs) of SQ, including electron accepting (EAC) and donating (EDC) capacities, is also examined using electrochemical methods. The results showed that SQ can significantly increase both the Fe(III) reduction rates and current outputs of L17. Each tested SQ reversibly accepted and donated electrons as indicated by the cyclic voltammograms. The EAC and EDC results showed that Carmine and Alizarin had low relative capacities of electron transfer, whereas 9,10-anthraquinone-2,6-disulfonic acid (AQDS), 2-hydroxy-1,4-naphthoquinone (2-HNQ), and 5-hydroxy-1,4-naphthoquinone (5-HNQ) showed stronger relative ETC, and 9,10-anthraquinone-2-carboxylic acid (AQC) and 9,10-anthraquinone-2-sulfonic acid (AQS) had high relative ETC. Enhancement of microbial goethite reduction kinetics and current outputs by SQ had a good linear relationship with their ETC, indicating that the effectiveness of quinone-mediated EET may be strongly dependent on the ETC of the quinones. Therefore, the presence of quinone compounds and fermenting microorganisms may increase the diversity of microbial populations that contribute to element transformation in natural environments. Moreover, ETC determination of different SQ would help to evaluate their performance for microbial EET under anoxic conditions. PMID:23461838

Li, Xiaomin; Liu, Liang; Liu, Tongxu; Yuan, Tian; Zhang, Wei; Li, Fangbai; Zhou, Shungui; Li, Yongtao

2013-06-01

165

Chemoprevention of skin cancer: effect of Lawsonia inermis L. (Henna) leaf powder and its pigment artifact, lawsone in the Epstein- Barr virus early antigen activation assay and in two-stage mouse skin carcinogenesis models.  

PubMed

In continuation of our studies with chemoprevention potential of plant-derived naphthoquinone derivatives, leaf powder of the medicinal plant Lawsonia inermis L, commonly known as 'henna', was evaluated by its inhibition of the Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Lawsone (2-hydroxy- 1,4-naphthoquinone), the reddish orange pigment artifact formed during the extraction or preparation of the dye from henna leaves and believed to be the active component, was also assessed in this in vitro assay. Both showed a profound inhibition (>88%) of EBV-EA activation. In the in vivo two-stage mouse skin carcinogenesis study using UV-B radiation for initiation and TPA for tumor promotion, oral feeding of henna (0.0025%) in drinking water ad libitum decreased tumor incidence by 66% and multiplicity by 40% when compared to the positive control at 10 weeks of treatment. Similarly, in the above mouse model, orally fed lawsone (0.0025%) decreased tumor incidence by 72% and multiplicity by 50%. The tumor inhibitory trend continued throughout the 20-week test period. Similar antitumor activities were observed when henna (0.5 mg/ml) was applied topically on the back skin in the UV-B initiated, TPA promoted and peroxynitrite initiated, TPA promoted mouse skin carcinogenesis models. Topically applied lawsone (0.015 mg/ml) also exhibited similar protection against tumor formation in the 7,12-dimtehylbenz(a)anthracene induced and TPA promoted skin cancer in mice. Also, there was a delay of 1 to 2 weeks in tumor appearance in both henna and lawsone treated groups compared to control in all three test models. This study ascertains the skin cancer chemopreventive activity of henna leaf powder and lawsone when administered by either oral (through drinking water) or topical (by application on the back skin) routes. Further, it emphasizes the need for the evaluation of these henna-derived green chemopreventive candidates in combination with currently used sunscreen agents for complementary anticancer potential against UV-induced skin carcinogenesis. PMID:23848207

Kapadia, Govind J; Rao, G Subba; Sridhar, Rajagopalan; Ichiishi, Eiichiro; Takasaki, Midori; Suzuki, Nobutaka; Konoshima, Takao; Iida, Akira; Tokuda, Harukuni

2013-12-01

166

Inhibition of cholinesterase activity by extracts, fractions and compounds from Calceolaria talcana and C. integrifolia (Calceolariaceae: Scrophulariaceae).  

PubMed

Extracts, fractions and compounds from Calceolaria talcana and C. integrifolia exhibited strong inhibitory effects of the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes using the in vitro Ellman's method. The most active samples were from the ethyl acetate extract, which caused a mixed-type inhibition against AChE (69.8% and 79.5% at 100 and 200 ?g/ml, respectively) and against BChE (98.5% and 99.8% at 100 and 200 ?g/ml, respectively) and its major components verbascoside 8 (50.9% and 70.0% at 200 ?g/ml, against AChE and BChE, respectively), martynoside 9, and fraction F-7 (which corresponds to a mixture of 8, 9, and other phenylethanoids and phenolics that remain unidentified) (80.2% and 85.3% at 100 and 200 ?g/ml, against AChE, respectively and 99.1% and 99.7% at 100 and 200 ?g/ml, against BChE, respectively) inhibited the acetylcholinesterase enzyme competitively. The most polar fraction F-5 from n-hexane extract (a mixture of naphthoquinones: 2-hydroxy-3-(1,1-dimethylallyl-1,4-naphthoquinone) 6, ?-dunnione 7 and other polar compounds that remain unidentified) showed a mixed-type inhibition (71.5% and 72.1% against AChE and BChE at 200 ?g/ml, respectively). Finally, the methanol-soluble residue presented a complex, mixed-type inhibition (39.9% and 67.9% against AChE and BChE at 200 ?g/ml, respectively). The mixture F-3 with diterpenes was obtained from the n-hexane extract: (1,10-cyclopropyl-9-epi-ent-isopimarol) 1, 19-?-hydroxy-abietatriene 2, and F-4 a mixture of triterpenes ?-lupeol 3, ?-sitosterol 4, ursolic acid 5 together with a complex mixture of terpenes that did not show activity. In summary, extracts and natural compounds from C. talcana and C. integrifolia were isolated, identified and characterized as cholinesterase inhibitors. PMID:24416779

Cespedes, Carlos L; Muñoz, Evelyn; Salazar, Juan R; Yamaguchi, Lydia; Werner, Enrique; Alarcon, Julio; Kubo, Isao

2013-12-01

167

New spectrofluorimetric method for determination of cephalosporins in pharmaceutical formulations.  

PubMed

Simple, accurate and sensitive spectrofluorimetric method has been proposed for the determination of three cephalosporins, namely; cefixime (cefi), cephalexine (ceph), cefotaxime sodium (cefo) in pharmaceutical formulations. The method is based on a reaction between cephalosporins with 1, 2-naphthoquinone-4-sulfonic (NQS) in alkaline medium, at pH values of 12.0 for cefi and 13.0 for ceph and cefo to give highly fluorescent derivatives extracted with chloroform and subsequently measured at 600,580 and 580 nm after excitation at 520,455 and 490 nm for cefi, ceph and cefo respectively. The optimum experimental conditions have been studied. Beer's law is obeyed over the concentrations of 10-35 ng/mL, 10-60 ng/mL and 20-45 ng/mL for cefi,ceph and cefo, respectively. The detection limits were 2.02 ng/mL, 2.09 ng/mL and 2.30 ng/mL for cefi, ceph and cefo, respectively, with a linear regression correlation coefficient of 0.9987, 0.9995 and 0.9991 and recoveries in range from 98.5-107.04, 95.17-101.00 and 95.00-109.55% for cefi, ceph and cefo, respectively. This method is simple and can be applied for the determination of cefi, ceph and cefo in pharmaceutical formulations in quality control laboratories. PMID:22160361

Elbashir, Abdalla A; Ahmed, Shazalia M Ali; Aboul-Enein, Hassan Y

2012-05-01

168

New spectrophotometric methods for the determination of moxifloxacin in pharmaceutical formulations.  

PubMed

Two rapid, simple and sensitive spectrophotometric methods for the quantitative analysis of moxifloxacin (MOX) in pharmaceutical formulations have been described. The first method (A) involves reaction of MOX with 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline medium (pH 11.0) which results in an orange-coloured product exhibiting maximum absorption (lambda(max)) at 411 nm. The second method (B) is based on the oxidation of the MOX with a known excess of cerium (IV) sulfate and the residual oxidant is determined by treating with a fixed amount of methyl orange, and measuring the absorbance at 507 nm. The molar absorptivities for methods A and B were 4.9 x 10(3) and 6.5 x 10(4) L mol(-1) cm(-1), respectively. Under the optimized reaction conditions, Beer's law correlation of the absorbance with MOX concentration was obtained in the range of 2.5-20 and 0.5-30 microgmL(-1) for method A and B respectively. The intra-day precision expressed as relative standard deviation (RSD) was < 1.6% for both methods. The methods were validated in terms of accuracy and precision and were successfully applied to the determination of MOX in its pharmaceutical dosage form. The proposed methods are useful for routine analysis of MOX in quality control laboratories. PMID:23841346

Elbashir, Abdalla A; Ebraheem, Sara A M; Elwagee, Alawia H E; Aboul-Enein, Hassan Y

2013-01-01

169

Spectrophotometric determination of boron based on charge transfer reaction.  

PubMed

Boron determination by a charge transfer spectrophotometric method is described. Accompanied the reaction, a charge transfer complex can be formed by lysine with sodium 1, 2-naphthoquinone-4-sulfonate and boron in alkaline solution (pH 12.00). Subsequently, a new reaction mechanism has been proposed and discussed. The absorbance at the maximal absorption wavelength is 574 nm and boron concentration agrees well with Beer's law in a range of 2.16-43.24 ?g mL(-1). The linear regression equation is A=-0.01867+0.01326C (?g mL(-1)), with a linearly correlation coefficient of 0.9935. The relative standard deviation (R.S.D.) of eleven parallel determinations is 2.1% with a detection limit (3?/k) of 2.00 ?g mL(-1). The recovery ranges from 96.4% to 104.5% with the satisfactory results. This method has been successfully applied to determine boron in pharmaceutical samples directly. PMID:21530377

Ma, Linjin; Zhang, Zhenxuan; Li, Quanmin

2011-08-01

170

Synthesis and biological evaluation of pyrazolylnaphthoquinones as new potential antiprotozoal and cytotoxic agents.  

PubMed

The importance of American trypanosomiasis (Chagas' disease) in human pathology is widely known. The prognosis of this disease is poor and the choice of effective medicines limited, thus study of new drugs is absolutely necessary. In this work, the activities of three new pyrazolylnaphthoquinones, heterocyclic naphthoquinones bearing 3-aminopyrazole rings, were evaluated on Trypanosoma cruzi, the etiological agent of Chagas' disease. These activities were compared with those of three 5-aminoisoxazole analogues. In addition, since these compounds belong to a family of antiprotozoal and cytotoxic/antitumor agents, the activities of all six against Plasmodium falciparum, Trypanosoma brucei rhodesiense, and murine L-6 cells were also investigated. In the biological tests, five of the compounds showed significant in vitro trypanocidal activities against T. cruzi, with activities similar to that of benznidazole. Two of the 5-aminoisoxazole analogues also showed good activities, in one case highly selective, against the K1 and NF54 strains of P. falciparum (IC(50)<0.12 microg mL(-1)). Three of the compounds were cytotoxic to murine L-6 cells (IC(50)=0.21-0.50 microg mL(-1)). The results suggested that the three pyrazolylnaphthoquinones and one of the 5-aminoisoxazole analogues could be starting points for lead optimization programs against T. cruzi and P. falciparum, respectively. PMID:12512078

Sperandeo, Norma R; Brun, Reto

2003-01-01

171

Multitarget Drug Design Strategy: Quinone-Tacrine Hybrids Designed To Block Amyloid-? Aggregation and To Exert Anticholinesterase and Antioxidant Effects.  

PubMed

We report the identification of multitarget anti-Alzheimer compounds designed by combining a naphthoquinone function and a tacrine fragment. In vitro, 15 compounds displayed excellent acetylcholinesterase (AChE) inhibitory potencies and interesting capabilities to block amyloid-? (A?) aggregation. The X-ray analysis of one of those compounds in complex with AChE allowed rationalizing the outstanding activity data (IC50 = 0.72 nM). Two of the compounds showed negligible toxicity in immortalized mouse cortical neurons Neuro2A and primary rat cerebellar granule neurons. However, only one of them was less hepatotoxic than tacrine in HepG2 cells. In T67 cells, both compounds showed antioxidant activity, following NQO1 induction. Furthermore, in Neuro2A, they were able to completely revert the decrease in viability induced by A?. Importantly, they crossed the blood-brain barrier, as demonstrated in ex vivo experiments with rats. When ex vivo results were combined with in vitro studies, these two compounds emerged to be promising multitarget lead candidates worthy of further pursuit. PMID:25259726

Nepovimova, Eugenie; Uliassi, Elisa; Korabecny, Jan; Peña-Altamira, Luis Emiliano; Samez, Sarah; Pesaresi, Alessandro; Garcia, Gregory E; Bartolini, Manuela; Andrisano, Vincenza; Bergamini, Christian; Fato, Romana; Lamba, Doriano; Roberti, Marinella; Kuca, Kamil; Monti, Barbara; Bolognesi, Maria Laura

2014-10-23

172

Superoxide targets calcineurin signaling in vascular endothelium  

SciTech Connect

Superoxide emerges as key regulatory molecule in many aspects of vascular physiology and disease, but identification of superoxide targets in the vasculature remains elusive. In this work, we investigated the possibility of inhibition of protein phosphatase calcineurin by superoxide in endothelial cells. We employed a redox cycler 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) to generate superoxide inside the cells. DMNQ caused inhibition of cellular calcineurin phosphatase activity, which was reversible upon DMNQ removal. Inhibition was suppressed by pre-incubating the cells with copper/zinc superoxide dismutase (Cu,ZnSOD). In addition, reducing cellular Cu,ZnSOD activity by diethylthiocarbamic acid treatment resulted in calcineurin inhibition and enhanced sensitivity to DMNQ. Further, we could show that DMNQ inhibits calcineurin-dependent nuclear translocation and transcriptional activation of NFAT transcription factor, and Cu,ZnSOD or superoxide scavenger Tiron reduced the inhibition. Thus, superoxide generation in endothelial cells results in inhibition of calcineurin signaling, which could have important pathophysiological implications in the vasculature.

Namgaladze, Dmitry [Faculty of Medicine, Institute of Biochemistry I, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt (Germany)]. E-mail: dmitry@zbc.kgu.de; Shcherbyna, Ivanna [Faculty of Biology, University of Konstanz, D-78457 Konstanz (Germany); Kienhoefer, Joachim [Faculty of Biology, University of Konstanz, D-78457 Constance (Germany); Hofer, H. Werner [Faculty of Biology, University of Konstanz, D-78457 Konstanz (Germany); Ullrich, Volker [Faculty of Biology, University of Konstanz, D-78457 Constance (Germany)

2005-09-09

173

New tissue schizontocidal antimalarial drugs  

PubMed Central

Over 700 causal prophylactic and radical curative antimalarial drugs have been discovered during the screening of approximately 4000 chemical compounds in rodent and simian malaria models. Causal prophylactic activity in the Plasmodium berghei—rodent model was demonstrated by 10 distinct groups of chemicals: 1) tetrahydrofolate dehydrogenase inhibitors, 2) naphthoquinones, 3) dihydroacridinediones, 4) tetrahydrofurans, 5) guanylhydrazones, 6) analogues of clopidol, 7) quinoline esters, 8) dibenzyltetrahydro-pyrimidines, 9) 6-aminoquinolines, 10) 8-aminoquinolines. Of the causal prophylactic compounds, only the 6- and 8-aminoquinolines were capable of curing persistent exoerythrocytic infections of P. cynomolgi in rhesus monkeys. The 6-aminoquinolines were substantially less active than primaquine. This report describes a series of 4-methyl-5-phenoxy-6-methoxy-8-aminoquinolines, which are potent blood schizontocides and radical curative drugs. The most active member of this series, 4-methyl-5-(3-trifluoromethylphenoxy)-6-methoxy-8-[(4-amino-1-methylbutyl)| amino]quinoline succinate (WR 225448), was 5 times more active than primaquine in curing persistent exoerythrocytic infections of P. cynomolgi in rhesus monkeys. As a blood schizontocide, WR 225448 was effective in animal models against P. berghei, P. cynomolgi, P. vivax, and both drug-sensitive and drug-resistant strains of P. falciparum. WR 225448 was also more toxic than primaquine in rats on subacute (28-day) administration. PMID:6976854

Davidson, David E.; Ager, Arba L.; Brown, John L.; Chapple, Frank E.; Whitmire, Richard E.; Rossan, Richard N.

1981-01-01

174

Antifungal and antioxidant activities of the phytomedicine pipsissewa, Chimaphila umbellata.  

PubMed

Bioassay-guided fractionation of Chimaphila umbellata (L.) W. Bart (Pyrolaceae) ethanol extracts led to the identification of 2,7-dimethyl-1,4-naphthoquinone (chimaphilin) as the principal antifungal component. The structure of chimaphilin was confirmed by 1H and 13C NMR spectroscopy. The antifungal activity of chimaphilin was evaluated using the microdilution method with Saccharomyces cerevisiae (0.05mg/mL) and the dandruff-associated fungi Malassezia globosa (0.39mg/mL) and Malassezia restricta (0.55mg/mL). Pronounced antioxidant activity of C. umbellata crude extract was also identified using the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, suggesting this phytomedicine has an antioxidant function in wound healing. A chemical-genetic profile was completed with chimaphilin using approximately 4700 S. cerevisiae gene deletion mutants. Cellular roles of deleted genes in the most susceptible mutants and secondary assays indicate that the targets for chimaphilin include pathways involved in cell wall biogenesis and transcription. PMID:17950387

Galván, Imelda J; Mir-Rashed, Nadereh; Jessulat, Matthew; Atanya, Monica; Golshani, Ashkan; Durst, Tony; Petit, Philippe; Amiguet, Virginie Treyvaud; Boekhout, Teun; Summerbell, Richard; Cruz, Isabel; Arnason, John T; Smith, Myron L

2008-02-01

175

Environmental photochemistry on semiconductor surfaces: Photosensitized degradation of a textile azo dye, Acid Orange 7, on TiO{sub 2} particles using visible light  

SciTech Connect

Photosensitized degradation of a textile azo dye, Acid Orange 7, has been carried out on TiO{sub 2} particles using visible light. Mechanistic details of the dye degradation have been elucidated using diffuse reflectance absorption and FTIR techniques. Degradation does not occur on Al{sub 2}O{sub 3} surface or in the absence of oxygen. The dependence of the dye degradation rate on the surface coverage shows the participation of excited dye and TiO{sub 2} semiconductor in the surface photochemical process. Diffuse reflectance laser flash photolysis confirms the charge injection from the excited dye molecule into the conduction band of the semiconductor as the primary mechanism for producing oxidized dye radical. The surface-adsorbed oxygen plays an important role in scavenging photogenerated electrons, thus preventing the recombination between the oxidized dye radical and the photoinjected electrons. Diffuse reflectance FTIR was used to make a tentative identification of reaction intermediates and end products of dye degradation. The intermediates, 1,2-naphthoquinone and phthalic acid, have been identified during the course of degradation. Though less explored in photocatalysis, the photosensitization approach could be an excellent choice for the degradation of colored pollutants using visible light. 51 refs., 10 figs.

Vinodgopal, K.; Wynkoop, D.E. [Indiana Univ. Northwest, Gary, IN (United States)] [Indiana Univ. Northwest, Gary, IN (United States); Kamat, P.V. [Univ. of Notre Dame, IN (United States)] [Univ. of Notre Dame, IN (United States)

1996-05-01

176

Straightforward palladium-mediated synthesis and biological evaluation of benzo[j]phenanthridine-7,12-diones as anti-tuberculosis agents.  

PubMed

In 1991, WHO recognized the resurgence of tuberculosis as a global health problem. Although modern chemotherapy is effective against the causative pathogen Mycobacterium tuberculosis, the current drug regimens have failed to eradicate the disease. The success of the pathogen, partially attributed to drug resistance, necessitates the development of novel anti-tuberculosis drugs. Benzo[j]phenanthridine-7,12-diones, tetracyclic derivatives of the natural product benz[g]isoquinoline-5,10-dione, were conveniently synthesized via palladium-catalyzed intramolecular cyclization of N-methanesulfonyl-3-bromo-2-(arylamino)methyl-1,4-naphthoquinones. Here we report on the bioactivity of eight benzo[j]phenanthridine-7,12-dione derivatives as candidate drug molecules against M. tuberculosis and on their cytotoxicity on C3A human hepatocytes. The strongest antimicrobial activity (as detected by growth inhibition of bacteria, using luminometry and BACTEC 460-TB) and lowest cytotoxicity was found for 3-methylbenzo[j]phenanthridine-7,12-dione 5e, which was also effective in targeting intracellular M. tuberculosis (in murine J774 macrophages) and was not genotoxic for C3A hepatocytes. PMID:22182928

Cappoen, Davie; Jacobs, Jan; Nguyen Van, Tuyen; Claessens, Sven; Diels, Gaston; Anthonissen, Roel; Einarsdottir, Thorbjorg; Fauville, Maryse; Verschaeve, Luc; Huygen, Kris; De Kimpe, Norbert

2012-02-01

177

Main constituents of a commercial Drosera fluid extract and their antagonist activity at muscarinic M3 receptors in guinea-pig ileum.  

PubMed

The range of known constituents of Drosera species is extended by identification of myricetin 3-O-galactoside, from D. madagascariensis, and (+)-cis-isoshinanolone, obtained from a commercial fluid extract. They are accompanied by the naphthoquinones droserone and plumbagin, typical of this taxon, and a series of ubiquitous flavonols, including the rarely found gossypitrin present in the latter source. Conspicuously, the commercial form of D. peltata, non-accepted by the commission E, was found to be devoid of flavonoids. In addition, the fortuitous availability of the authentic enigmatic sample 'CON', previously isolated from D. rotundifolia, led to its characterization as common quercetin. Experiments performed on isolated guinea-pig ileum demonstrated that quercetin respectively 'CON' moderately inhibited carbachol-induced contractions at 10 microM (pD'2 5.09 +/- 0.02), while (+)-cis-isoshinanolone (100 microM) was inactive. This result indicates that quercetin derivatives may well contribute to the therapeutic use of Drosera preparations. PMID:11933852

Kolodziej, H; Pertz, H H; Humke, A

2002-03-01

178

Immobilized redox mediators on anion exchange resins and their role on the reductive decolorization of azo dyes.  

PubMed

Quinoid redox mediators (RM), including 1,2-naphthoquinone-4-sulfonate (NQS) and anthraquinone-2,6-disulfonate (AQDS), were adsorbed on anion exchange resins (AER) in order to explore their catalytic effects on the reductive decolorization of azo dyes by anaerobic granular sludge. Immobilized quinones preserved their catalytic properties once adsorbed on the surface of AER. Addition of different concentrations of immobilized quinones to sludge incubations increased up to 8.8-fold the rate of decolorization of azo dyes compared to controls lacking quinones. The catalytic effects of immobilized quinones also resulted in a greater extent of decolorization in quinone-amended incubations compared to controls lacking external RM. Spectrophotometric screening did not show any detachment of either AQDS or NQS during decolorization assays confirming that the enhanced decolorization accomplished was exclusively attributed to quinones immobilized on AER. Sterile controls including the maximum concentration of immobilized quinones supplied (4.8 mM) did not show any removal of azo dyes suggesting that physical-chemical processes, such as adsorption or chemical reduction, were not responsible for the enhanced decolorization reached. To our knowledge, this is the first study demonstrating the catalytic contribution of RM immobilized on AER on the reductive (bio)transformation of azo dyes. PMID:20136089

Cervantes, Francisco J; Garcia-Espinosa, Alberto; Moreno-Reynosa, M Antonieta; Rangel-Mendez, J Rene

2010-03-01

179

A quantitative high-throughput in vitro splicing assay identifies inhibitors of spliceosome catalysis.  

PubMed

Despite intensive research, there are very few reagents with which to modulate and dissect the mRNA splicing pathway. Here, we describe a novel approach to identify such tools, based on detection of the exon junction complex (EJC), a unique molecular signature that splicing leaves on mRNAs. We developed a high-throughput, splicing-dependent EJC immunoprecipitation (EJIPT) assay to quantitate mRNAs spliced from biotin-tagged pre-mRNAs in cell extracts, using antibodies to EJC components Y14 and eukaryotic translation initiation factor 4aIII (eIF4AIII). Deploying EJIPT we performed high-throughput screening (HTS) in conjunction with secondary assays to identify splicing inhibitors. We describe the identification of 1,4-naphthoquinones and 1,4-heterocyclic quinones with known anticancer activity as potent and selective splicing inhibitors. Interestingly, and unlike previously described small molecules, most of which target early steps, our inhibitors represented by the benzothiazole-4,7-dione, BN82685, block the second of two trans-esterification reactions in splicing, preventing the release of intron lariat and ligation of exons. We show that BN82685 inhibits activated spliceosomes' elaborate structural rearrangements that are required for second-step catalysis, allowing definition of spliceosomes stalled in midcatalysis. EJIPT provides a platform for characterization and discovery of splicing and EJC modulators. PMID:22252314

Berg, Michael G; Wan, Lili; Younis, Ihab; Diem, Michael D; Soo, Michael; Wang, Congli; Dreyfuss, Gideon

2012-04-01

180

A novel liquid chromatography-tandem mass spectrometry method for determination of menadione in human plasma after derivatization with 3-mercaptopropionic acid.  

PubMed

Menadione (VK3), an essential fat-soluble naphthoquinone, takes very important physiological and pathological roles, but its detection and quantification is challenging. Herein, a new method was developed for quantification of VK3 in human plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after derivatization with 3-mercaptopropionic acid via Michael addition reaction. The derivative had been identified by the mass spectra and the derivatization conditions were optimized by considering different parameters. The method was demonstrated with high sensitivity and a low limit of quantification of 0.03 ng mL(-1) for VK3, which is about 33-fold better than that for the direct analysis of the underivatized compound. The method also had good precision and reproducibility. It was applied in the determination of basal VK3 in human plasma and a clinical pharmacokinetic study of menadiol sodium diphosphate. Furthermore, the method for the quantification of VK3 using LC-MS/MS was reported in this paper for the first time, and it will provide an important strategy for the further research on VK3 and menadione analogs. PMID:25059129

Liu, Ruijuan; Wang, Mengmeng; Ding, Li

2014-10-01

181

Detection of relative [Na+] and [K+] levels in sweat with optical measurements  

NASA Astrophysics Data System (ADS)

We describe the use of 2-hydroxy-1,4-naphthoquinone (HNQ, Lawsone) as a potential sweat electrolyte measurement marker. We use ultraviolet-visible absorbance measurements to determine the absorbance energy in a particular wavelength range (400 nm-500 nm). This novel approach allows us to eliminate the importance of the exact wavelength of the absorbance peak but find the integral of the range of interest. Although we numerically calculate the absorbance energy, it is imperative to use photodiodes to measure the intensity of the transmitted light that is fabricated particularly for the range of interest for future device implementations. We explored various mixing ratios of water and acetone to find the optimum solvent that would give the most sensitive and accurate relative electrolyte sensing. The pH value was also modified to see the effect on the absorbance energy and intensity. A representative group of subjects were used to collect sweat from the dehydration and hyperhydration cases. The results are convincing that HNQ solutions can be used as a wearable, continuous sweat sensor.

Al-omari, Mahmoud; Sel, Kivanc; Mueller, Anja; Edwards, Jeffery; Kaya, Tolga

2014-05-01

182

Tyrosinase inhibitors from Calceolaria integrifolia s.l.: Calceolaria talcana aerial parts.  

PubMed

As a defense mechanism of the aerial parts of Calceolaria talcana (Calceolariaceae; formerly Scrophulariaceae) against herbivore offenses and insect pest attack, diterpenoids, triterpenoids, phenylethanoids, flavonoids, and iridoids are rapidly accumulated along the aerial parts, resulting in a unique natural biopesticide complex from this plant. In addition to verbascoside a series of known compounds were screened for their inhibitory activity against mushroom tyrosinase and protease enzymes. Ethyl acetate and n-hexane extracts, together with cyclopropyl-7,15-ent-pimaradiene (1), abietatriene (2), ursolic acid (3), ?-lupeol (4), ?-sitosterol (5), 2-hydroxy-3-(1,1-dimethylallyl)-1,4-naphthoquinone (6), ?-dunnione (7), verbascoside (8), martynoside (9), and some known model compounds proved to be inhibitors of oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosinase (EC 1.14.18.1) with an IC50 between 10.0 and 200 ppm or ?M, respectively, suggesting that phenolic moieties in the molecules assayed are important for the activity. PMID:23607420

Muñoz, Evelyn; Avila, Jose G; Alarcón, Julio; Kubo, Isao; Werner, Enrique; Céspedes, Carlos L

2013-05-01

183

Bioassay-guided isolation of anti-inflammatory and antinociceptive compound from Plumbago zeylanica leaf.  

PubMed

Plumbago zeylanica Linn. (Plumbaginaceae) is used in the treatment of various inflammatory ailments in traditional medicines. In order to validate these ethnobotanical practices, the anti-inflammatory and antinociceptive activities of various leaf extracts (petroleum ether (60-80 degrees ), chloroform, acetone, ethanol, and aqueous) were studied using in vivo experimental models at two dose levels (200 and 400 mg/kg, p.o.). Anti-inflammatory activity was tested using the carrageenan induced rat hind paw edema method while analgesic activity was studied using the hot plate and formalin induced models. Diclofenac (100 mg/ kg) was used as the reference standard in both anti-inflammatory and analgesic models and morphine (10 mg/ kg, i.p.) was used as the reference standard in the formalin induced analgesic model. The acetone extract significantly (p < 0.01) reduced inflammation in the rats when compared to the control group. As for the analgesia effect, the acetone and petroleum ether extracts significantly (p < 0.01) decreased the pain stimulus only in the later phase of the formalin test, suggesting that the drug could be peripherally acting. Bioassay-guided fractionation of the acetone extract led to the isolation and identification of plumbagin. Structure elucidation of plumbagin confirmed it as 5-hydroxy-2-methyl-1,4-naphthoquinone, a naphthaquinone derivative, through spectral techniques. PMID:20645715

Sheeja, E; Joshi, S B; Jain, D C

2010-04-01

184

Determination and identification of plumbagin from the roots of Plumbago zeylanica L. by liquid chromatography with tandem mass spectrometry.  

PubMed

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is an herbal ingredient which is isolated from the root of Plumbago zeylanica L. This herb is a semi-climbing subshrub distributed in thickets or grassland at low elevations of Taiwan. The crushed roots of P. zeylanica L. were ground from lumps to powder and boiled with H2O, 50% EtOH, or 95% EtOH. Chromatographic separation of plumbagin from the herb was carried out using a ZORBAX Extend-C18 column (150 x 4.6 mm I.D.; 5 microm) that was eluted with the mobile phase of water-methanol (10:90, v/v). Multiple reaction monitoring (MRM) was used to monitor the transition of the deprotonated molecule m/z 187 [M-H]- to the product ion m/z 159 [M-H-CO]- for plumbagin analysis. The limit of quantification was determined to and accuracy of 1 ng/ml. Furthermore, the mass fractions of plumbagin in P. zeylanica L. for H2O, 50% EtOH and 95% EtOH were 0.24 +/- 0.04, 3.92 +/- 0.87 and 13.4 +/- 1.59 g/kg, respectively. These results present a reliable liquid chromatography coupled with tandem mass spectrometric (LC-MS/MS) method for the determination of plumbagin form herbal medicines. PMID:16078700

Hsieh, Yen-Ju; Lin, Lei-Chwen; Tsai, Tung-Hu

2005-08-12

185

Direct protective effect of NAD(P)H:quinone reductase against menadione-induced chemiluminescence of postmitochondrial fractions of mouse liver.  

PubMed

In the presence of NADPH and oxygen, menadione (2-methyl-1,4-naphthoquinone) elicits low level red chemiluminescence from rodent liver preparations. This chemiluminescence is believed to arise from the formation of active oxygen species that are generated when the quinone undergoes oxidative cycling. The obligatory two-electron reduction of quinones to hydroquinones catalyzed by NAD(P)H:(quinone-acceptor) oxidoreductase (EC 1.6.99.2) has been implicated in the suppression of this photoemission by competing with oxidative cycling (Wefers, H., Komai, T., Talalay, P., and Sies, H. (1984) FEBS Lett. 169, 63-66 and references therein). Thus, in previous studies, we showed that treatment of mice with BHA (2(3)-tert-butyl-4-hydroxyanisole), which elevates cytosolic quinone reductase activity about 10-fold, reduced menadione-dependent chemiluminescence of hepatic post-mitochondrial supernatant fractions, whereas inhibition of quinone reductase by dicoumarol greatly intensified light emission. We demonstrate here that addition of pure quinone reductase to this preparation suppresses menadione-dependent chemiluminescence, and that the protective effect of 2(3)-tert-butyl-4-hydroxyanisole treatment can be accounted for completely by the induction of this specific enzyme. These results provide conclusive evidence that in this system the protective action of anticarcinogenic antioxidants is entirely attributable to the elevation of the level of an electrophile-processing enzyme. PMID:2434474

Prochaska, H J; Talalay, P; Sies, H

1987-02-15

186

A Quantitative High-Throughput In Vitro Splicing Assay Identifies Inhibitors of Spliceosome Catalysis  

PubMed Central

Despite intensive research, there are very few reagents with which to modulate and dissect the mRNA splicing pathway. Here, we describe a novel approach to identify such tools, based on detection of the exon junction complex (EJC), a unique molecular signature that splicing leaves on mRNAs. We developed a high-throughput, splicing-dependent EJC immunoprecipitation (EJIPT) assay to quantitate mRNAs spliced from biotin-tagged pre-mRNAs in cell extracts, using antibodies to EJC components Y14 and eukaryotic translation initiation factor 4aIII (eIF4AIII). Deploying EJIPT we performed high-throughput screening (HTS) in conjunction with secondary assays to identify splicing inhibitors. We describe the identification of 1,4-naphthoquinones and 1,4-heterocyclic quinones with known anticancer activity as potent and selective splicing inhibitors. Interestingly, and unlike previously described small molecules, most of which target early steps, our inhibitors represented by the benzothiazole-4,7-dione, BN82685, block the second of two trans-esterification reactions in splicing, preventing the release of intron lariat and ligation of exons. We show that BN82685 inhibits activated spliceosomes' elaborate structural rearrangements that are required for second-step catalysis, allowing definition of spliceosomes stalled in midcatalysis. EJIPT provides a platform for characterization and discovery of splicing and EJC modulators. PMID:22252314

Berg, Michael G.; Wan, Lili; Younis, Ihab; Diem, Michael D.; Soo, Michael; Wang, Congli

2012-01-01

187

Combining microdilution with MicroResp™: microbial substrate utilization, antimicrobial susceptibility and respiration.  

PubMed

Pharmacological studies focus on susceptibility of pathogenic microbes against specific drugs or combinations of them, ecological studies on substrate utilization efficiency of variable microbial communities. The MicroResp™ system was especially developed to study soil microbial communities. It was slightly modified to facilitate exploring of microbial growth efficiency in a concentration-dependent fashion (microdilutions of carbohydrate mixtures or specific toxic chemicals). After turbidimetric growth assessment, colorimetric indicator plates (cresol red agar) were mounted to the assay plates. The substrate utilisation design is illustrated by glucose and a plant carbohydrate mixture, the antimicrobial susceptibility design by the naphthoquinone juglone. Dose-response effects are explored by curve fitting of nonlinear models that especially have been developed to detect hormetic effects that are characterized by stimulation at lower followed by inhibition at higher dosages (U- and inverse U-shaped effects). Multivariate analyses are presented utilizing metavariables that were obtained in the curve fitting process of the measured parameters growth and respiration and the factor growth efficiency. PMID:22265657

Drage, Sigrid; Engelmeier, Doris; Bachmann, Gert; Sessitsch, Angela; Mitter, Birgit; Hadacek, Franz

2012-03-01

188

Molecular Structure of Urushiol  

NSDL National Science Digital Library

Urushiol is a yellow oil comprised of a mixture of organic compounds containing a catechol (1,2-hydroxy benzene) and a pentadecyl or heptadecyl side chain; some side chains may be unsaturated. The earliest use of urushiol was in the art of ancient Asia, where works of art were coated in lacquer finishes derived from the trees Toxicodendron vernicifluum or Rhus verniciflua. In fact, the name urushiol is derived from urushi, the Japanese word for the lacquer prepared from the sap of the Japanese lacquer tree ("kiurushi"). During the lacquering process, the phenols oxidize and polymerize with the help of enzymes to yield a coating that is hard and resistant to mechanical stress. Inhabitants of North America are familiar with the more malevolent side of urushiol-as the active ingredient of poison ivy and poison oak. Most people are highly allergic to urushiol and will develop redness, painful itching, and blistering of the skin if they touch even minute amounts of the oil. Interestingly, one of the most effective remedies for poison ivy comes also from a plant. The Jewelweed plant (Impatiens capensis) found in North American hardwood forests produces a chemical called Lawsone (a naphthoquinone) with antihistamine and anti-inflammatory properties that lessen the effects of urushiol on the skin.

2006-04-19

189

Evaluation of radical scavenging properties of shikonin  

PubMed Central

With the aim of developing effective anti-inflammatory drugs, we have been investigating the biochemical effects of shikonin of “Shikon” roots, which is a naphthoquinone with anti-inflammatory and antioxidative properties. Shikonin scavenged reactive oxygen species like hydroxyl radical, superoxide anion (O2•?) and singlet oxygen in previous studies, but its reactivity with reactive oxygen species is not completely understood, and comparison with standard antioxidants is lacking. This study aimed elucidation of the reactivity of shikonin with nitric oxide radical and reactive oxygen species such as alkyl-oxy radical and O2•?. By using electron paramagnetic resonance spectrometry, shikonin was found unable of reacting with nitric oxide radical in a competition assay with oxyhemoglobin. However, shikonin scavenged alkyl-oxy radical from 2,2'-azobis(2-aminopropane) dihydrochloride with oxygen radical absorbance capacity, ORAC of 0.25 relative to Trolox, and showed a strong O2•?-scavenging ability (42-fold of Trolox; estimated reaction rate constant: 1.7 × 105 M?1s?1) in electron paramagnetic resonance assays with CYPMPO as spin trap. Concerning another source of O2•?, the phagocyte NADPH oxidase (Nox2), shikonin inhibited the Nox2 activity by impairing catalysis when added before enzyme activation (IC50: 1.1 µM; NADPH oxidation assay). However, shikonin did not affect the preactivated Nox2 activity, although having potential to scavenge produced O2•?. In conclusion, shikonin scavenged O2•? and alkyl-oxy radical, but not nitric oxide radical.

Yoshida, Lucia S.; Kohri, Shunji; Tsunawaki, Shohko; Kakegawa, Tomohito; Taniguchi, Taizo; Takano-Ohmuro, Hiromi; Fujii, Hirotada

2014-01-01

190

In vitro evaluation of the growth inhibitory activities of 15 drugs against Babesia gibsoni (Aomori strain).  

PubMed

The in vitro growth inhibitory activities of 15 drugs against Babesia gibsoni were evaluated following establishment of a continuous culture isolate (Aomori isolate). The culture was successfully continued in an RPMI-1640 medium supplemented with 20% normal canine serum or fetal bovine serum in a humidified atmosphere containing 5% CO2 and 5% O2 at 37 degrees C. We used this isolate to evaluate the growth inhibitory effect of naphthoquinone (atovaquone), aromatic diamidine (diminazene and pentamidine), artemisinin compounds (artesunate and dihydroartemisinin), an iron chelator (deferoxamine), quinoline-containing compounds (quinine and chloroquine), macrolide antibiotics (azithromycin), lyncomycin antibiotics (clindamycin), tetracycline antibiotics (doxycycline and minocycline), imidazole antifungals (clotrimazole and ketoconazole), and a nitroimidazole antiprotozoal (metronidazole). Atovaquone and aromatic diamidine showed the highest activity; they were followed by artesunate compounds with nanomole levels of IC50. Metronidazole did not exhibit activity against the parasite. Other drugs exhibited intermediate in vitro activities with micromole levels of IC50. This is the first report to screen drug activities against B. gibsoni in vitro. The results of our study may support further in vitro drug evaluation for the establishment of therapeutic strategies against canine B. gibsoni infections. PMID:18771856

Matsuu, Aya; Yamasaki, Masahiro; Xuan, Xuenan; Ikadai, Hiromi; Hikasa, Yoshiaki

2008-10-20

191

Determination of the degradation products of selected sulfonated phenylazonaphthol dyes treated by white rot fungus Pleurotus ostreatus by capillary electrophoresis coupled with electrospray ionization ion trap mass spectrometry.  

PubMed

The removal of water-soluble sulphonated phenylazonaphthol dye effluents generated by textile industries is an important issue in wastewater treatment. Microbial treatment of environmental pollutants including dyes, with white rot fungi has received wide attention as a potential alternative for conventional methods in wastewater treatment. Three sulphonated phenylazonaphthol dyes with similar molecular structures Acid Orange 7, Acid Orange 8 and Mordant Violet 5 were selected and degraded by the white rot fungus Pleurotus ostreatus. Chemical instrumental analysis methods such as high-performance liquid chromatography (HPLC) and capillary electrophoresis combined with electrospray ionization mass spectrometry (CE-ESI-MS) were used to identify the degraded dyes. Mordant Violet 5 had two degradation pathways when degraded by P. ostreatus. The first degradation pathway for Mordant Violet 5 was for trans structure and the cis-Mordant Violet 5 followed the second pathway. Acid Orange 8 and Acid Orange 7 had the same degradation mechanism as the first degradation mechanism for Mordant Violet 5, that is cleavage of azo bond at the naphthalene ring side where benzenesulfonic acid and 1,2-naphthoquinone are formed. PMID:18778834

Lu, Yiping; Phillips, Dennis R; Lu, Lude; Hardin, Ian R

2008-10-24

192

Dihydrodiol dehydrogenase and polycyclic aromatic hydrocarbon metabolism  

SciTech Connect

Carcinogenic activation of polycyclic aromatic hydrocarbons by microsomal monoxygenases proceeds through trans-dihydrodiol metabolites to diol-epoxide ultimate carcinogens. This thesis directly investigated the role of dihydrodiol dehydrogenase, a cytosolic NAD(P)-linked oxidoreductase, in the detoxification of polycyclic aromatic trans-dihydrodiols. A wide variety of non-K-region trans-dihydrodiols were synthesized and shown to be substrates for the homogeneous rat liver dehydrogenase, including several potent proximate carcinogens derived from 7,12-dimethylbenz(a)anthracene, 5-methylchrysene, and benzo(a)pyrene. Since microsomal activation of polycyclic aromatic hydrocarbons is highly stereospecific, the stereochemical course of enzymatic trans-dihydrodiol oxidation was monitored using circular dichroism spectropolarimetry. The major product formed from the dehydrogenase-catalyzed oxidation of the trans-1,2-dihydrodiol of naphthalene was characterized using UV, IR, NMR, and mass spectroscopy, and appears to be 4-hydroxy-1,2-naphthoquinone. Mass spectral analysis suggests that an analogous hydroxylated o-quinone is formed as the major product of benzo(a)pyrene-7,8-dihydrodiol oxidation. Enzymatic oxidation of trans-dihydrodiols was shown to be potently inhibited by all of the major classes of the nonsteroidal antiinflammatory drugs. Enhancement of trans-dihydrodiol proximate carcinogen oxidation may protect against possible adverse effects of the aspirin-like drugs, and help maintain the balance between activation and detoxification of polycyclic aromatic hydrocarbons.

Smithgall, T.E.

1986-01-01

193

Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey.  

PubMed

Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent Km, Vmax, and catalytic efficiency (Vmax/Km) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar Km and Vmax appeared to metabolize naphthalene. The rank order of Vmax (rat olfactory epithelium>mouse olfactory epithelium>murine airways>rat airways) correlated well with tissue susceptibility to naphthalene. The Vmax in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. PMID:23602890

Buckpitt, Alan; Morin, Dexter; Murphy, Shannon; Edwards, Patricia; Van Winkle, Laura

2013-07-15

194

Structural organization of a Bacillus subtilis operon encoding menaquinone biosynthetic enzymes.  

PubMed

Menaquinone (MK) is a non-protein component of the Bacillus subtilis (Bs) electron transport chain synthesized from chorismate through a series of MK-specific reactions. The genes encoding biosynthesis of the naphthoquinone ring of MK are clustered at 273 degrees on the Bs chromosome. A 3.9-kb region capable of rescuing men mutants blocked in the early stages of MK biosynthesis was sequenced and found to contain three major open reading frames (ORFs). The first ORF (menF) has a predicted size of 51.8 kDa and 34% amino-acid identity with the isochorismate synthases of Escherichia coli (EntC) and Aeromonas hydrophila (AmoA), ORF2 (menD) a predicted size of 60.2 kDa and 21% identity with MenD of E. coli. ORF3 has a predicted size of 21.4 kDa and 29% identity to triacylglycerol lipase of Psychrobacter immobilis. No sequence corresponding to menC was identified. Plasmid integrational studies of the men gene cluster had suggested the presence of promoters secondary to the previously identified p1 men promoter. Sequence analysis revealed a putative promoter region upstream from ORF3. PMID:8566759

Rowland, B; Hill, K; Miller, P; Driscoll, J; Taber, H

1995-12-29

195

Identification of a Molecular Activator for Insulin Receptor with Potent Anti-diabetic Effects*  

PubMed Central

Insulin exerts its actions through the insulin receptor (IR) and plays an essential role in diabetes. The inconvenient daily injection and undesirable side-effects associated with insulin injection demand novel drugs for the diseases. To search for bioactive insulin mimetics, we developed an in vitro screening assay using phospho-IR ELISA. After screening the small molecule chemical libraries, we have obtained a compound (5,8-diacetyloxy-2,3-dichloro-1,4-naphthoquinone) that provokes IR activation by directly binding to the receptor kinase domain to trigger its kinase activity at micromolar concentrations. This compound selectively activates IR but not other receptors and sensitizes insulin's action. Moreover, it elevates glucose uptake in adipocytes and has oral hypoglycemic effect in wild-type C57BL/6J mice and db/db and ob/ob mice without demonstrable toxicity. Hence, this promising compound mimics the biological functions of insulin and is useful for further drug development for diabetes treatment. PMID:21908618

He, Kunyan; Chan, Chi-Bun; Liu, Xia; Jia, Yonghui; Luo, Hongbo R.; France, Stefan A.; Liu, Yang; Wilson, W. David; Ye, Keqiang

2011-01-01

196

2-Phenylaminonaphthoquinones and related compounds: Synthesis, trypanocidal and cytotoxic activities.  

PubMed

A series of new 2-aminonaphthoquinones and related compounds were synthesized and evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity and selectivity as compared with current trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than nifurtimox against Trypanosoma cruzi in comparison with Vero cells. Some of the synthesized quinones were tested against cancer cells and normal fibroblasts, showing that certain chemical modifications on the naphthoquinone moiety induce and excellent increase the selectivity index of the cytotoxicity (4g and 10). The results presented here show that the anti-T. cruzi activity of 2-aminonaphthoquinones derivatives can be improved by the replacement of the benzene ring by a pyridine moiety. Interestingly, the presence of a chlorine atom at C-3 and a highly lipophilic alkyl group or aromatic ring are newly observed elements that should lead to the discovery of more selective cytotoxic and trypanocidal compounds. PMID:25127463

Sieveking, Ivan; Thomas, Pablo; Estévez, Juan C; Quiñones, Natalia; Cuéllar, Mauricio A; Villena, Juan; Espinosa-Bustos, Christian; Fierro, Angélica; Tapia, Ricardo A; Maya, Juan D; López-Muñoz, Rodrigo; Cassels, Bruce K; Estévez, Ramon J; Salas, Cristian O

2014-09-01

197

Synthesis and molecular structure of a zinc complex of the vitamin K3 analogue phthiocol  

NASA Astrophysics Data System (ADS)

The complex [Zn(phthiocol)2(H2O)2]; 1, where phthiocol is 2-hydroxy-3-methyl-1,4-naphthoquinone, has been synthesized and characterized by elemental analysis, FT-IR, 1H NMR, UV-vis spectroscopy, thermogravimetric (TG) analysis, electrochemical and single crystal X-ray diffraction studies. The ?CO stretch shifts to lower frequencies upon complexation of phthiocol to Zn2+. 1H NMR spectra show an upfield shift of the benzenoid ring protons in 1. There is a bathochromic shift of the LMCT band in the UV-vis spectra of 1. Single crystal X-ray structure of 1 show distorted octahedral geometry around Zn2+. Two phthiocol ligands are in plane with the metal, while water molecules are trans to this plane. Coordination of deprotonated phthiocol ligands is 'trans, trans' to Zn2+. Intra as well as intermolecular interactions are observed in 1. Molecules of 1 show three dimensional network through CH⋯O and OH⋯O interactions. Additional anodic peaks are observed in cyclic voltammogram of phthiocol ligand due to oxidation of reduced species formed during reduction. One-electron reduction of 1 is shown to be reversible and DFT studies define this redox event as ligand-centered.

Kathawate, Laxmi; Sproules, Stephen; Pawar, Omkar; Markad, Ganesh; Haram, Santosh; Puranik, Vedavati; Salunke-Gawali, Sunita

2013-09-01

198

The anatomy and chemistry of the colour bands of grasstree stems (Xanthorrhoea preissii) used for plant age and fire history determination.  

PubMed

A new method of ageing and determining the fire history of grasstrees, based on colour bands running along the stem, has been developed. As part of our evaluation of the technique, we examined the structural and chemical basis of the colour differences. Exposed ends of the leaf bases are cream, brown and black, with the inner cortex, especially in the black leaf bases, being darker than the outer cortex. There was no structural difference between the three leaf base types. Tannin concentration increased from cream to brown to black leaf bases, and from the inner to outer cortex, and remained quite stable over many years. Both water-soluble and insoluble pigments contribute to the darkness of the black leaf bases. A hydrophobic naphthoquinone was present in the conducting tissues of the vascular bundles, and related naphthalene-derivatives were present in the surrounding tissues. We conclude that the colour differences between the leaf bases have a chemical basis that can be linked to environmental changes: tannin cells to phenological effects, and naphthalene-derivatives in the vascular core to the passage of fire. PMID:12099535

Colangelo, Wendy I; Lamont, Byron B; Jones, Anthea S; Ward, David J; Bombardieri, Sandro

2002-05-01

199

The Anatomy and Chemistry of the Colour Bands of Grasstree Stems (Xanthorrhoea preissii) used for Plant Age and Fire History Determination  

PubMed Central

A new method of ageing and determining the fire history of grasstrees, based on colour bands running along the stem, has been developed. As part of our evaluation of the technique, we examined the structural and chemical basis of the colour differences. Exposed ends of the leaf bases are cream, brown and black, with the inner cortex, especially in the black leaf bases, being darker than the outer cortex. There was no structural difference between the three leaf base types. Tannin concentration increased from cream to brown to black leaf bases, and from the inner to outer cortex, and remained quite stable over many years. Both water?soluble and insoluble pigments contribute to the darkness of the black leaf bases. A hydrophobic naphthoquinone was present in the conducting tissues of the vascular bundles, and related naphthalene?derivatives were present in the surrounding tissues. We conclude that the colour differences between the leaf bases have a chemical basis that can be linked to environmental changes: tannin cells to phenological effects, and naphthalene?derivatives in the vascular core to the passage of fire. PMID:12099535

COLANGELO, WENDY I.; LAMONT, BYRON B.; JONES, ANTHEA S.; WARD, DAVID J.; BOMBARDIERI, SANDRO

2002-01-01

200

Cytotoxicity and In Vitro Antileishmanial Activity of Antimony (V), Bismuth (V), and Tin (IV) Complexes of Lapachol  

PubMed Central

Leishmania amazonensis is the etiologic agent of the cutaneous and diffuse leishmaniasis often associated with drug resistance. Lapachol [2-hydroxy-3-(3?-methyl-2-butenyl)-1,4-naphthoquinone] displays a wide range of antimicrobial properties against many pathogens. In this study, using the classic microscopic in vitro model, we have analyzed the effects of a series of lapachol and chlorides complexes with antimony (V), bismuth (V), and tin (IV) against L. amazonensis. All seven compounds exhibited antileishmanial activity, but most of the antimony (V) and bismuth (V) complexes were toxic against human HepG2 cells and murine macrophages. The best IC50 values (0.17 ± 0.03 and 0.10 ± 0.11??g/mL) were observed for Tin (IV) complexes (3) [(Lp)(Ph3Sn)] and (6) (Ph3SnCl2), respectively. Their selective indexes (SIs) were 70.65 and 120.35 for HepG2 cells, respectively. However, while analyzing murine macrophages, the SI decreased. Those compounds were moderately toxic for HepG2 cells and toxic for murine macrophages, still underlying the need of chemical modification in this class of compounds. PMID:23781165

Rocha, Marcele Neves; Nogueira, Paula Monalisa; Demicheli, Cynthia; de Oliveira, Ludmila Gonçalvez; da Silva, Meiriane Mariano; Frézard, Frédéric; Melo, Maria Norma; Soares, Rodrigo Pedro

2013-01-01

201

Effect of nitrogen source on end products of naphthalene degradation  

SciTech Connect

Soil cultures, enrichment cultures, and pure culture isolates produced substantial quantities of salicylic acid from naphthalene in a mineral salts medium containing NH/sub 4/Cl as the nitrogen source. However, when KNO/sub 3/ was substituted for NH/sub 4/Cl, these same cultures failed to accumulate detectable quantities of salicylic acid but did not turn the medium yellow. When an isolate identified as a Pseudomonas species was used, viable cell numbers were much greater in the medium containing KNO/sub 3/ but up to 94% of the naphthalene was utilized in both media. The differences between nitrogen sources could not be accounted for by pH alone since results obtained using buffered media were similar. Growth with NH/sub 4/NO/sub 3/ displayed a pattern similar to that obtained when NH/sub 4/Cl was used. The yellow coloration in the medium containing KNO/sub 3/ was apparently due to more than one compound, none of which were 1,2-naphthoquinone or acidic in nature, as suggested by other investigators. Further attempts to identify the yellow compounds by high-pressure liquid chromatography, infrared analysis, and gas chromatography-mass spectrometry have been unsuccessful thus far.

Aranha, H.G.; Brown, L.R.

1981-07-01

202

Characterization of a rat NADPH-dependent aldo-keto reductase (AKR1B13) induced by oxidative stress.  

PubMed

A rat aldo-keto reductase (AKR1B13) was identified as a hepatoma-derived protein, exhibiting high sequence identity with mouse fibroblast growth factor (FGF)-induced reductase, AKR1B8. In this study, AKR1B13 was characterized in terms of its enzymatic properties, tissue distribution and regulation. Recombinant AKR1B13 exhibited NADPH-linked reductase activity towards various aldehydes and alpha-dicarbonyl compounds, which include reactive compounds such as methylglyoxal, glyoxal, acrolein, 4-hydroxynonenal and 3-deoxyglucosone. The enzyme exhibited low NADP(+)-linked dehydrogenase activity towards aliphatic and aromatic alcohols, and was inhibited by aldose reductase inhibitors, flavonoids, benzbromarone and hexestrol. Immunochemical and reverse transcription-PCR analyses revealed that the enzyme is expressed in many rat tissues, endothelial cells and fibroblasts. Gene expression in YPEN-1 and NRK cells was up-regulated by treatments with submicromolar concentrations of hydrogen peroxide and 1,4-naphthoquinone, but not with FGF-1, FGF-2, 5alpha-dihydrotestosterone and 17beta-estradiol. These results indicate that AKR1B13 differs from AKR1B8 in tissue distribution and gene regulation, and suggest that it functions as a defense system against oxidative stress in rat tissues. PMID:18845131

Endo, Satoshi; Matsunaga, Toshiyuki; Mamiya, Hiroaki; Hara, Akira; Kitade, Yukio; Tajima, Kazuo; El-Kabbani, Ossama

2009-03-16

203

Synthesis, Photochemical and Photoinduced Antibacterial Activity Studies of meso-Tetra(pyren-1-yl)porphyrin and its Ni, Cu and Zn Complexes  

PubMed Central

The synthesis of the meso-tetra(pyren-1-yl)porphyrin (1) was successfully accomplished by means of the pyrrole condensation with pyrene-1-carb-aldehyde in acidic media. Its metallization was carried out in an almost quantitative yield to obtain the corresponding complexes of Ni(II) (2), Cu(II) (3) and Zn (4). Their photophysical properties such as fluorescence quantum yield and energy transfer to oxygen for an efficient generation of singlet oxygen were determined. Their photophysical and photochemical properties were compared with those of other similar porphyrin derivatives such as tetraphenylporphyrin and tetranaphthylporphyrin. Photochemical studies on their effectiveness as photosensitizer were carried out by means of the photoinduced oxidation of aromatic alcohols like ?-naphthol to naphthoquinone. The antibacterial photoactivity assay for compounds 1–4 was testeted against Escherichia coli (ATCC 8739) and its proliferation and viability were measured by chemiluminescence. An efficient inactivation of E. coli was observed. This was more efficient for compounds 2 and 3, following the direct relationship to high generation of singlet oxygen by these compounds. PMID:21179316

Zoltan, Tamara; Vargas, Franklin; Rivas, Carlos; Lopez, Veronica; Perez, Jhackelym; Biasutto, Antonio

2010-01-01

204

Plumbagin suppresses dendritic cell functions and alleviates experimental autoimmune encephalomyelitis.  

PubMed

Plumbagin (PL, 5-hydroxy-2-methyl-1,4-naphthoquinone) is a herbal compound derived from medicinal plants of the Droseraceae, Plumbaginaceae, Dioncophyllaceae, and Ancistrocladaceae families. Reports have shown that PL exerts immunomodulatory activity and may be a novel drug candidate for immune-related disease therapy. However, its effects on dendritic cells (DCs), the most potent antigen-presenting cells (APCs), remain unclear. In this study, we demonstrate that PL inhibits the differentiation, maturation, and function of human monocyte-derived DCs. PL can also restrict the expression of Th1- and Th17-polarizing cytokines in mDC. In addition, PL suppresses DCs both in vitro and in vivo, as demonstrated by its effects on the mouse DC line DC2.4 and mice with experimental autoimmune encephalomyelitis (EAE), respectively. Notably, PL ameliorated the clinical symptoms of EAE, including central nervous system (CNS) inflammation and demyelination. Our results demonstrate the immune suppressive and anti-inflammatory properties of PL via its effects on DCs and suggest that PL could be a potential treatment for DC-related autoimmune and inflammatory diseases. PMID:24953531

Zhang, Kai; Ge, Zhenzhen; Da, Yurong; Wang, Dong; Liu, Ying; Xue, Zhenyi; Li, Yan; Li, Wen; Zhang, Lijuan; Wang, Huafeng; Zhang, Huan; Peng, Meiyu; Hao, Junwei; Yao, Zhi; Zhang, Rongxin

2014-08-15

205

Bioprocessing of lignite coals using reductive microorganisms  

SciTech Connect

A major goal of this project is to isolate unique microbial strains that catalyze a variety of biochemical transformations of low molecular weight coal substructure model compounds and then to determine if these strains will carry out similar reactions with coal. We have several enrichments underway using suitable model compounds such as pyrogallol (2,3-dihydroxyphenol) and gallic acid (3,4,5-trihydroxybenzoic acid) to isolate organisms that reductively dehydroxylate phenolic hydroxyl groups. We are also using various naphthoquinone and antrhaquinone dyes as substrates in isolation procedures. The most promising results so far are with hydroxynaphthoquinone. The purple non-sulfur bacteria belonging to the genus Rhodobacter are also of interest to us because some of them degrade numerous aromatic compounds by way of reductive pathways. In addition, Rhodobacter species are not sensitive to air. Thus far, enrichment cultures with benzoate have yielded two isolates. Lowering the carboxyl content of lignite coal has been suggested as one means of improving its fuel value. We have isolated a bacterium from soil, tentatively identified as a Bacillus species, that nonoxidatively decarboxylates vanillic acid to guaicol. This bacterium also decarboxylated p-hydroxycinnimates to p-hydroxystyrenes. We are now attempting to get measurable decarboxylation of base-solubilized Vermont lignite coal using this organism. 1 tab.

Crawford, D.L.

1989-01-01

206

Involvement of the cell-specific pigment genes pks and sult in bacterial defense response of sea urchins Strongylocentrotus intermedius.  

PubMed

Bacterial infections are one of the most important problems in mass aquaculture, causing the loss of millions of juvenile organisms. We isolated 22 bacterial strains from the cavity fluid of the sea urchin Strongylocentrotus pallidus and used phylogenetic analysis based on 16S rRNA gene sequences to separate the bacterial strains into 9 genera (Aliivibrio, Bizionia, Colwellia, Olleya, Paenibacillus, Photobacterium, Pseudoalteromonas, Shewanella, and Vibrio). Incubating Strongylocentrotus intermedius larvae with a strain from each of the 9 bacterial genera, we investigated the viability of the larvae, the amount of pigment cells, and the level of polyketide synthase (pks) and sulfotransferase (sult) gene expression. Results of the assay on sea urchin development showed that all bacterial strains, except Pseudoalteromonas and Bizionia, suppressed sea urchin development (resulting in retardation of the embryos' development with cellular disorders) and reduced cell viability. We found that pks expression in the sea urchin larvae after incubation with the bacteria of 9 tested genera was significantly increased, while the sult expression was increased only after the treatment with Pseudoalteromonas and Shewanella. Shikimic acid, which is known to activate the biosynthesis of naphthoquinone pigments, increased the tolerance of the sea urchin embryos to the bacteria. In conclusion, we show that the cell-specific pigment genes pks and sult are involved in the bacterial defense response of sea urchins. PMID:23548362

Kiselev, Konstantin V; Ageenko, Natalya V; Kurilenko, Valeria V

2013-03-26

207

Un nouveau film conducteur poly(aminoquinone) pour le stockage de l'énergie  

NASA Astrophysics Data System (ADS)

The electrooxidation of 5-amino-1,4-naphthoquinone (ANQ) in acetonitrile leads to conducting (10-1 S.cm-1) functionalized polymer films of polyaniline- type bearing one quinone group per ANQ moiety, electroactive in organic or aqueous solvents. The polymer exchanges cations during the redox process of quinones and is therefore interesting for lithium ions batteries devices. The measured specific charge is particularly hight with about 290 Ah/kg. L'oxydation électrochimique du 5-amino-1,4-naphtoquinone (ANQ) dans l'acétonitrile conduit à la formation de films conducteurs (10-1 S.cm-1) fonctionnalisés de structure type polyaniline portant une fonction quinone par motif ANQ, qui sont électroactifs en milieu aqueux comme en milieu organique. Le polymère échange des cations au cours du processus rédox des quinones et est ainsi intéressant pour les applications dans les accumulateurs au lithium. La charge spécifique mesurée de ce polymère est particulièrement élevée avec environ 290 Ah/kg.

Piro, B.; Pham, M. C.; Bazzaoui, E. A.; Lacroix, J.-C.; Lacaze, P.-C.; Novak, P.; Hass, O.

1998-06-01

208

Cobalt lawsone complexes: searching for new valence tautomers.  

PubMed

Bi-stable molecular systems presenting valence tautomerism are associated with the development of new functional materials, which can be used for applications in organic electric conductors, optoelectronic and molecular magnetic devices. The properties of these materials can be adjusted with slight chemical changes and can be induced by external stimuli. Typical examples of valence tautomer compounds are coordination complexes of Co and o-dioxolene ligands, notably quinone like ones. In the search for a new class of cobalt complexes presenting valence tautomerism we report herein the synthesis and characterization of five new coordination compounds of cobalt and 2-hydroxy-1,4-naphthoquinone (lawsone or shortly Law). Complexes [Co(Law)2(im)2]·C6H5CH3 (1), [Co(Law)2(py)2]·CH3OH (2), [Co(Law)2(phen)]·(C4H8O)2 (3), [Co(Law)2(2,2-bpy)]·C6H5CH3 (4) and [Co(Law)2(2,2-bpy)] (5) were synthesized and fully characterized by X-ray diffraction and EPR techniques in a wide range of temperatures and under illumination. Despite presenting similar molecular and geometry packing of the valence tautomer complexes of cobalt and o-dioxolenes, neither structural nor electronic evidence of valence tautomerism could be found in the Co and lawsone complexes. PMID:23423385

Ribeiro, Marcos A; Lanznaster, Maurício; Silva, Marcos M P; Resende, Jackson A L C; Pinheiro, Maurício V B; Krambrock, Klaus; Stumpf, Humberto O; Pinheiro, Carlos B

2013-04-21

209

Phytochemical screening and anti-inflammatory activity of Cnidoscolus quercifolius (Euphorbiaceae) in mice  

PubMed Central

Background: Cnidoscolus quercifolius is a species popularly known as favela and faveleira, and belonging to the Caatinga biome (semi-arid vegetation, Brazil), where is used in folk medicine as an anti-inflammatory. Objective: The aim was to evaluate the anti-inflammatory effect of the ethanolic extract from barks (Cqb-EtOH) and leaves (Cql-EtOH) of C. quercifolius in mice using experimental models of inflammation. Materials and Methods: The preliminary phytochemical analysis of the ethanolic extract was performed. The activity was evaluated by paw edema induced by carrageenan and leukocytes migration to the peritoneal cavity induced by carrageenan methods. Results: A preliminary analysis of Cqb-EtOH revealed that it contained coumarins, flavonoids, monoterpenes/diterpenes and naphthoquinones, while the Cql-EtOH showed positive reaction to coumarins, anthracene derivatives, flavonoids, lignans and triterpenes/steroids. Cqb-EtOH and Cql-EtOH (100, 200 and 400 mg/kg) inhibited significantly (P < 0.01) the increase in the edema volume after administration of carrageenan. In the peritonitis test, acute pretreatment with Cqb-EtOH and Cql-EtOH (100, 200 and 400 mg/kg) inhibited the leukocyte migration. Conclusions: It can be concluded that extracts from the barks and leaves of C. quercifolius have anti-inflammatory activity, which supports the popular use of this plant to treat inflammation. Thus, extracts has significant anti-inflammatory properties, which are related probably to inhibition of release of mediators of the inflammatory process.

de Araujo Gomes, Leandra Macedo; de Andrade, Thayne Mayra; Silva, Juliane Cabral; de Lima, Julianeli Tolentino; Quintans-Junior, Lucindo Jose; da Silva Almeida, Jackson Roberto Guedes

2014-01-01

210

Identification of naphthalene metabolism by white rot fungus Armillaria sp. F022.  

PubMed

Armillaria sp. F022, a white rot fungus isolated from tropical rain forest (Samarinda, Indonesia) was used to biodegrade naphthalene in cultured medium. Transformation of naphthalene by Armillaria sp. F022 which is able to use naphthalene, a two ring-polycyclic aromatic hydrocarbon (PAH) as a source of carbon and energy was investigated. The metabolic pathway was elucidated by identifying metabolites, biotransformation studies and monitoring enzyme activities in cell-free extracts. The identification of metabolites suggests that Armillaria sp. F022 initiates its attack on naphthalene by dioxygenation at its C-1 and C-4 positions to give 1,4-naphthoquinone. The intermediate 2-hydroxybenzaldehyde and salicylic acid, and the characteristic of the meta-cleavage of the resulting diol were identified in the long-term incubation. A part from typical metabolites of naphthalene degradation known from mesophiles, benzoic acid was identified as the next intermediate for the naphthalene pathway of this Armillaria sp. F022. Neither phthalic acid, catechol and cis,cis-muconic acid metabolites were detected in culture extracts. Several enzymes (manganese peroxidase, lignin peroxidase, laccase, 1,2-dioxygenase and 2,3-dioxygenase) produced by Armillaria sp. F022 were detected during the incubation. PMID:22894109

Hadibarata, Tony; Yusoff, Abdull Rahim Mohd; Aris, Azmi; Kristanti, Risky Ayu

2012-01-01

211

Screening of natural product biocides for control of non-indigenous species.  

PubMed

Several benzo-, naphtho- and anthraquinones were tested for their efficacy as biocides in controlling aquatic nuisance species in ships' ballast water. A requirement of this application was broad spectrum aquatic toxicity, coupled with a relatively rapid rate of degradation, in order to comply with coastal discharge requirements. Compounds were screened using a suite of toxicity bioassays designed to establish their relative toxicity to an array of planktonic organisms including larval bivalves Dreissena and Crassostrea, various developmental stages of the estuarine copepod Eurytemora affinis, brine shrimp larvae (Artemia salina), the freshwater invasive water flea Bythotrephes, larval sheepshead minnows CCyprinodon variegates) and two unicellular algal genera Isochrysis and Neochloris.. The majority of the data were recorded as the lowest concentration of the test compound resulting in complete mortality or inactivation of test organisms (LC ,m). The naphthoquinones juglone, plumbagin, menadione and naphthazarin showed the highest toxicity to the broadest range of organisms, often at levels much less than 1 mg l(-1), and most of the attention was focused on this group. While plumbagin and juglone appeared overall to be the most toxic compounds, it was concluded that menadione was probably the most cost-effective candidate compound for shipboard use for controlling invasive species in ballast water, particularly in view of the large volumes of water that would require treatment. PMID:17432383

Wright, D A; Dawson, R; Cutler, S J; Cutler, H G; Orano-Dawson, C E

2007-03-01

212

Quantification of para-phenylenediamine and heavy metals in henna dye.  

PubMed

Henna (Lawsonia inermis, family Lythraceae) is a shrub cultivated in India, Sri Lanka and North Africa and contains the active dye lawsone (2-hydroxy-1,4-naphthoquinone). Henna dye is obtained from the dried leaves, which are powdered and mixed with oil or water and are used to prepare hair and body dyes. Temporary henna tattoos are readily available worldwide, last on the skin for several weeks and offer a self-limited, convenient alternative to a permanent tattoo. The addition of para-phenylenediamine (PPD), which is widely recognised as a sensitizer, increases the risk of allergic contact dermatitis from henna tattoo mixtures, and a number of cases have been reported. We examined 15 henna samples available in Korea for the presence of PPD and heavy metals such as nickel, cobalt, chromium, lead and mercury using high-performance liquid chromatography (HPLC), atomic absorption spectroscopy (AAS), mercury analyser and inductively coupled plasma emission spectroscopy. PPD, nickel and cobalt were detected in 3, 11 and 4 samples, respectively. PMID:16842550

Kang, Ik-Joon; Lee, Mu-Hyoung

2006-07-01

213

Biopesticides from plants: Calceolaria integrifolia s.l.  

PubMed

The effects of persistent organic pollutants (POPs) on humans and biodiversity are multiple and varied. Nowadays environmentally-friendly pesticides are strongly preferred to POPs. It is noteworthy that the crop protection role of pesticides and other techniques, i.e. biopesticides, plant extracts, prevention methods, organic methods, evaluation of plant resistance to certain pests under an integrated pest management (IPM), could improve the risks and benefits which must be assessed on a sound scientific basis. For this directive it is crucial to bring about a significant reduction in the use of chemical pesticides, not least through the promotion of sustainable alternative solutions such as organic farming and IPM. Biopesticides are derived from natural materials such as animals, plants, bacteria, and certain minerals. Most of them are biodegradable in relatively short periods of time. On this regard, substances from Calceolaria species emerge as a strong alternative to the use of POPs. The American genus Calceolaria species are regarded both as a notorious weeds and popular ornamental garden plants. Some have medicinal applications. Other taxa of Calceolaria are toxic to insects and resistant to microbial attack. These properties are probably associated with the presence of terpenes, iridoids, flavonoids, naphthoquinones and phenylpropanoids previously demonstrated to have interesting biological activities. In this article a comprehensive evaluation of the potential utilization of Calceolaria species as a source of biopesticides is made. The chemical profile of selected members of the Chilean Calceolaria integrifolia sensu lato complex represents a significant addition to previous studies. New secondary metabolites were isolated, identified and tested for their antifeedant, insect growth regulation and insecticidal activities against Spodoptera frugiperda and Drosophila melanogaster. These species serve as a model of insect pests using conventional procedures. Additionally, bactericidal and fungicidal activity were determined. Dunnione mixed with gallic acid was the most active fungistatic and fungicidal combination encountered. Several compounds as isorhamnetin, combined with ferulic and gallic acid quickly reduced cell viability, but cell viability was recovered quickly and did not differ from that of the control. The effect of these mixtures on cultures of Aspergillus niger, Fusarium moniliforme, Fusarium sporotrichum, Rhizoctonia solani, and Trichophyton mentagrophytes, was sublethal. However, when fungistatic isorhamnetin and dunnione were combined with sublethal amounts of both ferulic and gallic acid, respectively, strong fungicidal activity against theses strains was observed. Thus, dunnione combined with gallic acid completely restricted the recovery of cell viability. This apparent synergistic effect was probably due to the blockade of the recovery process from induced-stress. The same series of phenolics (iridoids, flavonoids, naphthoquinones and phenylpropanoids) were also tested against the Gram-negative bacteria Escherichia coli, Enterobacter agglomerans, and Salmonella typhi, and against the Gram-positive bacteria Bacillus subtilis, Sarcinia lutea, and Staphylococcus aureus and their effects compared with those that of kanamycin. Mixtures of isorhamnetin/dunnione/kaempferol/ferulic/gallic acid in various combinations were found to have the most potent bactericidal and fungicidal activity with MFC between 10 and 50 ?g/ml. Quercetin was found to be the most potent fungistatic single compound with an MIC of 15 µg/ml. A time-kill curve study showed that quercetin was fungicidal against fungi assayed at any growth stage. This antifungal activity was slightly enhanced by combination with gallic acid. The primary antifungal action of the mixtures assayed likely comes from their ability to act as nonionic surfactants that disrupt the function of native membrane-associated proteins. Hence, the antifungal activity of isorhamnetin and other O-methyl flavonols appears to be mediated by biophysical processes. Maxim

Céspedes, Carlos L; Salazar, Juan R; Ariza-Castolo, Armando; Yamaguchi, Lydia; Avila, José G; Aqueveque, Pedro; Kubo, Isao; Alarcón, Julio

2014-07-01

214

Modeling Bimolecular Reactions and Transport in Porous Media Via Particle Tracking  

SciTech Connect

We use a particle-tracking method to simulate several one-dimensional bimolecular reactive transport experiments. In this numerical method, the reactants are represented by particles: advection and dispersion dominate the flow, and molecular diffusion dictates, in large part, the reactions. The particle/particle reactions are determined by a combination of two probabilities dictated by the physics of transport and energetics of reaction. The first is that reactant particles occupy the same volume over a short time interval. The second is the conditional probability that two collocated particles favorably transform into a reaction. The first probability is a direct physical representation of the degree of mixing in an advancing displacement front, and as such lacks empirical parameters except for the user-defined number of particles. This number can be determined analytically from concentration autocovariance, if this type of data is available. The simulations compare favorably to two physical experiments. In one, the concentration of product, 1,2-naphthoquinoe-4-aminobenzene (NQAB) from reaction between 1,2-naphthoquinone-4-sulfonic acid (NQS) and aniline (AN), was measured at the outflow of a column filled with glass beads at different times. In the other, the concentration distribution of reactants (CuSO_4 and EDTA^{4-}) and products (CuEDTA^{4-}) were quantified by snapshots of transmitted light through a column packed with cryloite sand. The thermodynamic rate coefficient in the latter experiment was 10^7 times greater than the former experiment, making it essentially instantaneous. When compared to the solution of the advection-dispersion-reaction equation (ADRE) with the well-mixed reaction coefficient, the experiments and the particle-tracking simulations showed on the order of 20% to 40% less overall product, which is attributed to poor mixing. The poor mixing also leads to higher product concentrations on the edges of the mixing zones, which the particle model simulates more accurately than the ADRE.

Dong Ding; David Benson; Amir Paster; Diogo Bolster

2012-01-01

215

Deuterium-Labeled Phylloquinone Has Tissue-Specific Conversion to Menaquinone-4 among Fischer 344 Male Rats12  

PubMed Central

Phylloquinone (PK) is converted into menaquinone-4 (MK-4) via side chain removal-addition. Stable isotope use is an effective approach to identify the tissue location of this conversion, which is currently unknown. Following a 14-d PK-deficient diet, male Fischer 344 rats (8 mo; n = 15) were fed 1.6 mg deuterium-labeled PK (L-PK) per kg diet for 0 (control), 1 d (PK-1d), and 7 d (PK-7d). Both L-PK and deuterium-labeled MK-4 (L-MK-4) were detected in tissues in PK-1d and PK-7d, although the results varied. Whereas some tissues had an overall increase in MK-4 in response to L-PK, total brain, testes, and fat MK-4 concentrations did not. In contrast, L-MK-4 concentrations increased in all 3 tissues. The deuterium label was found only on the L-MK-4 naphthoquinone ring, confirming the need for side chain removal for the formation of MK-4. Labeled menadione (MD) was detected in urine and serum in PK-1d and PK-7d, confirming its role as an intermediate. A Caco-2 cell monolayer model was used to study the role of the enterocytes in the conversion process. Neither MK-4 nor MD was detected in Caco-2 cells treated with PK. However, when Caco-2 cells were treated with MD, MK-4 was formed. Similarly, MK-4 was formed in response to MD-treated 293T kidney cells, but not HuH7 liver cells. These data demonstrate that MK-4 is the predominant form of vitamin K in multiple tissues, but there appears to be a tissue-specific regulation for the conversion of PK to MK-4. PMID:22437559

Al Rajabi, Ala; Booth, Sarah L.; Peterson, James W.; Choi, Sang Woon; Suttie, John W.; Shea, M. Kyla; Miao, Benchun; Grusak, Michael A.; Fu, Xueyan

2012-01-01

216

Mechanism-based inactivation of cytochrome P450 2A6 and 2A13 by Rhinacanthus nasutus constituents.  

PubMed

  Human cytochrome P450 CYP2A6 and CYP2A13 catalyze nicotine metabolisms and mediate activation of tobacco-specific carcinogens including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). In this study, we found rhinacanthins A, B, and C isolated from Rhinacanthus nasutus potentially inhibited coumarin 7-hydroxylation mediated by reconstituted purified recombinant CYP2A6 and CYP2A13. Rhinacanthins A-C are mechanism-based inactivators of CYP2A6 and CYP2A13 as they cause concentration, time and NADPH-dependent inhibition. Among the three rhinacanthins, rhinacanthin-B possessed highest inhibitory potency against CYP2A13 with apparent KI and kinact of 0.16 µM and 0.1 min(-1), respectively, while values of 0.44 µM and 0.12 min(-1) were found against CYP2A6. Rhinacanthin-C had least inhibition potency, with apparent KI and kinact of 0.97 µM and 0.07 min(-1) for CYP2A6, respectively, and values of 1.68 µM and 0.05 min(-1) for CYP2A13. Rhinacanthin-A inhibited CYP2A6 and CYP2A13 with apparent KI values of 0.69 and 0.42 µM, respectively and apparent kinact of 0.18 and 0.06 min(-1), respectively. The inhibition of both enzymes by rhinacanthins A-C could not be prevented by addition of trapping agents or reversed by dialysis or potassium ferricyanide. These findings demonstrated that rhinacanthins A-C, which are 1,4-naphthoquinone derivatives, irreversibly inhibited CYP2A6 and CYP2A13 in a mechanism-based inhibition mode. PMID:23903410

Pouyfung, Phisit; Prasopthum, Aruna; Sarapusit, Songklod; Srisook, Ekaruth; Rongnoparut, Pornpimol

2014-01-01

217

Cytotoxicity of lawsone and cytoprotective activity of antioxidants in catalase mutant Escherichia coli.  

PubMed

Lawsone is an active naphthoquinone derivative isolated from henna (Lawsonia inermis L.), a widely used hair dye. Previous study on the toxicity of lawsone remains unclear since the involvement of oxidative stress and the kind of ROS (reactive oxygen species) involved have not been fully resolved yet. This present study reports the cytotoxic effects of lawsone and henna. We carried out CAT assay (a zone of inhibition test of bacterial growth and colony-forming efficiency test of transformant Escherichia coli strains that express mammalian catalase gene derived from normal catalase mice (Cs(a)) and catalase-deficient mutant mice (Cs(b))), Ames mutagenicity assay and H(2)O(2) generation assay. Lawsone generated H(2)O(2) slightly in phosphate buffer system and was not mutagenic in Ames assay using TA 98, TA 100 and TA 102, both in the absence and presence of metabolic activation. Lawsone exposure inhibited the growth of both Cs(a) and Cs(b) strains in a dose-dependent manner. Mean zone diameter for Cs(a) was 9.75+/-0.96 mm and 12.75+/-1.5 mm for Cs(b). Natural henna leaves did not show toxic effects, whereas two out of four samples of marketed henna products were shown toxicity effects. Catalase abolished zone of inhibition (ZOI) of marketed henna products, eliminated ZOI of lawsone in a dose-dependent manner and low concentration of exogenous MnSOD and Cu/ZnSOD eliminated the toxicity. Histidine and DTPA, the metal chelator; BHA and low concentration of capsaicin, the inducer of NADH-quinone reductase, effectively protected Cs(a) and Cs(b) against lawsone in this study. We suggest that lawsone cytotoxicity is probably mediated, at least in part, by the release of O(2)(-), H(2)O(2) and OH(-). PMID:17442476

Sauriasari, Rani; Wang, Da-Hong; Takemura, Yoko; Tsutsui, Ken; Masuoka, Noriyoshi; Sano, Kuniaki; Horita, Masako; Wang, Bing-Ling; Ogino, Keiki

2007-06-01

218

Differentiation of SH-SY5Y cells to a neuronal phenotype changes cellular bioenergetics and the response to oxidative stress  

PubMed Central

Cell differentiation is associated with changes in metabolism and function. Understanding these changes during differentiation is important in the context of stem cell research, cancer, and neurodegenerative diseases. An early event in neurodegenerative diseases is the alteration of mitochondrial function and increased oxidative stress. Studies using both undifferentiated and differentiated SH-SY5Y neuroblastoma cells have shown distinct responses to cellular stressors, however the mechanisms remain unclear. We hypothesized that since the regulation of glycolysis and oxidative phosphorylation are modulated during cellular differentiation, this would change bioenergetic function and the response to oxidative stress. To test this, we used retinoic acid (RA) to induce differentiation of SH-SY5Y cells and assessed changes in cellular bioenergetics using extracellular flux analysis. After exposure to RA, the SH-SY5Y cells had an increased mitochondrial membrane potential, without changing mitochondrial number. Differentiated cells exhibited greater stimulation of mitochondrial respiration with uncoupling and an increased bioenergetic reserve capacity. The increased reserve capacity in the differentiated cells was suppressed by the inhibitor of glycolysis, 2-deoxy-D-glucose (2-DG). Furthermore, we found that differentiated cells were substantially more resistant to cytotoxicity and mitochondrial dysfunction induced by reactive lipid species 4-hydroxynonenal (HNE) or the reactive oxygen species generator 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). We then analyzed the levels of selected mitochondrial proteins and found an increase in complex IV subunits which we propose contributes to the increase in reserve capacity in the differentiated cells. Furthermore, we found an increase in MnSOD that could, at least in part, account for the increased resistance to oxidative stress. Our findings suggest that profound changes in mitochondrial metabolism and antioxidant defenses occur upon differentiation of neuroblastoma cells to a neuron-like phenotype. PMID:21945098

Schneider, Lonnie; Giordano, Samantha; Zelickson, Blake R.; Johnson, Michelle; Benavides, Gloria; Ouyang, Xiaosen; Fineberg, Naomi; Darley-Usmar, Victor M.; Zhang, Jianhua

2011-01-01

219

Molecular structures and biological evaluation of 2-chloro-3-(n-alkylamino)-1,4-napthoquinone derivatives as potent antifungal agents  

NASA Astrophysics Data System (ADS)

Derivatives of 2-chloro-3-(n-alkylamino)-1,4-naphthoquinone {n-alkyl: methyl; L-1, ethyl; L-2, propyl; L-3 and butyl; L-4} have been synthesized and characterized by elemental analysis, FT-IR, 1H NMR, UV-visible spectroscopy, LC-MS and single crystal X-ray diffraction studies. Antifungal activity of L-1 to L-4 has been evaluated against Candida tropicalis, Candida albicans and Cladosporium herbarum. The intramolecular hydrogen bonding affects the N-H vibrational frequency in L-2 (3273 cm-1). The single crystal X-ray structure reveal that L-1 and L-3 crystallizes in triclinic P-1, whereas L-2 crystallizes in orthorhombic Pca21 space group. An extensive intra and intermolecular hydrogen bonding interactions were observed in L-1 to L-3 which leads to molecular association. Intramolecular N-H⋯O hydrogen bonding were observed in L-1 to L-3. Moreover ?-? stacking interactions were observed between the quinonoid rings of L-1 and L-3, however no such interactions were observed in L-2. An electrochemical study showed molecular association of L-1 to L-4 in DMSO solution. Compounds L-1 to L-4 were found to be potent antifungal agents against all the three strains, especially against C. tropicalis. Amongst these promising antifungal candidates, L-1 showed better activity compared to the clinically administered antifungal drug Amphotericin B and Nitrofurantoin with MIC = 1.25 ?g ml-1 and MIC = 0.025 ?g ml-1 respectively against C. albicans. Structure and activity relationship (SAR) study suggest a Log P value of ˜2.0 and the cyclic voltammetry studies reveals additional chemical processes for L-1, which exhibits maximum activity against all fungal strains.

Pawar, Omkar; Patekar, Ashwini; Khan, Ayesha; Kathawate, Laxmi; Haram, Santosh; Markad, Ganesh; Puranik, Vedavati; Salunke-Gawali, Sunita

2014-02-01

220

Synthesis and characterization of 2-(n-alkylamino)-1,4-napthoquinone: Molecular structures of ethyl and hexyl derivatives  

NASA Astrophysics Data System (ADS)

We would like to introduce seven analogues of 2-(n-alkylamino)-1,4-napthoquinone (where n-alkyl is methyl in LH-1, ethyl in LH-2, propyl in LH-3, butyl in LH-4, pentyl in LH-5, hexyl in LH-6 and heptyl in LH-7). All the said analogues have been successfully synthesized from 1,4-naphthoquinone and well characterised using different spectroscopic techniques. Furthermore, in order to understand the mechanistic aspects of formation of LH-1-LH-7 compounds we could propose the mechanism. The FT-IR spectroscopic analysis of LH-1-LH-7 compounds indicating that the presence of characteristic band of Nsbnd H group at ?3340 cm-1. This band could assigned to existence of intramolecular hydrogen bonding interactions. The 13C-NMR spectroscopic technique has been used to study structural feature of LH-1-LH-7 compounds via HSQC, COSY and DEPT experiments. Finally, the structural aspects of the LH-2-LH-6 compounds have been confirmed by single crystal X-ray diffraction studies. We could observed that LH-2 compound crystallises in monoclinic space group P21/c, whereas LH-6 crystallises in triclinic P-1 space group. The molecule of LH-2 and LH-6 compounds forms dimers via Nsbnd H⋯O hydrogen bonding interaction while polymeric chains of dimers have been seen via Csbnd H⋯O hydrogen bonding. It is very interesting to note that the molecules of LH-6 possessing a ?-? stacking interaction between C⋯N of the neighbouring chains.

Patil, Rishikesh; Chadar, Dattatray; Chaudhari, Dinkar; Peter, Justin; Nikalje, Milind; Weyhermüller, Thomas; Salunke-Gawali, Sunita

2014-10-01

221

Modulation of T cell proliferation and cytokine response by Plumbagin, extracted from Plumbago zeylanica in collagen induced arthritis  

PubMed Central

Background The extracts of Plumbago zeylanica have been used in China and other Asian countries as folk medicine for the treatment of cancer, rheumatoid arthritis and dysmenorrhoea. Effect of Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) purified from Plumbago zeylanica on Con A induced T cell proliferation was studied in spleen cells from collagen induced arthritic DBA/1 mice. Methods The DBA/1 mice (five per each group) were immunized with 0.1 mL of collagen (emulsified in CFA) by intradermal injection at the base of the tail. On day 20, mice were given a booster dose of collagen (emulsified in IFA) through the same route. Plumbagin was given at different concentrations (3.3, 6.6, 13.3 mg/kg body weight) intraperitoneally. Control mice received olive oil alone. The Con A induced T cell proliferative responses of arthritic and Plumbagin treated mice were studied by cell culture experiments using tritiated Thymidine. In addition the cytokine levels were estimated from the in vitro spleen culture supernatants of arthritic mice primed with different concentrations of Plumbagin by ELISA. Results Plumbagin enhanced the decreased Con A induced T cell proliferation and Interleukin-2 production in arthritic mice. Moreover elevated levels of IFN- ? were found to be decreased in Plumbagin treated spleen cell culture supernatants. Subclasses of IgG were found to be decreased by Plumbagin treatment, IgG2a reduction seems to be more prominent. Conclusion The results obtained in the current study indicate that Plumbagin is very effective in the mechanism based treatment of Rheumatoid arthritis. PMID:22085488

2011-01-01

222

Secondary Metabolites from Plants Inhibiting ABC Transporters and Reversing Resistance of Cancer Cells and Microbes to Cytotoxic and Antimicrobial Agents  

PubMed Central

Fungal, bacterial, and cancer cells can develop resistance against antifungal, antibacterial, or anticancer agents. Mechanisms of resistance are complex and often multifactorial. Mechanisms include: (1) Activation of ATP-binding cassette (ABC) transporters, such as P-gp, which pump out lipophilic compounds that have entered a cell, (2) Activation of cytochrome p450 oxidases which can oxidize lipophilic agents to make them more hydrophilic and accessible for conjugation reaction with glucuronic acid, sulfate, or amino acids, and (3) Activation of glutathione transferase, which can conjugate xenobiotics. This review summarizes the evidence that secondary metabolites (SM) of plants, such as alkaloids, phenolics, and terpenoids can interfere with ABC transporters in cancer cells, parasites, bacteria, and fungi. Among the active natural products several lipophilic terpenoids [monoterpenes, diterpenes, triterpenes (including saponins), steroids (including cardiac glycosides), and tetraterpenes] but also some alkaloids (isoquinoline, protoberberine, quinoline, indole, monoterpene indole, and steroidal alkaloids) function probably as competitive inhibitors of P-gp, multiple resistance-associated protein 1, and Breast cancer resistance protein in cancer cells, or efflux pumps in bacteria (NorA) and fungi. More polar phenolics (phenolic acids, flavonoids, catechins, chalcones, xanthones, stilbenes, anthocyanins, tannins, anthraquinones, and naphthoquinones) directly inhibit proteins forming several hydrogen and ionic bonds and thus disturbing the 3D structure of the transporters. The natural products may be interesting in medicine or agriculture as they can enhance the activity of active chemotherapeutics or pesticides or even reverse multidrug resistance, at least partially, of adapted and resistant cells. If these SM are applied in combination with a cytotoxic or antimicrobial agent, they may reverse resistance in a synergistic fashion. PMID:22536197

Wink, Michael; Ashour, Mohamed L.; El-Readi, Mahmoud Zaki

2012-01-01

223

Shikonin Exerts Antitumor Activity via Proteasome Inhibition and Cell Death Induction in vitro and in vivo  

PubMed Central

Dysregulation of the ubiquitin-proteasome pathway plays an essential role in tumor growth and development. Shikonin, a natural naphthoquinone isolated from the traditional Chinese medicine Zi Cao (gromwell), has been reported to possess tumor cell-killing activity, and results from a clinical study using a shikonin-containing mixture demonstrated its safety and efficacy for the treatment of late-stage lung cancer. In the present study, we reported that shikonin is an inhibitor of tumor proteasome activity in vitro and in vivo. Our computational modeling predicts that the carbonyl carbons C1 and C4 of shikonin potentially interact with the catalytic site of ?5 chymotryptic subunit of the proteasome. Indeed, shikonin potently inhibits the chymotrypsin-like activity of purified 20S proteasome (IC50 12.5 ?mol/L) and tumor cellular 26S proteasome (IC50 between 2-16 ?mol/L). Inhibition of the proteasome by shikonin in murine hepatoma H22, leukemia P388 and human prostate cancer PC-3 cultures resulted in accumulation of ubiquitinated proteins and several proteasome target proapoptotic proteins (I?B-?, Bax and p27), followed by induction of cell death. Shikonin treatment resulted in tumor growth inhibition in both H22 allografts and PC-3 xenografts, associated with suppression of the proteasomal activity and induction of cell death in vivo. Finally, shikonin treatment significantly prolonged the survival period of mice bearing P388 leukemia. Our results indicate that the tumor proteasome is one of the cellular targets of shikonin, and inhibition of the proteasome activity by shikonin contributes to its anti-tumor property. PMID:19165859

Yang, Huanjie; Zhou, Ping; Huang, Hongbiao; Chen, Di; Ma, Ningfang; Cui, Cindy Qiuzhi; Shen, Shouxing; Dong, Weihua; Zhang, Xiaoyan; Lian, Wen; Wang, Xuejun; Dou, Q. Ping; Liu, Jinbao

2009-01-01

224

Induction of extracellular hydroxyl radical production by white-rot fungi through quinone redox cycling.  

PubMed

A simple strategy for the induction of extracellular hydroxyl radical (OH) production by white-rot fungi is presented. It involves the incubation of mycelium with quinones and Fe(3+)-EDTA. Succinctly, it is based on the establishment of a quinone redox cycle catalyzed by cell-bound dehydrogenase activities and the ligninolytic enzymes (laccase and peroxidases). The semiquinone intermediate produced by the ligninolytic enzymes drives OH production by a Fenton reaction (H(2)O(2) + Fe(2+) --> OH + OH(-) + Fe(3+)). H(2)O(2) production, Fe(3+) reduction, and OH generation were initially demonstrated with two Pleurotus eryngii mycelia (one producing laccase and versatile peroxidase and the other producing just laccase) and four quinones, 1,4-benzoquinone (BQ), 2-methoxy-1,4-benzoquinone (MBQ), 2,6-dimethoxy-1,4-benzoquinone (DBQ), and 2-methyl-1,4-naphthoquinone (menadione [MD]). In all cases, OH radicals were linearly produced, with the highest rate obtained with MD, followed by DBQ, MBQ, and BQ. These rates correlated with both H(2)O(2) levels and Fe(3+) reduction rates observed with the four quinones. Between the two P. eryngii mycelia used, the best results were obtained with the one producing only laccase, showing higher OH production rates with added purified enzyme. The strategy was then validated in Bjerkandera adusta, Phanerochaete chrysosporium, Phlebia radiata, Pycnoporus cinnabarinus, and Trametes versicolor, also showing good correlation between OH production rates and the kinds and levels of the ligninolytic enzymes expressed by these fungi. We propose this strategy as a useful tool to study the effects of OH radicals on lignin and organopollutant degradation, as well as to improve the bioremediation potential of white-rot fungi. PMID:19376892

Gómez-Toribio, Víctor; García-Martín, Ana B; Martínez, María J; Martínez, Angel T; Guillén, Francisco

2009-06-01

225

The naphthoquinol oxidizing cytochrome bc1 complex of the hyperthermophilic knallgasbacterium Aquifex aeolicus: properties and phylogenetic relationships.  

PubMed

Phylogenetic analysis of constituent proteins of Rieske/cytochrome b complexes [Schütz et al. (2000) J. Mol. Biol. 300, 663-675] indicated that the respective enzyme from the hyperthermophile Aquifex (A.) aeolicus is closely related to proteobacterial counterparts, in disagreement with positioning of its parent species on small subunit rRNA trees. An assessment of the details and possible reasons for this discrepancy necessitates a thorough understanding of the biochemical and biophysical properties of the enzyme in addition to the bioinformatic data. The cytochrome bc(1) complex from A. aeolicus, which is part of the "Knallgasreaction" pathway, was therefore studied in membranes and in detergent-solubilized, isolated complex. Hemes b(L) (E(m,7) = -190 mV; g(z)= 3.7), b(H) (E(m,7) = -60 mV; g(z )= 3.45), and c(1) (E(m,7) = +160 mV; g(z )= 3.55) were identified by EPR and optical spectroscopy in combination with electrochemical methods. Two electrochemically distinct (E(m,7) = +95 mV; E(m,7) = +210 mV) Rieske centers were detected in membranes, and the +210 mV species was shown to correspond to the Rieske center of the cyt bc(1) complex. The gene coding for this latter Rieske protein was heterologously expressed in Escherichia coli, and the resulting protein was characterized in detail. The pool quinone of A. aeolicus was determined to be naphthoquinone. The redox poises of the individual electron-transfer steps are compared to those of other Rieske/cyt b complexes. The Aquifex enzyme was found to represent the only extant naphthoquinol oxidizing true cyt bc(1) complex described so far. An improved scenario for the phylogenetic positioning of the Aquifex cyt bc(1) complex is proposed. PMID:12962505

Schütz, Michael; Schoepp-Cothenet, Barbara; Lojou, Elisabeth; Woodstra, Mireille; Lexa, Doris; Tron, Pascale; Dolla, Alain; Durand, Marie-Claire; Stetter, Karl Otto; Baymann, Frauke

2003-09-16

226

Molecular structures and antiproliferative activity of side-chain saturated and homologated analogs of 2-chloro-3-(n-alkylamino)-1,4-napthoquinone  

NASA Astrophysics Data System (ADS)

Side chain homologated derivatives of 2-chloro-3-(n-alkylamino)-1,4-naphthoquinone {n-alkyl: pentyl; L-5, hexyl; L-6, heptyl; L-7 and octyl; L-8} have been synthesized and characterized by elemental analysis, FT-IR, 1H NMR, UV-visible spectroscopy and LC-MS. Compounds, L-4, {n-alkyl: butyl; L-4}, L-6 and L-8 have been characterized by single crystal X-ray diffraction studies. The single crystal X-ray structures reveal that L-4 and L-8 crystallizes in P21 space group, while L-6 in P21/c space group. Molecules of L-4 and L-8 from polymeric chains through Csbnd H⋯O and Nsbnd H⋯O close contacts. L-6 is a dimer formed by Nsbnd H⋯O interaction. Slipped ?-? stacking interactions are observed between quinonoid and benzenoid rings of L-4 and L-8. Orientations of alkyl group in L-4 and L-8 is on same side of the chain and polymeric chains run opposite to one another to form zip like structure to the alkyl groups. Antiproliferative activities of L-1 to L-8{n-alkyl: methyl; L-1, ethyl; L-2, propyl; L-3 and butyl; L-4} were studied in cancer cells of colon (COLO205), brain (U87MG) and pancreas (MIAPaCa2) where L-1, L-2 and L-3 were active in MIAPaCa2 (L-1 = L-2 > L-3) and COLO205 (L-2 = L-3 > L-1) and inactive in U87MG. From antiproliferative studies with compounds L-1 to L-8 it can be concluded that homologation of 2-chloro-3-(n-alkylamino)-1,4-napthoquinone with saturated methyl groups yielded tissue specific compounds such as L-2 (for MIAPaCa2) and L-3 (for COLO205) with optimal activity.

Pal, Sanjima; Jadhav, Mahesh; Weyhermüller, Thomas; Patil, Yogesh; Nethaji, M.; Kasabe, Umesh; Kathawate, Laxmi; Konkimalla, V. Badireenath; Salunke-Gawali, Sunita

2013-10-01

227

Induction of intrinsic apoptosis pathway in colon cancer HCT-116 cells by novel 2-substituted-5,6,7,8-tetrahydronaphthalene derivatives.  

PubMed

2-Acetyl tetralin (1) reacted with N,N-dimethylformamide dimethylacetal (DMF-DMA) to afford the enaminone 3. The reaction of 3 with piperidine and morpholine afforded the trans enaminone 5a,b, respectively. Compound 3 was treated with primary aromatic amines to give secondary enaminones 6a-e. The enaminone 3 reacted with acetylglycine and hippuric acid to yield pyranones 10a, b, respectively. The reaction of enaminone 3 with 1,4-benzoquinone and 1,4-naphthoquinone gave benzofuranyl tetralin derivatives 14a,b, respectively. Also, when 3 reacted with 5-amino-3-phenyl-1H-pyrazole 15a and 5-amino-1,2,3-triazole 15b, it afforded the new pyrazolo[1,5-a]pyrimidine 17a and 1,2,3-triazolo[1,5-a]pyrimidine 17b, respectively. While the reaction of 3 with pyrimidines 18a, b resulted in the formation of pyrido[2,3-d]pyrimidine derivatives 20a, b, respectively. Investigations of the cytotoxic effect of those compounds against different human cell lines indicated that some compounds showed high selective cytotoxicity against colon cancer HCT-116 cells. Some of these compounds led to DNA damaging and fragmentation that was associated with the induction of apoptosis via mitochondrial pathway. This pathway is initiated by the impairment of mitochondrial transmembrane potential (??m) and in response to that the mitochondria released cytochrome c increased, that in turn activated caspase-9 and caspase-3 and induced apoptosis. Compounds 17b and 20b were promising anti-cancer agents that induced intrinsic apoptosis pathway in colon cancer cells. PMID:24657569

Gamal-Eldeen, Amira M; Hamdy, Nehal A; Abdel-Aziz, Hatem A; El-Hussieny, Enas A; Fakhr, Issa M I

2014-04-22

228

High-performance liquid chromatography for quantification of plumbagin, an anti-Helicobacter pylori compound of Plumbago zeylanica L.  

PubMed

The plant Plumbago zeylanica L. is a semi-climbing shrub that grows throughout Asia and Africa. In our previous study, P. zeylanica L. exhibited high anti-Helicobacter pylori and good bactericidal activities over a wide pH range (pH 2-7). Plumbagin - the major ingredient derived from the roots of P. zeylanica L. - is a naphthoquinone compound. In this study, we investigated plumbagin's anti-H. pylori activity and developed a reversed-phase high-performance liquid chromatography (HPLC) method for quantification of plumbagin from P. zeylanica L. We also observed that plumbagin has strong anti-H. pylori activity, with 0.02-0.16 mg/ml as minimum inhibitory concentrations and 0.16-1.28 mg/ml as minimum bactericidal concentrations. Reversed-phase HPLC was performed with a gradient mobile phase composed of water and methanol, and peaks were detected at 254 nm. Standard curves were linearized in the range of from 10 to 200 microg/ml (regression coefficient r2 = 0.99995). After spikes of 50, 100, and 150 microg/ml of plumbagin standard solution, recovery rates were between 97.45 and 99.24%. Both intra- and inter-day precisions had coefficient variation of less than 1% at concentrations of 50, 100, and 150 microg/ml. The limits of detection and quantitation were 0.02 and 0.06 microg/ml, respectively. Based on validation results, this analytical method is a precise, accurate and stable method to quantify plumbagin derived from P. zeylanica L. PMID:16257295

Wang, Yuan-Chuen; Huang, Tung-Liang

2005-11-11

229

Effects of atovaquone and other inhibitors on Pneumocystis carinii dihydroorotate dehydrogenase.  

PubMed Central

Dihydroorotate dehydrogenase (DHOD) is a pyrimidine biosynthetic enzyme which is usually directly linked to the mitochondrial respiratory chain. Antimalarial naphthoquinones such as atovaquone (566c80) inhibit malarial DHOD by inhibiting electron transport. Since atovaquone also has therapeutic activity against Pneumocystis carinii, the P. carinii DHOD may also be an important drug target. Organisms were obtained from immunosuppressed rats, incubated for 24 h in a short-term in vitro culture system, and then lysed. P. carinii lysates catalyzed the generation of orotate from dihydroorotate at a rate of 852 pmol/mg of protein per min. Control preparations made from uninfected mice showed much less total enzymatic activity and enzyme specific activity. As expected, P. carinii DHOD activity was susceptible to respiratory inhibitors such as cyanide, antimycin A, and salicylhydroxamic acid (SHAM). Susceptibility to SHAM suggests the presence of an alternative oxidase. In contrast, neither pentamidine nor 5-hydroxy-6-demethylprimaquine (5H6DP), a quinone metabolite of primaquine, inhibited the enzyme. Atovaquone inhibited DHOD by 76.3% at 100 microM and 36.5% at 10 microM. A similar degree of inhibition was found when the organisms were preincubated with the drug. Atovaquone inhibited P. carinii growth in vitro at a somewhat lower concentration (between 0.3 and 3 microM). In contrast, Plasmodium falciparum growth and enzyme activity are susceptible to nanomolar concentrations of atovaquone. Thus, while it is possible that atovaquone acts by inhibiting the P. carinii electron transport chain, the possibility of another drug target cannot be excluded. PMID:7726490

Ittarat, I; Asawamahasakda, W; Bartlett, M S; Smith, J W; Meshnick, S R

1995-01-01

230

Cr(VI) Reduction and Cr(III) Immobilization by Acinetobacter sp. HK-1 with the Assistance of a Novel Quinone/Graphene Oxide Composite.  

PubMed

Cr(VI) biotreatment has attracted a substantial amount of interest due to its cost effectiveness and environmental friendliness. However, the slow Cr(VI) bioreduction rate and the formed organo-Cr(III) in solution are bottlenecks for biotechnology application. In this study, a novel strain, Acinetobacter sp. HK-1, capable of reducing Cr(VI) and immobilizing Cr(III) was isolated. Under optimal conditions, the Cr(VI) reduction rate could reach 3.82 mg h(-1) g cell(-1). To improve the Cr(VI) reduction rate, two quinone/graphene oxide composites (Q-GOs) were first prepared via a one-step covalent chemical reaction. The results showed that 2-amino-3-chloro-1,4-naphthoquinone-GO (NQ-GO) exhibited a better catalytic performance in Cr(VI) reduction compared to 2-aminoanthraquinone-GO. Specifically, in the presence of 50 mg L(-1) NQ-GO, a Cr(VI) removal rate of 190 mg h(-1) g cell(-1), which was the highest rate obtained, was achieved. The increased Cr(VI) reduction rate is mainly the result of NQ-GO significantly increasing the Cr(VI) reduction activity of cell membrane proteins containing dominant Cr(VI) reductases. X-ray photoelectron spectroscopy analysis found that Cr(VI) was reduced to insoluble Cr(III), which was immobilized by glycolipids secreted by strain HK-1. These findings indicate that the application of strain HK-1 and NQ-GO is a promising strategy for enhancing the treatment of Cr(VI)-containing wastewater. PMID:25296002

Zhang, Hai-Kun; Lu, Hong; Wang, Jing; Zhou, Ji-Ti; Sui, Meng

2014-11-01

231

Isolation of cellular membranes from lignin-producing tissues of Norway spruce and analysis of redox enzymes.  

PubMed

There are no earlier reports with successful isolation of plasma membranes from lignin-forming tissues of conifers. A method to isolate cellular membranes from extracellular lignin-producing tissue-cultured cells and developing xylem of Norway spruce was optimized. Modifications to the homogenization buffer were needed to obtain membranes from these phenolics-rich tissues. Membranes were separated by aqueous polymer two-phase partitioning. Chlorophyll a determination, marker enzyme assays and western blot analyses using antibodies for each membrane type showed that mitochondrial, chloroplastic and to a certain extent also ER and Golgi membranes were efficiently diminished from the upper phase, but tonoplast and plasma membranes distributed evenly between the upper and lower phases. Redox enzymes present in the partially purified membrane fractions were assayed in order to reveal the origin of H2 O2 needed for lignification. The membranes of spruce contained enzymes able to generate superoxide in the presence of NAD(P)H. Besides members of the flavodoxin and flavodoxin-like family proteins, cytochrome b5, cytochrome P450 and several stress responsive proteins were identified by nitroblue tetrazolium staining of isoelectric focusing gels and by mass spectrometry. Naphthoquinones juglone and menadione increased superoxide production in activity-stained gels. Some juglone-activated enzymes were preferentially using NADH. With NADH, menadione activated only some of the enzymes that juglone did, whereas with NADPH the activation patterns were identical. Duroquinone, a benzoquinone, did not affect superoxide production. Superoxide dismutase, ascorbate peroxidase, catalase and an acidic class III peroxidase isoenzyme were detected in partially purified spruce membranes. The possible locations and functions of these enzymes are discussed. PMID:24730578

Kärkönen, Anna; Meisrimler, Claudia-Nicole; Takahashi, Junko; Väisänen, Enni; Laitinen, Teresa; Jiménez Barboza, Luis Alexis; Holmström, Sami; Salonvaara, Sadette; Wienkoop, Stefanie; Fagerstedt, Kurt V; Lüthje, Sabine

2014-12-01

232

Toxicological effects of polycyclic aromatic hydrocarbons and their derivatives on respiratory cells  

NASA Astrophysics Data System (ADS)

Polycyclic aromatic hydrocarbons (PAHs) are found in ambient aerosols and particulate matter. Experimental studies have shown that PAHs and related chemicals can induce toxicological effects. The present study aimed to investigate the effects of PAHs and their derivatives on the respiratory and immune systems and the underlying mechanisms. The human bronchial epithelial cell line BEAS-2B was exposed to PAHs and their derivatives, and the cytotoxicity and proinflammatory protein expression were then investigated. A cytotoxic effect was observed in BEAS-2B exposed to PAH derivatives such as naphthoquinone (NQ), phenanthrenequinone (PQ), 1-nitropyrene (1-NP), and 1-aminopyrene (1-AP). In addition, 1,2-NQ and 9,10-PQ showed more effective cytotoxicity than 1,4-NQ and 1,4-PQ, respectively. Pyrene showed a weak cytotoxic effect. On the other hand, naphthalene and phenanthrene showed no significant effects. Pyrene, 1-NP, and 1-AP also increased intercellular adhesion molecule-1 expression and interleukin-6 production in BEAS-2B. The increase was partly suppressed by protein kinase inhibitors such as the epidermal growth factor receptor-selective tyrosine kinase inhibitor and nuclear receptor antagonists such as the thyroid hormone receptor antagonist. The present study suggests that the toxicological effects of chemicals may be related to the different activities resulting from their structures, such as numbers of benzene rings and functional groups. Furthermore, the chemical-induced increase in proinflammatory protein expression in bronchial epithelial cells was possibly a result of the activation of protein kinase pathways and nuclear receptors. The increase may partly contribute to the adverse health effects of atmospheric PAHs.

Koike, Eiko; Yanagisawa, Rie; Takano, Hirohisa

2014-11-01

233

Potential of herbs in skin protection from ultraviolet radiation  

PubMed Central

Herbs have been used in medicines and cosmetics from centuries. Their potential to treat different skin diseases, to adorn and improve the skin appearance is well-known. As ultraviolet (UV) radiation can cause sunburns, wrinkles, lower immunity against infections, premature aging, and cancer, there is permanent need for protection from UV radiation and prevention from their side effects. Herbs and herbal preparations have a high potential due to their antioxidant activity, primarily. Antioxidants such as vitamins (vitamin C, vitamin E), flavonoids, and phenolic acids play the main role in fighting against free radical species that are the main cause of numerous negative skin changes. Although isolated plant compounds have a high potential in protection of the skin, whole herbs extracts showed better potential due to their complex composition. Many studies showed that green and black tea (polyphenols) ameliorate adverse skin reactions following UV exposure. The gel from aloe is believed to stimulate skin and assist in new cell growth. Spectrophotometer testing indicates that as a concentrated extract of Krameria triandra it absorbs 25 to 30% of the amount of UV radiation typically absorbed by octyl methoxycinnamate. Sesame oil resists 30% of UV rays, while coconut, peanut, olive, and cottonseed oils block out about 20%. A “sclerojuglonic” compound which is forming from naphthoquinone and keratin is the reaction product that provides UV protection. Traditional use of plant in medication or beautification is the basis for researches and making new trends in cosmetics. This review covers all essential aspects of potential of herbs as radioprotective agents and its future prospects. PMID:22279374

Korac, Radava R.; Khambholja, Kapil M.

2011-01-01

234

Complete phenotypic recovery of an Alzheimer's disease model by a quinone-tryptophan hybrid aggregation inhibitor.  

PubMed

The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated beta-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp), combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Abeta oligomerization and fibrillization, as well as the cytotoxic effect of Abeta oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Abeta while immuno-staining of the 3(rd) instar larval brains showed a significant reduction in Abeta accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Abeta. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease. PMID:20559435

Scherzer-Attali, Roni; Pellarin, Riccardo; Convertino, Marino; Frydman-Marom, Anat; Egoz-Matia, Nirit; Peled, Sivan; Levy-Sakin, Michal; Shalev, Deborah E; Caflisch, Amedeo; Gazit, Ehud; Segal, Daniel

2010-01-01

235

Comparison of calculated and experimental isotope edited FTIR difference spectra for purple bacterial photosynthetic reaction centers with different quinones incorporated into the QA binding site  

PubMed Central

Previously we have shown that ONIOM type (QM/MM) calculations can be used to simulate isotope edited FTIR difference spectra for neutral ubiquinone in the QA binding site in Rhodobacter sphaeroides photosynthetic reaction centers. Here we considerably extend upon this previous work by calculating isotope edited FTIR difference spectra for reaction centers with a variety of unlabeled and 18O labeled foreign quinones incorporated into the QA binding site. Isotope edited spectra were calculated for reaction centers with 2,3-dimethoxy-5,6-dimethyl-1,4-benzoquinone (MQ0), 2,3,5,6-tetramethyl-1, 4-benzoquinone (duroquinone, DQ), and 2,3-dimethyl-l,4-naphthoquinone (DMNQ) incorporated, and compared to corresponding experimental spectra. The calculated and experimental spectra agree well, further demonstrating the utility and applicability of our ONIOM approach for calculating the vibrational properties of pigments in protein binding sites. The normal modes that contribute to the bands in the calculated spectra, their composition, frequency, and intensity, and how these quantities are modified upon 18O labeling, are presented. This computed information leads to a new and more detailed understanding/interpretation of the experimental FTIR difference spectra. Hydrogen bonding to the carbonyl groups of the incorporated quinones is shown to be relatively weak. It is also shown that there is some asymmetry in hydrogen bonding, accounting for 10–13 cm?1 separation in the frequencies of the carbonyl vibrational modes of the incorporated quinones. The extent of asymmetry in H-bonding could only be established by considering the spectra for various types of quinones incorporated into the QA binding site. The quinones listed above are “tail-less.” Spectra were also calculated for reaction centers with corresponding “tail” containing quinones incorporated, and it is found that replacement of the quinone methyl group by a phytyl or prenyl chain does not alter ONIOM calculated spectra. PMID:24009618

Zhao, Nan; Lamichhane, Hari P.; Hastings, Gary

2013-01-01

236

Secondary Metabolites from Plants Inhibiting ABC Transporters and Reversing Resistance of Cancer Cells and Microbes to Cytotoxic and Antimicrobial Agents.  

PubMed

Fungal, bacterial, and cancer cells can develop resistance against antifungal, antibacterial, or anticancer agents. Mechanisms of resistance are complex and often multifactorial. Mechanisms include: (1) Activation of ATP-binding cassette (ABC) transporters, such as P-gp, which pump out lipophilic compounds that have entered a cell, (2) Activation of cytochrome p450 oxidases which can oxidize lipophilic agents to make them more hydrophilic and accessible for conjugation reaction with glucuronic acid, sulfate, or amino acids, and (3) Activation of glutathione transferase, which can conjugate xenobiotics. This review summarizes the evidence that secondary metabolites (SM) of plants, such as alkaloids, phenolics, and terpenoids can interfere with ABC transporters in cancer cells, parasites, bacteria, and fungi. Among the active natural products several lipophilic terpenoids [monoterpenes, diterpenes, triterpenes (including saponins), steroids (including cardiac glycosides), and tetraterpenes] but also some alkaloids (isoquinoline, protoberberine, quinoline, indole, monoterpene indole, and steroidal alkaloids) function probably as competitive inhibitors of P-gp, multiple resistance-associated protein 1, and Breast cancer resistance protein in cancer cells, or efflux pumps in bacteria (NorA) and fungi. More polar phenolics (phenolic acids, flavonoids, catechins, chalcones, xanthones, stilbenes, anthocyanins, tannins, anthraquinones, and naphthoquinones) directly inhibit proteins forming several hydrogen and ionic bonds and thus disturbing the 3D structure of the transporters. The natural products may be interesting in medicine or agriculture as they can enhance the activity of active chemotherapeutics or pesticides or even reverse multidrug resistance, at least partially, of adapted and resistant cells. If these SM are applied in combination with a cytotoxic or antimicrobial agent, they may reverse resistance in a synergistic fashion. PMID:22536197

Wink, Michael; Ashour, Mohamed L; El-Readi, Mahmoud Zaki

2012-01-01

237

2-Methoxystypandrone ameliorates brain function through preserving BBB integrity and promoting neurogenesis in mice with acute ischemic stroke.  

PubMed

2-Methoxystypandrone (2-MS), a naphthoquinone, has been shown to display an immunomodulatory effect in a cellular model. To explore whether 2-MS could protect mice against cerebral ischemic/reperfusion (I/R)-induced brain injury, we evaluated 2-MS's protective effects on an acute ischemic stroke by inducing a middle cerebral artery occlusion/reperfusion (MCAO) injury in murine model. Treatment of mice that have undergone I/R injury with 2-MS (10-100 ?g/kg, i.v.) at 2 h after MCAO enhanced survival rate and ameliorated neurological deficits, brain infarction, neural dysfunction and massive oxidative stress, due to an enormous production of free radicals and breakdown of blood-brain barrier (BBB) by I/R injury; this primarily occurred with extensive infiltration of CD11b-positive inflammatory cells and upexpression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and p65 nuclear factor-kappa B (NF-?B). All of these pathological changes were diminished by 2-MS; 2-MS also intensively limited cortical infarction and promoted upexpression of neurodevelopmental genes near peri-infarct cortex and endogenous neurogenesis near subgranular zone of hippocampal dentate gyrus and the subventricular zone, most possibly by inactivation of GSK3? which in turn upregulating ?-catenin, Bcl-2 adam11 and adamts20. We conclude that 2-MS blocks inflammatory responses by impairing NF-?B signaling to limit the inflammation and oxidative stress for preservation of BBB integrity; 2-MS also concomitantly promotes neurodevelopmental protein expression and endogenous neurogenesis through inactivation of GSK3? to enhance ?-catenin signaling for upexpression of neuroprotective genes and proteins. PMID:24342702

Chern, Chang-Ming; Wang, Yea-Hwey; Liou, Kuo-Tong; Hou, Yu-Chang; Chen, Chien-Chih; Shen, Yuh-Chiang

2014-02-01

238

Opposing effects of nitroxide free radicals in Escherichia coli mutants deficient in DNA repair.  

PubMed

Nitroxide free radicals have been previously shown to function as superoxide dismutase (SOD) mimics and to protect bacterial and mammalian cells against oxidative damage, particularly from superoxide and hydrogen peroxide. Although nitroxides are generally considered to be non-toxic nor mutagenic, there is no agreement regarding their potential adverse effect. Some toxic effects were observed upon using high concentration of six-membered ring derivatives. Conflicting evidence has also been reported regarding the mutagenic activity of nitroxides toward Salmonella typhimurium. It was also demonstrated that nitroxides exert two opposing effects on exonuclease III deficient cells of Escherichia coli upon exposure to naphthoquinones. The attempts to use nitroxides as contrast agents in nuclear magnetic resonance imaging (MRI) and as a new class of anti-oxidants underscore the need to examine their potential adverse effects. Since nitroxides protected xthA cells from DNA scission caused by H2O2, it was anticipated that they would provide even greater protection for recA DNA repair-deficient cells of E. coli, which are more sensitive to H2O2-induced oxidative stress. The results of the present study showed that: (a) nitroxides exert bactericidal and bacteriostatic effects on recA but not on xthA or wild-type E. coli K12 cells; (b) nitroxides and H2O2 act synergistically on recA cells, both under aerobic and hypoxic conditions; (c) the nitroxide-induced toxicity in recA cells and the synergistic effect with H2O2 were not accompanied by a decrease in the cellular level of reduced glutathione; (d) TEMPAMINE protected against DNA scission induced by H2O2 and 1,10-ortho-phenanthroline chelate of Cu(II) in xthA cells, but potentiated DNA double-strand breakage in recA cells. PMID:8605254

Wang, G; Godinger, D; Aronovitch, J; Samuni, A

1996-02-01

239

Novel anti-inflammatory function of NSC95397 by the suppression of multiple kinases.  

PubMed

NSC95397 (2,3-bis-[(2-hydroxyethyl)thio]-1,4-naphthoquinone) is a CDC25 inhibitor with anti-cancer properties. Since the anti-inflammatory activity of this compound has not yet been explored, the aim of this study was to examine whether this compound is able to modulate the inflammatory process. Toll like receptor (TLR)-mediated inflammatory responses were induced by lipopolysaccharide (LPS), a TLR4 ligand, and pam3CSK, a TLR2 ligand, in peritoneal macrophages and RAW264.7. The molecular mechanism of NSC95397's anti-inflammatory activity was studied using immunoblotting analysis, nuclear fractionation, immunoprecipitation, overexpression strategies, luciferase reporter gene assays, and kinase assays. NSC95397 dose-dependently suppressed the production of nitric oxide (NO), tumor necrosis factor (TNF)-?, and prostaglandin (PG)E2, and diminished the mRNA expression of inflammatory genes such as inducible NO synthase (iNOS), cyclooxygenase (COX)-2, interferon (IFN)-?, and TNF-? in peritoneal macrophages and RAW264.7 cells that were stimulated by LPS and pam3CSK. This compound also clearly blocked the activation of NF-?B (p65), AP-1 (c-Fos/c-Jun), and IRF-3 in LPS-treated RAW264.7 cells and TRIF- and MyD88-overexpressing HEK293 cells. In addition, biochemical and molecular approaches revealed that this compound targeted AKT, IKK?/?, MKK7, and TBK1. Therefore, these results suggest that the anti-inflammatory function of NSC95397 can be attributed to its inhibition of multiple targets such as AKT, IKK?/?, MKK7, and TBK1. PMID:24468133

Yang, Yanyan; Yang, Woo Seok; Yu, Tao; Yi, Young-Su; Park, Jae Gwang; Jeong, Deok; Kim, Ji Hye; Oh, Jeong Su; Yoon, Keejung; Kim, Jong-Hoon; Cho, Jae Youl

2014-03-15

240

Plasticity of the Quinone-binding Site of the Complex II Homolog Quinol:Fumarate Reductase*  

PubMed Central

Respiratory processes often use quinone oxidoreduction to generate a transmembrane proton gradient, making the 2H+/2e? quinone chemistry important for ATP synthesis. There are a variety of quinones used as electron carriers between bioenergetic proteins, and some respiratory proteins can functionally interact with more than one quinone type. In the case of complex II homologs, which couple quinone chemistry to the interconversion of succinate and fumarate, the redox potentials of the biologically available ubiquinone and menaquinone aid in driving the chemical reaction in one direction. In the complex II homolog quinol:fumarate reductase, it has been demonstrated that menaquinol oxidation requires at least one proton shuttle, but many of the remaining mechanistic details of menaquinol oxidation are not fully understood, and little is known about ubiquinone reduction. In the current study, structural and computational studies suggest that the sequential removal of the two menaquinol protons may be accompanied by a rotation of the naphthoquinone ring to optimize the interaction with a second proton shuttling pathway. However, kinetic measurements of site-specific mutations of quinol:fumarate reductase variants show that ubiquinone reduction does not use the same pathway. Computational docking of ubiquinone followed by mutagenesis instead suggested redundant proton shuttles lining the ubiquinone-binding site or from direct transfer from solvent. These data show that the quinone-binding site provides an environment that allows multiple amino acid residues to participate in quinone oxidoreduction. This suggests that the quinone-binding site in complex II is inherently plastic and can robustly interact with different types of quinones. PMID:23836905

Singh, Prashant K.; Sarwar, Maruf; Maklashina, Elena; Kotlyar, Violetta; Rajagukguk, Sany; Tomasiak, Thomas M.; Cecchini, Gary; Iverson, Tina M.

2013-01-01

241

Development of Enantioselective Synthetic Routes to (-)-Kinamycin F and (-)-Lomaiviticin Aglycon  

PubMed Central

The development of enantioselective synthetic routes to (–)-kinamycin F (9) and (–)-lomaiviticin aglycon (6) is described. The diazotetrahydrobenzo[b]fluorene (diazofluorene) functional group of the targets was prepared by fluoride-mediated coupling of a ?-trimethylsilylmethyl-?,?-unsaturated ketone (38) with an oxidized naphthoquinone (19), palladium-catalyzed cyclization (39?37), and diazo transfer (37?53). The D-ring precursors 60 and 68 were prepared from m-cresol and 3-ethylphenol, respectively. Coupling of the ?-trimethylsilylmethyl-?,?-unsaturated ketone 60 with the juglone derivative 61, cyclization, and diazo transfer, provided the advanced diazofluorene 63, which was elaborated to (–)-kinamycin F (9) in three steps. The diazofluorene 87 was converted to the C2-symmetric lomaiviticin aglycon precursor 91 by enoxysilane formation and oxidative dimerization with manganese tris(hexafluoroacetylacetonate) (94, 26%). The stereochemical outcome is attributed to the steric bias engendered by the mesityl acetal of 87 and contact ion pairing of the intermediates. The coupling product 91 was deprotected (tert-butylhydrogen peroxide, trifluoroacetic acid–dichloromethane) to form the chain isomer of lomaiviticin aglycon 98, which cyclizes to (–)-lomaiviticin aglycon (6, 39–41% overall). The scope of the fluoride-mediated coupling process is delineated (nine products, average yield = 72%, Table 2); a related enoxysilane quinonylation reaction is also described (10 products, average yield = 77%, Table 1). We establish that dimeric diazofluorenes undergo hydrodediazotization 3-fold faster then related monomeric diazofluorenes (Table 6). The simple diazofluorene 103 is a potent inhibitor of ovarian cancer stem cells (IC50 = 500 nM). PMID:23030272

Woo, Christina M.; Gholap, Shivajirao L.; Lu, Liang; Kaneko, Miho; Li, Zhenwu; Ravikumar, P. C.; Herzon, Seth B.

2012-01-01

242

NMR Studies Reveal an Unexpected Binding Site for a Redox Inhibitor of AP Endonuclease 1  

PubMed Central

AP endonuclease 1 (APE1) is a multi-faceted protein with essential roles in DNA repair and transcriptional regulation. APE1 (Ref-1) activates many transcription factors (TF), including AP-1 and NF-?B. While the mechanism of APE1 redox activity remains unknown, it may involve reduction of an oxidized Cys in the TF DNA-binding domain. Several small molecules inhibit APE1-mediated TF activation, including the quinone derivative E3330. It has been proposed some inhibitors bind near C65, a residue suggested to be important for TF activation, but the binding site has not been determined for any inhibitor. Remarkably, NMR and molecular docking studies here reveal E3330 binds in the DNA repair active site of APE1, far removed from C65. Accordingly, AP endonuclease activity is substantially inhibited by E3330 (100 ?M), suggesting that E3330 may not selectively inhibit APE1 redox activity in cells, in contrast with previous proposals. A naphthoquinone analog of E3330, RN7-60, binds a site removed from both C65 and the repair active-site. While a detailed understanding of how these inhibitors work requires further studies into the mechanism of redox activity, our results do not support proposals that E3330 binds selectively (and slowly) to locally unfolded APE1, or that E3330 promotes formation of disulfide bonds in APE1. Rather, we suggest E3330 may suppress a conformational change needed for redox activity, disrupt productive APE1-TF binding, or block the proposed redox chaperone activity of APE1. Our results provide the first structural information for any APE1 redox inhibitor, and could facilitate development of improved inhibitors for research and perhaps clinical purposes. PMID:22032234

Manvilla, Brittney A.; Wauchope, Orrette; Seley-Radtke, Katherine L.; Drohat, Alexander C.

2011-01-01

243

A functional description of CymA, an electron-transfer hub supporting anaerobic respiratory flexibility in Shewanella.  

PubMed

CymA (tetrahaem cytochrome c) is a member of the NapC/NirT family of quinol dehydrogenases. Essential for the anaerobic respiratory flexibility of shewanellae, CymA transfers electrons from menaquinol to various dedicated systems for the reduction of terminal electron acceptors including fumarate and insoluble minerals of Fe(III). Spectroscopic characterization of CymA from Shewanella oneidensis strain MR-1 identifies three low-spin His/His co-ordinated c-haems and a single high-spin c-haem with His/H(2)O co-ordination lying adjacent to the quinol-binding site. At pH 7, binding of the menaquinol analogue, 2-heptyl-4-hydroxyquinoline-N-oxide, does not alter the mid-point potentials of the high-spin (approximately -240 mV) and low-spin (approximately -110, -190 and -265 mV) haems that appear biased to transfer electrons from the high- to low-spin centres following quinol oxidation. CymA is reduced with menadiol (E(m) = -80 mV) in the presence of NADH (E(m) = -320 mV) and an NADH-menadione (2-methyl-1,4-naphthoquinone) oxidoreductase, but not by menadiol alone. In cytoplasmic membranes reduction of CymA may then require the thermodynamic driving force from NADH, formate or H2 oxidation as the redox poise of the menaquinol pool in isolation is insufficient. Spectroscopic studies suggest that CymA requires a non-haem co-factor for quinol oxidation and that the reduced enzyme forms a 1:1 complex with its redox partner Fcc3 (flavocytochrome c3 fumarate reductase). The implications for CymA supporting the respiratory flexibility of shewanellae are discussed. PMID:22458729

Marritt, Sophie J; Lowe, Thomas G; Bye, Jordan; McMillan, Duncan G G; Shi, Liang; Fredrickson, Jim; Zachara, John; Richardson, David J; Cheesman, Myles R; Jeuken, Lars J C; Butt, Julea N

2012-06-15

244

Composition of Secondary Organic Aerosol from the Photolysis of 1-Nitronaphthalene  

NASA Astrophysics Data System (ADS)

Nitro-substituted polycyclic aromatic hydrocarbons are of interest due to their associated mutagenic and carcinogenic effects. 1-Nitronaphthalene is emitted directly from combustion processes such as vehicle exhaust, but is also formed through the reaction of naphthalene with the hydroxyl or nitrate radical in the presence of NOx. Photolysis has previously been demonstrated to be the major degradation pathway for 1-nitronaphthalene in the troposphere. In this study, a series of simulation chamber experiments has been performed to investigate the chemical composition of secondary organic aerosol (SOA) formed through the direct photolysis of 1-nitronaphthalene using an Aerosol Time-Of-Flight Mass Spectrometer (ATOFMS, TSI). SOA forms rapidly with a yield of up to 50% depending on precursor concentration and photolysis rate. Along with expected products such as naphthoquinone and nitronaphthol, condensed species exhibiting mass spectra consistent with the presence of four aromatic rings were also observed. It is proposed that these species may be formed through dimerization of naphthoxy radicals generated during the photolysis process. Further evidence to support this mechanism was obtained when 1-nitronaphthalene was photolyzed in the presence of excess nitrobenzene. Dimers were then formed containing three aromatic rings, consistent with the reaction of phenoxy and naphthoxy radicals. The molecular formulae of the dimers were also confirmed by collecting SOA on filters and analysing the extracts off-line using an LTQ Orbitrap Velos mass spectrometer (Thermo-Fisher Scientific), fitted with a TriVersa NanoMate chip-based electrospray ionization source (Advion Biosystems). The rapid formation of condensable dimers through the self-reaction of naphthoxy radicals represents a previously unreported potential pathway to SOA formation. Analogous mechanisms may also be important for other nitrated polycyclic aromatic hydrocarbons.

Wenger, J.; Healy, R.; Chen, Y.; Kalberer, M.; Kourtchev, I.

2012-12-01

245

Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B  

PubMed Central

Protein Tyrosine Phosphatases (PTPs) that function as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing Protein Tyrosine Phosphatase1B (PTP1B) abundance not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high fat feeding. PTP1B inhibitors such as Formylchromone derivatives, 1, 2-Naphthoquinone derivatives and Oxalyl aryl amino benzoic derivatives may eventually find an important clinical role as insulin sensitizers in the management of Type-II Diabetes and metabolic syndrome. We have carried out docking of modified oxalyl aryl amino benzoic acid derivatives into three dimensional structure of PTP1B using BioMed CAChe 6.1. These compounds exhibit good selectivity for PTP1B over most of phosphatases in selectivity panel such as SHP-2, LAR, CD45 and TCPTP found in literature. This series of compounds identified the amino acid residues such as Gly220 and Arg221 are important for achieving specificity via H-bonding interactions. Lipophilic side chain of methionine in modified oxalyl aryl amino benzoic acid derivative [1b (a2, b2, c1, d)] lies in closer vicinity of hydrophobic region of protein consisted of Meth258 and Phe52 in comparison to active ligand. Docking Score in [1b (a2, b2, c1, d)] is -131.740Kcal/mol much better than active ligand score -98.584Kcal/mol. This information can be exploited to design PTP1B specific inhibitors. PMID:19238234

Verma, Neelam; Mittal, Minakshi; Verma, Raman kumar

2008-01-01

246

Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B.  

PubMed

Protein Tyrosine Phosphatases (PTPs) that function as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing Protein Tyrosine Phosphatase1B (PTP1B) abundance not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high fat feeding. PTP1B inhibitors such as Formylchromone derivatives, 1, 2-Naphthoquinone derivatives and Oxalyl aryl amino benzoic derivatives may eventually find an important clinical role as insulin sensitizers in the management of Type-II Diabetes and metabolic syndrome. We have carried out docking of modified oxalyl aryl amino benzoic acid derivatives into three dimensional structure of PTP1B using BioMed CAChe 6.1. These compounds exhibit good selectivity for PTP1B over most of phosphatases in selectivity panel such as SHP-2, LAR, CD45 and TCPTP found in literature. This series of compounds identified the amino acid residues such as Gly220 and Arg221 are important for achieving specificity via H-bonding interactions. Lipophilic side chain of methionine in modified oxalyl aryl amino benzoic acid derivative [1b (a2, b2, c1, d)] lies in closer vicinity of hydrophobic region of protein consisted of Meth258 and Phe52 in comparison to active ligand. Docking Score in [1b (a2, b2, c1, d)] is -131.740Kcal/mol much better than active ligand score -98.584Kcal/mol. This information can be exploited to design PTP1B specific inhibitors. PMID:19238234

Verma, Neelam; Mittal, Minakshi; Verma, Raman Kumar

2008-01-01

247

Mutagenicity of 80 chemicals in Escherichia coli tester strains IC203, deficient in OxyR, and its oxyR(+) parent WP2 uvrA/pKM101: detection of 31 oxidative mutagens.  

PubMed

Strain IC203, deficient in OxyR, and its oxyR(+) parent WP2 uvrA/pKM101 (denoted IC188) are the basis of a new bacterial reversion assay, the WP2 Mutoxitest, which has been used in the evaluation of 80 chemicals for oxidative mutagenicity. The following 31 oxidative mutagens were recognized by their greater mutagenic response in IC203 than in IC188: (1) peroxides: hydrogen peroxide (HP), t-butyl hydroperoxide (BOOH) and cumene hydroperoxide (COOH); (2) benzoquinones (BQ): 2-methyl-1,4-BQ, 2,6-dimethyl-1,4-BQ and 2,3, 5,6-tetramethyl-1,4-BQ; (3) naphthoquinones (NQ): 1,4-NQ, 2-methyl-1, 4-NQ and 2-hydroxy-1,4-NQ; (4) phenol derivatives: catechol, hydroquinone, pyrogallol, 1,2,4-benzenetriol, t-butylhydroquinone, gallic acid and 4-aminophenol; (5) catecholamines: DL- and L-dopa, DL- and L-epinephrine, dopamine and L-norepinephrine; (6) thiols: L-cysteine methyl ester, L-cysteine ethyl ester, L-penicillamine and dithiothreitol; (7) diverse: 3,4-dihydroxyphenylacetic acid, hypoxanthine and xanthine, both in the presence of xanthine oxidase, L-ascorbic acid plus copper (II) and phenazine methosulfate. Among these oxidative mutagens, 25 were found to be uniquely positive in IC203. With the exception of BOOH and COOH, mutagenesis by all oxidative mutagens was inhibited by catalase present in rat liver S9, indicating that it is mediated by HP generation, probably in autoxidation reactions. These catalase-sensitive oxidative mutagens were poor inducers of mutations derived from 8-oxoguanine lesions, whereas such mutations were efficiently induced by organic hydroperoxides. The results support the usefulness of incorporating IC203 in the bacterial battery for testing of chemicals. The well-characterized oxidative mutagens available with the use of the WP2 Mutoxitest may serve as a reference in studies on the genotoxicity of oxidative stress. PMID:10771270

Martínez, A; Urios, A; Blanco, M

2000-04-13

248

Mode-of-Action Uncertainty for Dual-Mode Carcinogens:Lower Bounds for Naphthalene-Induced Nasal Tumors in Rats Implied byPBPK and 2-Stage Stochastic Cancer Risk Models  

SciTech Connect

As reflected in the 2005 USEPA Guidelines for Cancer Risk Assessment, some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate ''linear'' (genotoxic) vs. ''nonlinear'' (nongenotoxic) approaches to low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient to parameterize a biologically based model that reliably extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach--similar to that used in reference dose procedures for classic toxicity endpoints--can address MOA uncertainty in a way that avoids explicit modeling of low-dose risk as a function of administered or internal dose. Even when a ''nonlinear'' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was illustrated for the rodent carcinogen naphthalene. Bioassay data, supplemental toxicokinetic data, and related physiologically based pharmacokinetic and 2-stage stochastic carcinogenesis modeling results all clearly indicate that naphthalene is a DMOA carcinogen. Plausibility bounds on rat-tumor-type specific DMOA-related uncertainty were obtained using a 2-stage model adapted to reflect the empirical link between genotoxic and cytotoxic effects of the most potent identified genotoxic naphthalene metabolites, 1,2- and 1,4-naphthoquinone. Resulting bounds each provided the basis for a corresponding ''uncertainty'' factor <1 appropriate to apply to estimates of naphthalene risk obtained by linear extrapolation under a default genotoxic MOA assumption. This procedure is proposed as scientifically credible method to address MOA uncertainty for DMOA carcinogens.

Bogen, K T

2007-01-30

249

Mode-of-Action Uncertainty for Dual-Mode Carcinogens: A Bounding Approach for Naphthalene-Induced Nasal Tumors in Rats Based on PBPK and 2-Stage Stochastic Cancer Risk Models  

SciTech Connect

A relatively simple, quantitative approach is proposed to address a specific, important gap in the appr approach recommended by the USEPA Guidelines for Cancer Risk Assessment to oach address uncertainty in carcinogenic mode of action of certain chemicals when risk is extrapolated from bioassay data. These Guidelines recognize that some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate 'linear' (genotoxic) vs. 'nonlinear' (nongenotoxic) approaches to low low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient t to parameterize a biologically based model that reliably o extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach - similar to that used in reference dose procedures for classic toxicity endpoints - can address MOA uncertainty in a way that avoids explicit modeling of low low-dose risk as a function of administere administered or internal dose. Even when a 'nonlinear' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was i illustrated llustrated for a likely DMOA rodent carcinogen naphthalene, specifically to the issue of risk extrapolation from bioassay data on naphthalene naphthalene-induced nasal tumors in rats. Bioassay data, supplemental toxicokinetic data, and related physiologically based p pharmacokinetic and 2 harmacokinetic 2-stage stochastic carcinogenesis modeling results all clearly indicate that naphthalene is a DMOA carcinogen. Plausibility bounds on rat rat-tumor tumor-type specific DMOA DMOA-related uncertainty were obtained using a 2-stage model adapted to reflec reflect the empirical link between genotoxic and cytotoxic effects of t the most potent identified genotoxic naphthalene metabolites, 1,2 1,2- and 1,4 1,4-naphthoquinone. Bound Bound-specific 'adjustment' factors were then used to reduce naphthalene risk estimated by linear ex extrapolation (under the default genotoxic MOA assumption), to account for the DMOA trapolation exhibited by this compound.

Bogen, K T

2007-05-11

250

Incorporation of a high potential quinone reveals that electron transfer in Photosystem I becomes highly asymmetric at low temperature.  

PubMed

Photosystem I (PS I) has two nearly identical branches of electron-transfer co-factors. Based on point mutation studies, there is general agreement that both branches are active at ambient temperature but that the majority of electron-transfer events occur in the A-branch. At low temperature, reversible electron transfer between P(700) and A(1A) occurs in the A-branch. However, it has been postulated that irreversible electron transfer from P(700) through A(1B) to the terminal iron-sulfur clusters F(A) and F(B) occurs via the B-branch. Thus, to study the directionality of electron transfer at low temperature, electron transfer to the iron-sulfur clusters must be blocked. Because the geometries of the donor-acceptor radical pairs formed by electron transfer in the A- and B-branch differ, they have different spin-polarized EPR spectra and echo-modulation decay curves. Hence, time-resolved, multiple-frequency EPR spectroscopy, both in the direct-detection and pulse mode, can be used to probe the use of the two branches if electron transfer to the iron-sulfur clusters is blocked. Here, we use the PS I variant from the menB deletion mutant strain of Synechocyctis sp. PCC 6803, which is unable to synthesize phylloquinone, to incorporate 2,3-dichloro-1,4-naphthoquinone (Cl(2)NQ) into the A(1A) and A(1B) binding sites. The reduction midpoint potential of Cl(2)NQ is approximately 400 mV more positive than that of phylloquinone and is unable to transfer electrons to the iron-sulfur clusters. In contrast to previous studies, in which the iron-sulfur clusters were chemically reduced and/or point mutations were used to prevent electron transfer past the quinones, we find no evidence for radical-pair formation in the B-branch. The implications of this result for the directionality of electron transfer in PS I are discussed. PMID:22246442

Mula, Sam; Savitsky, Anton; Möbius, Klaus; Lubitz, Wolfgang; Golbeck, John H; Mamedov, Mahir D; Semenov, Alexey Yu; van der Est, Art

2012-06-01

251

Purification and characterization of a membrane-bound enzyme complex from the sulfate-reducing archaeon Archaeoglobus fulgidus related to heterodisulfide reductase from methanogenic archaea.  

PubMed

Heterodisulfide reductase (Hdr) is a unique disulfide reductase that plays a key role in the energy metabolism of methanogenic archaea. The genome of the sulfate-reducing archaeon Archaeoglobus fulgidus encodes several proteins of unknown function with high sequence similarity to the catalytic subunit of Hdr. Here we report on the purification of a multisubunit membrane-bound enzyme complex from A. fulgidus that contains a subunit related to the catalytic subunit of Hdr. The purified enzyme is a heme/iron-sulfur protein, as deduced by UV/Vis spectroscopy, EPR spectroscopy, and the primary structure. It is composed of four different subunits encoded by a putative transcription unit (AF499, AF501-AF503). A fifth protein (AF500) encoded by this transcription unit could not be detected in the purified enzyme preparation. Subunit AF502 is closely related to the catalytic subunit HdrD of Hdr from Methanosarcina barkeri. AF501 encodes a membrane-integral cytochrome, and AF500 encodes a second integral membrane protein. AF499 encodes an extracytoplasmic iron-sulfur protein, and AF503 encodes an extracytoplasmic c-type cytochrome with three heme c-binding motifs. All of the subunits show high sequence similarity to proteins encoded by the dsr locus of Allochromatium vinosum and to subunits of the Hmc complex from Desulfovibrio vulgaris. The heme groups of the enzyme are rapidly reduced by reduced 2,3-dimethyl-1,4-naphthoquinone (DMNH2), which indicates that the enzyme functions as a menaquinol-acceptor oxidoreductase. The physiological electron acceptor has not yet been identified. Redox titrations monitored by EPR spectroscopy were carried out to characterize the iron-sulfur clusters of the enzyme. In addition to EPR signals due to [4Fe-4S]+ clusters, signals of an unusual paramagnetic species with g values of 2.031, 1.994, and 1.951 were obtained. The paramagnetic species could be reduced in a one-electron transfer reaction, but could not be further oxidized, and shows EPR properties similar to those of a paramagnetic species recently identified in Hdr. In Hdr this paramagnetic species is specifically induced by the substrates of the enzyme and is thought to be an intermediate of the catalytic cycle. Hence, Hdr and the A. fulgidus enzyme not only share sequence similarity, but may also have a similar active site and a similar catalytic function. PMID:11952791

Mander, Gerd J; Duin, Evert C; Linder, Dietmar; Stetter, Karl O; Hedderich, Reiner

2002-04-01

252

Interaction of ascorbate with photosystem I.  

PubMed

Ascorbate is one of the key participants of the antioxidant defense in plants. In this work, we have investigated the interaction of ascorbate with the chloroplast electron transport chain and isolated photosystem I (PSI), using the EPR method for monitoring the oxidized centers [Formula: see text] and ascorbate free radicals. Inhibitor analysis of the light-induced redox transients of P700 in spinach thylakoids has demonstrated that ascorbate efficiently donates electrons to [Formula: see text] via plastocyanin. Inhibitors (DCMU and stigmatellin), which block electron transport between photosystem II and Pc, did not disturb the ascorbate capacity for electron donation to [Formula: see text]. Otherwise, inactivation of Pc with CN(-) ions inhibited electron flow from ascorbate to [Formula: see text]. This proves that the main route of electron flow from ascorbate to [Formula: see text] runs through Pc, bypassing the plastoquinone (PQ) pool and the cytochrome b 6 f complex. In contrast to Pc-mediated pathway, direct donation of electrons from ascorbate to [Formula: see text] is a rather slow process. Oxidized ascorbate species act as alternative oxidants for PSI, which intercept electrons directly from the terminal electron acceptors of PSI, thereby stimulating photooxidation of P700. We investigated the interaction of ascorbate with PSI complexes isolated from the wild type cells and the MenB deletion strain of cyanobacterium Synechocystis sp. PCC 6803. In the MenB mutant, PSI contains PQ in the quinone-binding A1-site, which can be substituted by high-potential electron carrier 2,3-dichloro-1,4-naphthoquinone (Cl2NQ). In PSI from the MenB mutant with Cl2NQ in the A1-site, the outflow of electrons from PSI is impeded due to the uphill electron transfer from A1 to the iron-sulfur cluster FX and further to the terminal clusters FA/FB, which manifests itself as a decrease in a steady-state level of [Formula: see text]. The addition of ascorbate promoted photooxidation of P700 due to stimulation of electron outflow from PSI to oxidized ascorbate species. Thus, accepting electrons from PSI and donating them to [Formula: see text], ascorbate can mediate cyclic electron transport around PSI. The physiological significance of ascorbate-mediated electron transport is discussed. PMID:24965848

Trubitsin, Boris V; Mamedov, Mahir D; Semenov, Alexey Yu; Tikhonov, Alexander N

2014-11-01

253

Investigations of solvent properties and solvent effects on chemical equilibria and reaction rates  

NASA Astrophysics Data System (ADS)

Thermodynamic and structural properties computed via simulations of pure liquids and dilute solutions are routinely used as a metric of accuracy for condensed-phase force fields and in the development and testing of new methodology. Additionally, reliable modeling of solvent systems is critical to investigations of physical phenomena, such as the elucidation of solvent effects on chemical equilibria and reaction rates. This dissertation highlights a series of studies that span these topics. The Lennard-Jones 12-6 functional form, often invoked to model van der Waals interactions, has been argued to be too repulsive at short internuclear separations. Monte Carlo simulations of organic liquids at various temperatures and pressures show that this function, in conjunction with OPLS parameters, is capable of reproducing experimental densities. In order to address potential cumulative deviations of computed properties and conformational differences between the gas phase and pure liquids, Monte Carlo simulations have been carried out for the homologous n-alkane series C4H10-C12H26 using the OPLS-AA force field. Favorable structural motifs of longer alkanes were also investigated to study self solvation in the gas phase. Next, an overview of the computation of free energy changes in solution using perturbation theory, overlap sampling, and related approximate methods is presented. Results are provided for free energies of hydration of OPLS-AA substituted benzenes in TIP4P water. For comparable amounts of computer time, the double-wide and overlap sampling methods yield very similar results. QM/MM simulations of the Diels-Alder reactions of cyclopentadiene with 1,4-naphthoquinone, methyl vinyl ketone, and acrylonitrile have been carried out at the water-vacuum interface and in the gas phase. The relative free energies of activation and transition structure geometries at the interface were intermediate between those calculated in the gas phase and in bulk water, consistent with estimated experimental rate constants. Energy pair distributions reveal a loss of slightly favorable solute-solvent pair contacts but retention of stronger interactions upon transition from bulk to surface hydration. These strong interactions cause the methyl vinyl ketone transition structure to preferentially orient its carbonyl toward the surface, while the other transition structures prefer orientations parallel to the surface.

Defeo, Laura Lynn Thomas

254

Biosynthesis of vitamin K1 (phylloquinone) by plant peroxisomes and its integration into signaling molecule synthesis pathways.  

PubMed

Vitamin K1 (phylloquinone) is a substituted membrane-anchored naphthoquinone that functions as an essential electron carrier in photosystem I in photosynthetic organisms. While plants can synthesize phylloquinone de novo, humans rely on vitamin K1 uptake from green leafy vegetables as a precursor for the synthesis of its structural derivative, menaquinone-4 (vitamin K2). In vertebrates, menaquinone-4 serves as an enzymatic co-factor that is required for posttranslational protein modification, i.e. the ?-carboxylation of glutamate residues in specific proteins involved in blood coagulation, bone metabolism and vascular biology. Comprehensive knowledge of the subcellular compartmentalization of vitamin K biosynthesis in plants, pathway regulation and its integration in cellular metabolic networks is important to design functional food with elevated vitamin levels and health benefits to human consumers. It had long been assumed that plants obtained all enzymes for phylloquinone biosynthesis from the ancient cyanobacterial endosymbiont and that, upon gene transfer to the nucleus, all biosynthetic enzymes were re-directed to the plastid. This view, however, has been recently challenged by the exclusive localization of the 6th pathway enzyme (MenB/NS) to peroxisomes in Arabidopsis. Soon afterwards, not only the preceding enzyme, acyl-activating enzyme 14 (MenE/AAE14), but also the succeeding thioesterase (DHNAT) were also shown to be peroxisomal. Phylogenetic analysis revealed a heterogeneous evolutionary origin of the peroxisomal enzymes. Phylloquinone biosynthesis reveals several branching points leading to the synthesis of important defence signalling molecules, such as salicylic acid and benzoic acid derivatives. Recent research data demonstrate that, of the two phenylalanine-dependent pathways for benzoic and salicylic acid biosynthesis, the CoA-dependent ?-oxidative pathway, which is peroxisomal, is the major route. Hence, peroxisomes emerge as an important cell compartment for the interconnected networks of phylloquinone, benzoic and salicylic acid biosynthesis. Numerous mechanisms to regulate intermediate flux and the fine-tuned inducible production of secondary metabolites, including signalling molecules, await their characterization at the molecular level. PMID:23821151

Reumann, Sigrun

2013-01-01

255

Search for constituents with neurotrophic factor-potentiating activity from the medicinal plants of paraguay and Thailand.  

PubMed

20 medicinal plants of Paraguay and 3 medicinal plants of Thailand were examined on nerve growth factor (NGF)-potentiating activities in PC12D cells. The trail results demonstrated that the methanol extracts of four plants, Verbena littoralis, Scoparia dulcis, Artemisia absinthium and Garcinia xanthochymus, markedly enhanced the neurite outgrowth induced by NGF from PC12D cells. Furthermore, utilizing the bioactivity-guided separation we successfully isolated 32, 4 and 5 constituents from V. littoralis, S. dulcis and G. xanthochymus, respectively, including nine iridoid and iridoid glucosides (1-9), two dihydrochalcone dimers (10 and 11), two flavonoids and three flavonoid glycosides (12-16), two sterols (17 and 18), ten triterpenoids (19-28), five xanthones (29-33), one naphthoquinone (34), one benzenepropanamide (35), four phenylethanoid glycosides (36-39) and two other compounds (40 and 41). Among which, 15 compounds (1-4, 10-11, 14-18, 29-31 and 34) were new natural products. The results of pharmacological trails verified that littoralisone (1), gelsemiol (5), 7a-hydroxysemperoside aglucone (6), verbenachalcone (10), littorachalcone (11), stigmast-5-ene 3beta,7alpha,22alpha-triol (18), ursolic acid (19), 3beta-hydroxyurs-11-en-28,13beta-olide (24), oleanolic acid (25), 2alpha,3beta-dihydroxyolean-12-en-28-oic acid (26), 1,4,5,6-tetrahydroxy-7,8-di(3-methylbut-2-enyl)xanthone (29), 1,2,6-trihydroxy-5-methoxy-7-(3-methylbut-2-enyl)xanthone (30), 1,3,5,6-tetrahydroxy-4,7,8-tri(3-methyl-2-butenyl)xanthone (31), 12b-hydroxy-des-D-garcigerrin A (32), garciniaxanthone E (33) and (4R)-4,9-dihydroxy-8-methoxy-alpha-lapachone (34) elicited marked enhancement of NGF-mediated neurite outgrowth in PC12D cells. These substances may contribute to the basic study and the medicinal development for the neurodegenerative disorder. PMID:15235225

Li, Yushan; Ohizumi, Yasushi

2004-07-01

256

The in vitro anthelmintic effects of plumbagin on newly excysted and 4-weeks-old juvenile parasites of Fasciola gigantica.  

PubMed

The effect of plumbagin (PB, 5-hydroxy-2-methyl-1,4-naphthoquinone) against newly excysted juveniles (NEJs) and 4-weeks-old immature parasites of Fasciola gigantica were compared with triclabendazole (TCZ). The anthelmintic efficacy of 1, 10 and 100?g/ml of PB or TCZ following incubation in vitro for 1-24h was compared using a combination of relative motility (RM), survival index (SI) and larval migration inhibition (LMI) assays for parasite viability. The RM and SI values of the PB-treated group decreased at a more rapid rate than the TCZ-treated group. For NEJs, the decreased RM values were first observed at 1h incubation with 1?g/ml PB, and 90% of flukes were killed at 24h. In contrast, in TCZ-treated groups a 10-fold higher concentration of TCZ (10?g/ml) resulted in only 9% dead parasites after 24h incubation. In 4-weeks-old juvenile parasites, PB reduced the RM value at 10?g/ml with 100% of flukes dead after 3h, while TCZ decreased RM values at the concentration of 100?g/ml but with only 5% of flukes killed at 24h. NEJs treated with PB exhibited 88%, 99% and 100% of LMIs at the concentrations of 1, 10 and 100?g/ml, respectively. NEJs incubated with TCZ have an LMI of only 32% at the highest concentration of 100?g/ml. Similarly PB had a significantly greater killing of immature 4weeks juvenile stages than TCZ at all concentrations; however, 4-weeks-old juvenile parasites were more resistant to killing by PB or TCZ at all concentrations when compared to NEJs. Further studies were carried out to investigate the alterations of the parasite tegument by scanning electron microscope (SEM). PB caused similar tegumental alterations in 4-weeks-old juveniles as those observed in TCZ treatment but with greater damage at comparative time points, comprising of swelling, blebbing and rupture of the tegument, loss of spines, and eventual erosion, lesion and desquamation of the total tegument. These data indicate that PB had a greater fasciolicidal effect against immature stages of F. gigantica parasites than TCZ and warrant further studies for use as a potential new anthelmintic against Fasciola infections. PMID:24157317

Lorsuwannarat, Natcha; Piedrafita, David; Chantree, Pathanin; Sansri, Veerawat; Songkoomkrong, Sineenart; Bantuchai, Sirasate; Sangpairot, Kant; Kueakhai, Pornanan; Changklungmoa, Narin; Chaichanasak, Pannigan; Chansela, Piyachat; Sobhon, Prasert

2014-01-01

257

Recent acquisitions on chemotherapy and chemoprophylaxis of malaria.  

PubMed

The most recent acquisitions on chemotherapy and chemoprophylaxis of malaria are reviewed. With regard to chemotherapy, candidate antimalarial compounds have been divided into four groups, according to their stages of development. Mefloquine and the combination of mefloquine with sulfadoxine/pyrimethamine belong to the first group: they have completed clinical trials and have been registered in several countries for routine clinical use. The second group is characterized by chemical compounds which are in an advanced stage of development, including clinical trials. The compounds considered in this group are: a) the 9-phenanthrenemethanols, among which halofantrine is the most promising one; b) the sesquiterpene lactones such as Qinghaosu, artemether, artesunate, artesunic acid and arteether which must be further tested in order to find more effective drug regimens capable of eliminating recrudescences and for the completion of toxicity studies; c) pyronaridine, which appears to be a promising antimalarial, effective also against chloroquine-resistant P. falciparum, but still requiring further investigations on resistance and cross-resistance, as well as its pharmacokinetics, tolerability and bioavailability; d) enpiroline, another promising compound, which needs to be further studied in Phase II and Phase III investigations with naturally acquired malaria. The third group is composed of seven chemical classes of compounds that are in an advanced pre-clinical development, namely: the 4-aminoquinolines, such as dabechin, piperaquine, hydroxypiperaquine, tripiperaquine, dichlor-quinazine and the Mannich base compounds, the 8-aminoquinolines, the 4-quinolinemethanols, the quinolones, the naphthoquinones, the quinazolines and the dihydrotriazines. Among the many antimalarial compounds of interest, which can be considered at the moment as leads for further studies, only the acridandione derivatives such as floxacrine, the antibiotics, antifungal agents or their metabolites, plant substances such as Yingzhaosu A and quassinoids have been mentioned. Malaria chemoprophylaxis, especially in chloroquine-resistant P. falciparum areas, has become a real problem. The attempts to secure protection under these circumstances with the utilization of amodiaquine, the combination of sulfadoxine/pyrimethamine (Fansidar), sulfalene/pyrimethamine (Metakelfin), of pyrimethamine/dapsone (Maloprim), with or without chloroquine, had to be abandoned or to be used with caution in view of the severe complications following the weekly administration of these drugs. The combination of chloroquine with proguanil or chlorproguanil, which could be recommended on theoretical bases, did not meet the expectations when tested in the field. (ABSTRACT TRUNCATED AT 400 WORDS) PMID:2698608

Onori, E; Majori, G

1989-01-01

258

Naphthalene distributions and human exposure in Southern California  

NASA Astrophysics Data System (ADS)

The regional distribution of, and human exposure to, naphthalene are investigated for Southern California. A comprehensive approach is taken in which advanced models are linked for the first time to quantify population exposure to the emissions of naphthalene throughout Southern California. Naphthalene is the simplest and most abundant of the polycyclic aromatic hydrocarbons found in polluted urban environments, and has been detected in both outdoor and indoor air samples. Exposure to high concentrations of naphthalene may have adverse health effects, possibly causing cancer in humans. Among the significant emission sources are volatilization from naphthalene-containing products, petroleum refining, and combustion of fossil fuels and wood. Gasoline and diesel engine exhaust, with related vaporization from fuels, are found to contribute roughly half of the daily total naphthalene burden in Southern California. As part of this study, the emission inventory for naphthalene has been verified against new field measurements of the naphthalene-to-benzene ratio in a busy traffic tunnel in Los Angeles, supporting the modeling work carried out here. The Surface Meteorology and Ozone Generation (SMOG) airshed model is used to compute the spatial and temporal distributions of naphthalene and its photooxidation products in Southern California. The present simulations reveal a high degree of spatial variability in the concentrations of naphthalene-related species, with large diurnal and seasonal variations as well. Peak naphthalene concentrations are estimated to occur in the early morning hours in the winter season. The naphthalene concentration estimates obtained from the SMOG model are employed in the Regional Human Exposure (REHEX) model to calculate population exposure statistics. Results show average hourly naphthalene exposures in Southern California under summer and winter conditions of 270 and 430 ng m -3, respectively. Exposure to significantly higher concentrations may occur for individuals close to local sources, or in naphthalene "hotspots" revealed by simulations and observations. Such levels of naphthalene exposure may be used to gauge the potential health impacts of long-term naphthalene exposure. Results are also given for the distributions of 1,4-naphthoquinone, a naphthalene reaction product that may have significant health effects.

Lu, Rong; Wu, Jun; Turco, Richard P.; Winer, Arthur M.; Atkinson, Roger; Arey, Janet; Paulson, Suzanne E.; Lurmann, Fred W.; Miguel, Antonio H.; Eiguren-Fernandez, Arantzazu

259

Affinity and activity of non-native quinones at the Q(B) site of bacterial photosynthetic reaction centers.  

PubMed

Purple, photosynthetic reaction centers from Rhodobacter sphaeroides bacteria use ubiquinone (UQ10) as both primary (Q(A)) and secondary (Q(B)) electron acceptors. Many quinones reconstitute Q(A) function, while a few will act as Q(B). Nine quinones were tested for their ability to bind and reconstitute Q(A) and Q(B) functions. Only ubiquinone (UQ) reconstitutes both functions in the same protein. The affinities of the non-native quinones for the Q(B) site were determined by a competitive inhibition assay. The affinities of benzoquinones, naphthoquinone (NQ), and 2-methyl-NQ for the Q(B) site are 7 ± 3 times weaker than that at Q(A) site. However, di-ortho-substituted NQs and anthraquinone bind tightly to the Q(A) site (K d ? 200 nM), and ?1,000 times more weakly to the Q(B) site, perhaps setting a limit on the size of the site. With a low-potential electron donor, 2-methyl, 3-dimethylamino-1,4-NQ, (Me-diMeAm-NQ) at Q(A), Q(B) reduction is 260 meV, more favorable than with UQ as Q(A). Electron transfer from Me-diMeAm-NQ at the Q(A) site to NQ at the Q(B) site can be detected. In the Q(B) site, the NQ semiquinone is estimated to be ?60-100 meV higher in energy than the UQ semiquinone, while in the Q(A) site, the semiquinone energy level is similar or lower with NQ than with UQ. Thus, the NQ semiquinone is more stable in the Q(A) than in the Q(B) site. In contrast, the native UQ semiquinone is ?60 meV lower in energy in the Q(B) than in the Q(A) site, stabilizing forward electron transfer from Q(A) to Q(B). PMID:23715773

Zhang, Xinyu; Gunner, M R

2014-05-01

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Plumbagin attenuates cancer cell growth and osteoclast formation in the bone microenvironment of mice  

PubMed Central

Aim: To investigate the effects of plumbagin, a naphthoquinone derived from the medicinal plant Plumbago zeylanica, on human breast cancer cell growth and the cancer cell-induced osteolysis in the bone microenvironment of mice. Methods: Human breast cancer cell subline MDA-MB-231SA with the ability to spread and grow in the bone was tested. The cell proliferation was determined using the CCK-8 assay. Apoptosis was detected with Annexin V/PI double-labeled flow cytometry. Red fluorescent protein-labeled MDA-MB-231SArfp cells were injected into the right tibia of female BALB/c-nu/nu mice. Three days after the inoculation, the mice were injected with plumbagin (2, 4, or 6 mg/kg, ip) 5 times per week for 7 weeks. The growth of the tumor cells was monitored using an in vivo imaging system. After the mice were sacrificed, the hind limbs were removed for radiographic and histological analyses. Results: Plumbagin (2.5–20 ?mol/L) concentration-dependently inhibited the cell viability and induced apoptosis of MDA-MB-231SA cells in vitro (the IC50 value of inhibition of cell viability was 14.7 ?mol/L). Administration of plumbagin to breast cancer bearing mice delayed the tumor growth by 2–3 weeks and reduced the tumor volume by 44%–74%. The in vivo imaging study showed that plumbagin dose-dependently inhibited MDA-MB-231SArfp cell growth in bone microenvironment. Furthermore, X-ray images and micro-CT study demonstrated that plumbagin reduced bone erosion area and prevented a decrease in bone tissue volume. Histological studies showed that plumbagin dose-dependently inhibited the breast cancer cell growth, enhanced the cell apoptosis and reduced the number of TRAcP-positive osteoclasts. Conclusion: Plumbagin inhibits the cell growth and induces apoptosis in human breast cancer cells in mice bone microenvironment, leading to significant reduction in osteolytic lesions caused by the tumor cells. PMID:24384612

Yan, Wei; Wang, Ting-yu; Fan, Qi-ming; Du, Lin; Xu, Jia-ke; Zhai, Zan-jing; Li, Hao-wei; Tang, Ting-ting

2014-01-01