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1

Naphthoquinone Antibiotics from 'Fusarium solani'.  

National Technical Information Service (NTIS)

The invention relates to new naphthoquinone derivatives which exhibit antibiotic activity. Three naphthoquinones isolated from cultures of Fusarium solani were found to be effective antibiotics against gram-positive bacteria. Controlling the dissolved oxy...

R. A. Baker J. H. Tatum

1988-01-01

2

Inhibition of topoisomerase I by naphthoquinone derivatives  

Microsoft Academic Search

Alkannin and shikonin are naturally occurring naphthoquinones. We have tested several derivatives of the title compounds and we have found that naphthoquinones bearing at least one phenolic hydroxyl group are potent inhibitors of topoisomerase I. The ability of the tested compounds to complex Zn++ parallels with a few exceptions their topoisomerase I inhibition properties while their intercalation and redox properties

Zoi F. Plyta; Tianhu Li; Vassilios P. Papageorgiou; Antonios S. Mellidis; Andreana N. Assimopoulou; Emmanuel N. Pitsinos; Elias A. Couladouros

1998-01-01

3

A new dimeric naphthoquinone from Diospyros anisandra.  

PubMed

From the hexane extract of stem bark of Diospyros anisandra was isolated a new plumbagin dimer, epoxide of zeylanone, along with 14 known compounds, including seven naphthoquinones, four triterpenoids and three sesquiterpenoids. The structures were elucidated by the application of IR, UV, MS, 1D- and 2D-NMR spectroscopic analysis and by comparison with literature data. PMID:22963268

Uc-Cachón, A H; Molina-Salinas, G M; Said-Fernández, S; Méndez-González, M; Cáceres-Farfán, M; Borges-Argáez, R

2013-01-01

4

Reviews on 1,4-naphthoquinones from Diospyros L.  

PubMed

The genus Diospyros is one of the most important sources of bioactive compounds, exclusively 1,4-naphthoquinones. The following information is an attempt to cover the developments in the biology and phytochemistry of 1,4-naphthoquinones isolated from this genus, as well as the studies done and the suggested mechanisms regarding their activities. During the past 60 years, many of these agents have been isolated from Diospyros L. Twelve considerable bioactive structures are reported in this review. The basic 1,4-naphthoquinone skeletons, on which a large number of studies have been done, are plumbagin and diospyrin. Today, the potential for development of leads from 1,4-naphthoquinones obtained from Diospyros L. is growing dramatically, mainly in the area of anticancer and antibacterial investigations. The data prepared and described here are intended to be served as a reference tool to the natural products and chemistry specialists in order to expand the rational drug design. PMID:22263598

Nematollahi, Alireza; Aminimoghadamfarouj, Noushin; Wiart, Christophe

2012-01-01

5

New naphthoquinone from the root of Lygodium japonicum (Thunb.) Sw.  

PubMed

A new 1,4-naphthoquinone and three known compounds were isolated from the roots of Lygodium japonicum (Thunb.) Sw. The structure of the new compound was elucidated by two-dimensional nuclear magnetic resonance and other spectral examinations. PMID:20091244

Chen, Lijuan; Zhang, Guogang; He, Jie; Guan, Jin; Pan, Chunyuan; Mi, Wenzhen; Wang, Qing

2010-01-01

6

New naphthoquinone from the root of Lygodium japonicum (Thunb.) Sw  

Microsoft Academic Search

A new 1,4-naphthoquinone and three known compounds were isolated from the roots of Lygodium japonicum (Thunb.) Sw. The structure of the new compound was elucidated by two-dimensional nuclear magnetic resonance and other spectral\\u000a examinations.

Lijuan Chen; Guogang Zhang; Jie He; Jin Guan; Chunyuan Pan; Wenzhen Mi; Qing Wang

2010-01-01

7

5'-monohydroxyphylloquinone is the dominant naphthoquinone of PSI in the green alga Chlamydomonas reinhardtii.  

PubMed

Thylakoid membranes contain two types of quinones, benzoquinone (plastoquinone) and naphthoquinone, which are involved in photosynthetic electron transfer. Unlike the benzoquinone, the chemical species of naphthoquinone present (phylloquinone, menaquinone-4 and 5'-monohydroxyphylloquinone) varies depending on the oxygenic photosynthetic organisms. The green alga Chlamydomonas reinhardtii has been used as a model organism to study the function of the naphthoquinone bound to PSI. However, the level of phylloquinone and the presence of other naphthoquinones in this organism remain unknown. In the present study, we found that 5'-monohydroxyphylloquinone is the predominant naphthoquinone in cell and thylakoid extracts based on the retention time during reverse phase HPLC, absorption and mass spectrometry measurements. It was shown that 5'-monohydroxyphylloquinone is enriched 2.5-fold in the PSI complex as compared with thylakoid membranes but that it is absent from PSI-deficient mutant cells. We also found a small amount of phylloquinone in the cells and in the PSI complex and estimated that accumulated 5'-monohydroxyphylloquinone and phylloquinone account for approximately 90 and 10%, respectively, of the total naphthoquinone content. The ratio of these two naphthoquinones remained nearly constant in the cells and in the PSI complexes from logarithmic and stationary cell growth stages. We conclude that both 5'-monohydroxyphylloquinone and phylloquinone stably co-exist as major and minor naphthoquinones in Chlamydomonas PSI. PMID:22138100

Ozawa, Shin-ichiro; Kosugi, Makiko; Kashino, Yasuhiro; Sugimura, Takashi; Takahashi, Yuichiro

2012-01-01

8

Biomimetic synthesis of zeylanone and zeylanone epoxide by dimerization of 2-methyl-1,4-naphthoquinone.  

PubMed

A biomimetic synthesis of zeylanone and zeylanone epoxide, which are natural dimeric naphthoquinones, has been accomplished starting from plumbagin, a natural monomeric naphthoquinone. The key features of our synthesis are cascade intermolecular and intramolecular Michael reactions, followed by epoxidation of the resultant hydroquinone with molecular oxygen. PMID:23527796

Maruo, Sayako; Nishio, Kazuyuki; Sasamori, Takahiro; Tokitoh, Norihiro; Kuramochi, Kouji; Tsubaki, Kazunori

2013-04-01

9

Antimutagenic and antioxidant properties of plumbagin and other naphthoquinones.  

PubMed

The structure-function relationships of the naphthoquinone phytochemicals, plumbagin, juglone, and menadione, have been studied with regard to antimutagenic and antioxidant activities. Antimutagenicity of these compounds was assessed by the Ames test and RNA polymerase B (rpoB)-based rifampicin resistance assay. Antioxidant potential was evaluated by radical scavenging assays and reducing power measurement. Protection of cells and DNA against gamma radiation-induced oxidative damage was assayed by survival analysis and gel electrophoresis profiling, respectively. On the 1,4-naphthoquinone nucleus, plumbagin possesses 5-hydroxyl and 2-methyl functional groups, whereas juglone has only the 5-hydroxyl and menadione only the 2-methyl group. Plumbagin showed strong antimutagenic (against ultraviolet and ethyl methanesulfonate) and antioxidant activities, whereas juglone displayed only strong antimutagenic, and menadione only strong antioxidant activities. Thus, these two functional groups (5-OH/2-CH3) play important roles in the differential bioactivity of naphthoquinones. Escherichia coli, microarray analysis showed upregulation of the genes rep (replication/repair), ybaK (tRNA editing), speE (spermidine synthesis), and yjfC (glutathionyl spermidine synthesis) by plumbagin or juglone, and sodC (superoxide dismutase), xthA (oxidative repair), hycB (electron carrier between hydrogenase 3 and fumarate dehydrogenase), and ligA (formation of phosphodiester bond in DNA) by plumbagin or menadione. Studies with E. coli single-gene knockouts showed that ybaK and speE, reported to prevent mistranslation, are likely to be involved in the antimutagenicity displayed by juglone, and sodC to be involved in the antioxidant activity of menadione. PMID:23688616

Kumar, Sanjeev; Gautam, Satyendra; Sharma, Arun

2013-07-01

10

Radiative and nonradiative processes in naphthoquinone vapors at low pressure  

NASA Astrophysics Data System (ADS)

Emission and excitation spectra and emission lifetimes have been investigated for 1,4-naphthoquinone (NQ) and 2-methyl-1,4-naphthoquinone (MNQ) vapors at low pressure (10-3-10-1 Torr). The vapors emit prompt fluorescence from the S1(n, ?*) state in addition to the phosphorescence and E-type delayed fluorescence. In the case of excitation into the S2(?, ?*) state, the quantum yield of the prompt fluorescence increases as the pressure is lowered, whereas the phosphorescence quantum yield decreases down to zero. For both NQ and MNQ vapors, the phosphorescence quantum yield shows characteristic excitation-energy dependence: the yield varies markedly according to the nature of the singlet state to which the molecule is initially excited. On the basis of the pressure and excitation-energy dependence of the emission quantum yields and lifetimes, the occurrence of the prompt fluorescence is interpreted in terms of a mechanism involving reversible intersystem crossing between S1 and a triplet state. It is shown that the prompt fluorescence consists of fast and slow components.

Itoh, Takao; Baba, Hiroaki

1980-09-01

11

Coproduction and ecological significance of naphthoquinones in carnivorous sundews (Drosera).  

PubMed

While the 1,4-naphthoquinone derivatives 7-methyljuglone (1) and plumbagin (2) possess a diverse and well documented array of biological activities, relatively little remains known about the functional significance of these compounds in planta and, in particular, their possible relation to carnivorous syndromes. In addition, the chemotaxonomic distribution of naphthoquinones (NQs) amongst species of Drosera L. is of phytopharmaceutical interest. Following the quantitative assessment of interspecific variation of 1 and 2 in 13 species and cultivars of Drosera, our findings demonstrate that these NQs are ubiquitously coproduced in, generally, species-specific ratios, and that 1 appears negatively associated with the occurrence of pigmentation in sundews. The prospective antifeedant function of 1 was evaluated in relation to allocation in various organs and ontogenetic phases of D. capensis L., revealing that significantly higher levels were accumulated in young and reproductive organs, most likely for defensive purposes. Investigation into the relationship between the biosynthesis of NQs and carnivory showed that production of 1 is optimally induced and localized in leaves in response to capture of insect prey. As a whole, these findings reveal the clear importance of this secondary metabolite in ecological interactions as well as holding implication for future bioactivity studies on the genus. PMID:22700223

Egan, Paul A; van der Kooy, Frank

2012-06-01

12

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

13

Enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes catalyzed by binaphthyl-derived organocatalysts  

PubMed Central

Summary The highly enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes, promoted by binaphthyl-modified chiral bifunctional organocatalysts is described. This reaction afforded the chiral functionalized naphthoquinones in high yields (81–95%) and excellent enantioselectivities (91–98% ee) under low catalyst loading (1 mol %).

Woo, Saet Byeol

2012-01-01

14

Synthesis and evaluation of Hsp90 inhibitors that contain the 1,4-naphthoquinone scaffold  

PubMed Central

High-throughput screening of a library of diverse molecules has identified the 1,4-naphthoquinone scaffold as a new class of Hsp90 inhibitors. The synthesis and evaluation of a rationally–designed series of analogues containing the naphthoquinone core scaffold has provided key structure–activity relationships for these compounds. The most active inhibitors exhibited potent in vitro activity with low micromolar IC50 values in anti-proliferation and Her2 degradation assays. In addition, 3g, 12, and 13a induced the degradation of oncogenic Hsp90 client proteins, a hallmark of Hsp90 inhibition. The identification of these naphthoquinones as Hsp90 inhibitors provides a new scaffold upon which improved Hsp90 inhibitors can be developed.

Hadden, M. Kyle; Hill, Stephanie A.; Davenport, Jason; Matts, Robert L.; Blagg, Brian S. J.

2009-01-01

15

THz spectra of 1,4-naphthoquinones and its four derivatives  

NASA Astrophysics Data System (ADS)

Recently some naphthoquinone derivatives have been found with anticancer or other therapeutic properties, but also have some negative side effects. Numerous research projects have been conducted to investigate their properties and therapeutic mechanisms. With Terahertz Time-Domain Spectroscopy (THz-TDS), we have successfully obtained THz spectra of 1,4-naphthoquinone and its four derivatives in a series of naphthazarin - juglone - 1,4-naphthoquinone - menadione - plumbagin, in the range between 0.2 and 2.4~2.8 THz. Although these molecules are almost identical to each other, they have very distinctive THz spectra so that they can be identified much more easily than using conventional spectroscopy. We have comparatively analyzed their THz spectra, and found some possible correlations between THz spectra and molecular structures. These THz spectra cannot only be used as spectral fingerprint, but also provide us their conformational properties that can be used in study of their interaction with biomolecules to reveal their pharmaceutical mechanisms.

Wang, Weining; Li, Hongqi; Luo, Xiang; Zeng, Xiaoni

2008-03-01

16

Thiourea-catalyzed Diels-Alder reaction of a naphthoquinone monoketal dienophile  

PubMed Central

Summary A variety of organocatalysts were screened for the catalysis of the naphthoquinone monoketal Diels–Alder reaction. In this study we found that Schreiner's thiourea catalyst 10 and Jacobson's thiourea catalyst 12 facilitate the cycloaddition of the sterically hindered naphthoquinone monoketal dienophile 3 with diene 4. The use of thiourea catalysis allowed for the first time the highly selective synthesis of the exo-product 2a in up to 63% yield. In this reaction a new quaternary center was built. The so formed cycloaddition product 2a represents the ABC tricycle of beticolin 0 (1) and is also a valuable model substrate for the total synthesis of related natural products.

Kramer, Carsten S

2013-01-01

17

?-Lapachone: a naphthoquinone with promising antischistosomal properties in mice.  

PubMed

The activity of ?-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione, ?-lap) against different stages of Schistosoma mansoni was investigated in mice. Mice infected with 50 cercariae (BH strain) were intraperitoneally treated at a dose of 50 mg/kg for 5 consecutive days, starting on the 1st, 14th, 28th and 45th days after infection, to evaluate the effect of ?-lap on skin schistosomula, lung schistosomula, young worms (before oviposition) and adult worms (after oviposition), respectively. All animals were euthanized 60 days after infection. ?-Lap significantly reduced (p<0.001) the number of worms in 29.78%, 37.2%, 24.2% and 40.22% when administered during the phases of skin schistosomula, lung schistosomula, young worms and adult worms, respectively. Significant reduction was also achieved in terms of female burden. In all groups, there was significant reduction in the number of eggs and granulomas in the hepatic tissue. When the intervention was performed during the phase of adult worms, ?-lap reduced the size of hepatic granulomas and changed the oogram pattern, lowering the percentage of immature eggs and increasing the percentage of mature and dead eggs. Our data indicate that ?-lap has moderate antischistosomal properties. Its molecule may also be used as a prototype for synthesis of new naphthoquinone derivatives with potential schistosomicidal properties. Further studies with different formulations containing ?-lap are needed to clearly establish the best dose and route of administration and its mechanism of action against schistosomes. PMID:24090700

Aires, André de Lima; Ximenes, Eulália Camelo Pessoa Azevedo; Barbosa, Vanessa Xavier; Góes, Alexandre José da Silva; Souza, Valdênia Maria Oliveira; Albuquerque, Mônica Camelo Pessôa de Azevedo

2014-02-15

18

Effects and mode of action of 1,4-naphthoquinones isolated from Calceolaria sessilis on tumoral cells and Trypanosoma parasites.  

PubMed

The naphthoquinones 2-hydroxy-3-(1,1-dimethylallyl)-1,4-naphthoquinone (CS-1), (-)-2,3,3-trimethyl-2-3-dihydronaphtho[2,3-b]furan-4,9-quinone (CS-3), and 2-acetoxy-3-(1,1-dimethylallyl)-1,4-naphthoquinone (CS-5) isolated from Calceolaria sessilis were tested against Trypanosoma cruzi epimastigotes, the TA3 tumor cell line and the methotrexate-resistant subline TA3-MTX-R. Naphthoquinone CS-3 was the most active; the 50% culture growth inhibition (I50) on T. cruzi (Tulahuén and LQ strain and DM28c clone) was at concentrations ranging from 2.1 to 5.2 mumolar. Also CS-3 inhibited TA3 and TA3-MTX-R culture growth with an I50 of 2.1 and 3.8 mumolar, respectively. Naphthoquinone CS-3 inhibited the respiration of the tumor cells by interfering with the electron transport at some point between NADH and ubiquinone. The respiration of T. cruzi was not inhibited by naphthoquinone CS-3. Naphthoquinone CS-3 produced a temporary increase of oxygen consumption in T. cruzi and tumor cells, suggesting the generation and participation of free radicals. PMID:8788584

Morello, A; Pavani, M; Garbarino, J A; Chamy, M C; Frey, C; Mancilla, J; Guerrero, A; Repetto, Y; Ferreira, J

1995-10-01

19

Diffusion of 2-methyl-1,4-naphthoquinone (1); carbon dioxide (2)  

NASA Astrophysics Data System (ADS)

This document is part of Subvolume A `Gases in Gases, Liquids and their Mixtures' of Volume 15 `Diffusion in Gases, Liquids and Electrolytes' of Landolt-Börnstein Group IV `Physical Chemistry'. It is part of the chapter of the chapter `Diffusion in Pure Gases' and contains data on diffusion of (1) 2-methyl-1,4-naphthoquinone; (2) carbon dioxide

Winkelmann, J.

20

Diffusion of 2-methyl-1,4-naphthoquinone (1); carbon dioxide (2); hexane (3)  

NASA Astrophysics Data System (ADS)

This document is part of Subvolume A `Gases in Gases, Liquids and their Mixtures' of Volume 15 `Diffusion in Gases, Liquids and Electrolytes' of Landolt-Börnstein Group IV `Physical Chemistry'. It is part of the chapter of the chapter `Diffusion in Pure Gases' and contains data on diffusion of (1) 2-methyl-1,4-naphthoquinone; (2) carbon dioxide; (3) hexane

Winkelmann, J.

21

Spectral and structural characterization of 2-(fluorophenylamino)- and 2-(nitrophenylamino)-1,4-naphthoquinone derivatives  

NASA Astrophysics Data System (ADS)

Naphthoquinone amino derivatives exhibit interesting physicochemical properties and are of interest for potential medicinal purposes. The preparation of novel 2-(nitrophenylamino)-1,4-naphthoquinones derivatives was achieved by reaction of nitroanilines with 1,4-naphthoquinone with a catalytic amount of FeCl3 or by direct nitration of 2-(phenylamino)-1,4-naphthoquinone (PAN). Structural and photophysical properties of a series of NO2PANs and FPANs derivatives are examined using computational and spectroscopic methods. Absorbance and emission spectra are measured in a range of solvent environments to examine the impact of solvent-solute interactions. Additionally quantum calculations are used to evaluate the electronic nature of the spectral transitions and compare structures of the different PAN derivatives. The lowest energy electronic transitions have charge transfer character, and show the most sensitivity to solvent and substituents. Higher energy ?-?* transitions are relatively insensitive to both factors. Computational predictions are in good agreement with the experimental spectra, and provide molecular-level insight variations amongst the different aniline-substituents.

Leyva, Elisa; Schmidtke Sobeck, Sarah J.; Loredo-Carrillo, Silvia E.; Magaldi-Lara, Diego A.

2014-06-01

22

Extension of Lifespan in C. elegans by Naphthoquinones That Act through Stress Hormesis Mechanisms  

PubMed Central

Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C. elegans cap‘n’collar (CNC) transcription factor, SKN-1, mediates protective responses to oxidative stress. Genetic analysis showed that skn-1 activity is required for lifespan extension by low-dose plumbagin in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.

Wilson, Mark A.; Yu, Quian-Sheng; Wood, William H.; Zhang, Yongqing; Becker, Kevin G.; Greig, Nigel H.; Mattson, Mark P.; Camandola, Simonetta; Wolkow, Catherine A.

2011-01-01

23

Study on thermal crosslinking reaction of o-naphthoquinone diazides and application to electrodeposition positive photoresist  

Microsoft Academic Search

The thermal reactions of o-naphthoquinone diazide (NQD) compounds as a material for photoresists were studied in comparison with their photochemical reactions. An NQD compound decomposed at around 140°C and further reacted in the presence of an alcohol in the solution to yield an indenecarboxylic ester. The photochemical reaction of the NQD compound with alcohol also provided the same ester in

Kenji Miyagawa; Keisuke Naruse; Shinsuke Ohnishi; Koji Yamaguchi; Kenji Seko; Nobushige Numa; Naozumi Iwasawa

2001-01-01

24

Antioxidant property of polyhydroxylated naphthoquinone pigments from shells of purple sea urchin Anthocidaris crassispina  

Microsoft Academic Search

Sea urchin gonads are highly priced sushi foodstuff “Uni” in Japanese traditional food, but after removal of them the residual shells with spines are dumped as waste. However, sea urchin shells contain naphthoquinone pigments with several phenolic hydroxyl groups, which were expected to act as potent antioxidant substances by donating hydrogens. Our previous study has evaluated their antioxidant ability to

Rui Kuwahara; Hideo Hatate; Tamami Yuki; Hisashi Murata; Ryusuke Tanaka; Yoichiro Hama

2009-01-01

25

Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms.  

PubMed

Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C. elegans cap'n'collar (CNC) transcription factor, SKN-1, mediates protective responses to oxidative stress. Genetic analysis showed that skn-1 activity is required for lifespan extension by low-dose plumbagin in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway. PMID:21765926

Hunt, Piper R; Son, Tae Gen; Wilson, Mark A; Yu, Quian-Sheng; Wood, William H; Zhang, Yongqing; Becker, Kevin G; Greig, Nigel H; Mattson, Mark P; Camandola, Simonetta; Wolkow, Catherine A

2011-01-01

26

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

PubMed

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. PMID:23774738

Pushpam, S; Kottaisamy, M; Ramakrishnan, V

2013-10-01

27

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

28

Cytotoxicity of naphthoquinones and their capacity to generate reactive oxygen species is quenched when conjugated with gold nanoparticles.  

PubMed

Several reports have demonstrated the anticancer activities of plumbagin, a naphthoquinone derivative isolated from plants belonging to Plumbaginaceae family. However, to the best of our knowledge, there are no reports which describe gold nanoconjugation with plumbagin, even though plumbagin is considered to be a promising therapeutic agent. In this report, we demonstrate the fabrication and characterization of gold nanoparticles conjugated with plumbagin (AuPB) that can reduce the toxicity of the latter, and their capacity for cellular localization and generation of reactive oxygen species. The anticancer activity and ability of plumbagin to produce reactive oxygen species was studied and compared with that of bromoderivatives of 1,4 naphthoquinones such as 2-bromo-1,4-naphthoquinone (2-BNQ) and 2,3-dibromo-1, 4-naphthoquinone (2,3-DBNQ) and their gold nanoconjugates. Plumbagin and bromoderivatives of 1,4 naphthoquinones in the form of gold nanoconjugates showed reduced cytotoxicity and apoptosis compared with the pristine compounds, ie, plumbagin, 2-BNQ, and 2,3-DBNQ. Interestingly, we observed that the gold nanoparticles could quench the reactive oxygen species-generating capacity of plumbagin, 2-BNQ, and 2,3-BNQ, which is one of the main mechanisms of action of the naphthoquinones. Therefore, it can be concluded that conjugation with gold nanoparticles can reduce the cytotoxicity of these compounds. PMID:22114475

Srinivas, Priya; Patra, Chitta Ranjan; Bhattacharya, Santanu; Mukhopadhyay, Debabrata

2011-01-01

29

The Study of Naphthoquinones and Their Complexes with DNA by Using Raman Spectroscopy and Surface Enhanced Raman Spectroscopy: New Insight into Interactions of DNA with Plant Secondary Metabolites  

PubMed Central

Naphthoquinones represent the group of plant secondary metabolites with cytotoxic properties based on their ability to generate reactive oxygen species and interfere with the processes of cell respiration. Due to this fact, the possible cytotoxic mechanisms on cellular and subcellular levels are investigated intensively. There are many targets of cytotoxic action on the cellular level; however, DNA is a critical target of many cytotoxic compounds. Due to the cytotoxic properties of naphthoquinones, it is necessary to study the processes of naphthoquinones, DNA interactions (1,4-naphthoquinone, binapthoquinone, juglone, lawsone, plumbagin), especially by using modern analytical techniques. In our work, the Raman spectroscopy was used to determine the possible binding sites of the naphthoquinones on the DNA and to characterize the bond of naphthoquinone to DNA. Experimental data reveals the relationships between the perturbations of structure-sensitive Raman bands and the types of the naphthoquinones involved. The modification of DNA by the studied naphthoquinones leads to the nonspecific interaction, which causes the transition of B-DNA into A-DNA conformation. The change of the B-conformation of DNA for all measured DNA modified by naphthoquinones except plumbagin is obvious.

Vrana, Oldrich; Adam, Vojtech

2014-01-01

30

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.

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

31

Anticancer activity and SAR studies of substituted 1,4-naphthoquinones.  

PubMed

In this paper, we report the structure-activity relationship studies of substituted 1,4-naphthoquinones for its anticancer properties. 1,4-Naphthoquinone, Juglone, Menadione, Plumbagin and LLL12.1 were used as lead molecules to design PD compounds. Most of the PD compounds showed improved antiproliferative activity in comparison to the lead molecule in prostate (DU-145), breast (MDA-MB-231) and colon (HT-29) cancer cell lines. PD9, PD10, PD11, PD13, PD14 and PD15 were found to be the most potent compound with an IC? value of 1-3 ?M in all cancer cell lines. Fluorescent polarization assay was employed to study the inhibition of STAT3 dimerization by PD compounds. PD9 and PD18 were found to be potent STAT3 dimerization inhibitors. PMID:23791367

Bhasin, Deepak; Chettiar, Somsundaram N; Etter, Jonathan P; Mok, May; Li, Pui-Kai

2013-08-01

32

Antitrypanosomal activities and cytotoxicity of some novel imido-substituted 1,4-naphthoquinone derivatives.  

PubMed

The antitrypanosomal activities, cytotoxicity, and selectivity indices of eleven imido-substituted 1,4-naphthoquinone derivatives and nifurtimox have been studied. Compared to nifurtimox (IC(50) = 10.67 ?M), all the imido-naphthoquinone analogs (IMDNQ1-IMDNQ11) are more potent on Trypanosoma cruzi with IC50 values ranging from 0.7 ?M to 6.1 ?M (p < 0.05). Studies of the cytotoxic activities of these compounds on a Balb/C 3T3 mouse fibroblast cell line revealed that four of these compounds, IMDNQ1, IMDNQ2, IMDNQ3, and IMDNQ10 displayed selectivity indices of 60.25, 53.97, 31.83, and 275.3, respectively, rendering them significantly (p < 0.05) more selective in inhibiting the parasite growth than nifurtimox (selectivity index = 10.86). PMID:22297740

Khraiwesh, Mozna H; Lee, Clarence M; Brandy, Yakini; Akinboye, Emmanuel S; Berhe, Solomon; Gittens, Genelle; Abbas, Muneer M; Ampy, Franklin R; Ashraf, Mohammad; Bakare, Oladapo

2012-01-01

33

Naphthoquinone contents of in vitro cultured plants and cell suspensions of Dionaea muscipula and Drosera species  

Microsoft Academic Search

In vitro cultured carnivorous plants were grown on a hormone-free medium. They produced the following naphthoquinones: Dionaea muscipula (plumbagin: 5.3%), Drosera rotundifolia (7-methyljuglone: 0.6%), D. binata (plumbagin: 1.4%), and D. capensis (7-methyljuglone: 0.5%). A red, slow-growing suspension culture of D. muscipula was maintained in a modified McCowns Woody Plant (McC) medium and produced plumbagin (2.59%) after 30 days growth. A

Ingrid L. I. Hook

2001-01-01

34

Synthesis and biological activity against Trypanosoma cruzi of substituted 1,4-naphthoquinones.  

PubMed

The discovery and development of essential drugs for Chagas disease is a major concern worldwide. New substituted 1,4-naphthoquinones were synthesized and tested against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. These products exhibited substantial activity against T. cruzi, especially 2-((8E,11Z)-heptadeca-8,11-dienyl)-3-hydroxynaphthalene-1,4-dione (9) with IC(50) of 7.8 ?M. PMID:23279867

Olímpio da Silva, Adriano; da Silva Lopes, Rosangela; Vieira de Lima, Ricardo; Santos Suniga Tozatti, Camila; Marques, Maria Rita; de Albuquerque, Sérgio; Beatriz, Adilson; Pires de Lima, Dênis

2013-02-01

35

Electron transfer in DNA duplexes containing 2-methyl-1,4-naphthoquinone  

Microsoft Academic Search

Methyl-1,4-naphthoquinone (menadione, MQ) was linked to synthetic oligonucleotides and exposed to near-UV light to generate base radical cations in DNA. This model system of electron transfer induced alkali- labile breaks at GG doublets, similar to anthraquinone and metallointercalators systems. In sharp contrast to other systems, the photolysis of MQ-DNA duplexes gave interstrand cross-links and alkali-labile breaks at bases on the

Francois Bergeron; Daniel Houde; Darel J. Hunting; J. Richard Wagner

2004-01-01

36

Stereoselective synthesis and cytotoxicity of a cancer chemopreventive naphthoquinone from Tabebuia avellanedae.  

PubMed

Stereoselective synthesis of 1, one of biologically active naphthoquinones from a Brazilian traditional medicine Tabebuia avellanedae, was achieved by utilizing Noyori reduction as a key step. Compound 1 displayed potent cytotoxicity against several human tumor cell lines, whereas it showed lower cytotoxicity against some human normal cell lines compared with that of mitomycin. On the other hand, its enantiomer was less active toward the tumor cell lines than 1. PMID:17950604

Yamashita, Mitsuaki; Kaneko, Masafumi; Iida, Akira; Tokuda, Harukuni; Nishimura, Katsumi

2007-12-01

37

EDA Complexes of 2,3-Dichloro-1,4-naphthoquinone with Some Substituted Anilines  

Microsoft Academic Search

Summary. Electron donor-acceptor (EDA) complexes of several substituted anilines with the p-acceptor 2,3-dichloro-1,4-naphthoquinone ( DCl NQ) in chloroform, dichloromethane, and 1,2-dichloroethane were studied by a spectrophotometric method. Experimental data has been shown to confirm the 1:2 stoichiometry of the acceptor-donor in spite of the apparent linearity of the Benesi-Hildebrand plot for a 1:1 complex. The calculated values of oscillator strengths,

Gururaj M. Neelgund; Abhay S. Kulkarni; M. L. Budni

2004-01-01

38

Teratomas of Drosera capensis var. alba as a source of naphthoquinone: ramentaceone  

Microsoft Academic Search

Plants belonging to genus Drosera (family Droseraceae) contain pharmacologically active naphthoquinones such as ramentaceone and plumbagin. Hairy root cultures\\u000a obtained following Agrobacterium rhizogenes-mediated transformation have been reported to produce elevated levels of secondary compounds as well as exhibit desirable\\u000a rapid biomass accumulation in comparison to untransformed plants. The aim of this study was to establish hairy root or teratoma\\u000a cultures

Aleksandra Krolicka; Anna Szpitter; Krzysztof Stawujak; Rafal Baranski; Anna Gwizdek-Wisniewska; Anita Skrzypczak; Marian Kaminski; Ewa Lojkowska

2010-01-01

39

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.

2014-01-01

40

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

41

Using of liquid chromatography coupled with diode array detector for determination of naphthoquinones in plants and for investigation of influence of pH of cultivation medium on content of plumbagin in Dionaea muscipula  

Microsoft Academic Search

The interest of many investigators in naphthoquinones is due to their broad-range of biological actions from phytotoxic to fungicidal. The main aim of this work was to investigate the influence of different pH values of cultivation medium on naphthoquinone content in Dionaea muscipula. For this purpose, we optimized the simultaneous analysis of the most commonly occurring naphthoquinones (1,4-naphthoquinone, lawsone, juglone

Petr Babula; Radka Mikelova; Vojtech Adam; Rene Kizek; Ladislav Havel; Zdenek Sladky

2006-01-01

42

Synthesis and biological evaluation of 1,4-naphthoquinones and quinoline-5,8-diones as antimalarial and schistosomicidal agents.  

PubMed

Improving the solubility of polysubstituted 1,4-naphthoquinone derivatives was achieved by introducing nitrogen in two different positions of the naphthoquinone core, at C-5 and at C-8 of menadione through a two-step, straightforward synthesis based on the regioselective hetero-Diels-Alder reaction. The antimalarial and the antischistosomal activities of these polysubstituted aza-1,4-naphthoquinone derivatives were evaluated and led to the selection of distinct compounds for antimalarial versus antischistosomal action. The Ag(II)-assisted oxidative radical decarboxylation of the phenyl acetic acids using AgNO(3) and ammonium peroxodisulfate was modified to generate the 3-picolinyl-menadione with improved pharmacokinetic parameters, high antimalarial effects and capacity to inhibit the formation of ?-hematin. PMID:22777178

Lanfranchi, Don Antoine; Cesar-Rodo, Elena; Bertrand, Benoît; Huang, Hsin-Hung; Day, Latasha; Johann, Laure; Elhabiri, Mourad; Becker, Katja; Williams, David L; Davioud-Charvet, Elisabeth

2012-08-21

43

Synthesis and Biological Evaluation of 1,4-Naphthoquinones and Quinoline-5,8-diones as Antimalarial and Schistosomicidal Agents  

PubMed Central

Improving the solubility of polysubstituted 1,4-naphthoquinone derivatives was achieved by introducing nitrogen in two different positions of the naphthoquinone core, at C-5 and at C-8 of menadione through a two-step, straightforward synthesis based on the regioselective hetero-Diels-Alder reaction. The antimalarial and the antischistosomal activities of these polysubstituted aza-1,4-naphthoquinone derivatives were evaluated and led to the selection of distinct compounds for antimalarial versus antischistosomal action. The AgII-assisted oxidative radical decarboxylation of the phenyl acetic acids using AgNO3 and ammonium peroxodisulfate was modified to generate the 3-picolinyl-menadione with improved pharmacokinetic parameters, high antimalarial effects and capacity to inhibit the formation of ?-hematin.

Lanfranchi, Don Antoine; Cesar-Rodo, Elena; Bertrand, Benoit; Huang, Hsin-Hung; Day, Latasha; Johann, Laure; Elhabiri, Mourad; Becker, Katja; Williams, David L.

2012-01-01

44

Ellagic acid derivatives and naphthoquinones of Dionaea muscipula from in vitro cultures  

Microsoft Academic Search

From Dionaea muscipula, obtained by in vitro culture, the known compounds plumbagin, chloroplumbagin and 8,8?-biplumbagin as naphthoquinones, 1-O-?-galloylglucose, ellagic acid, 3-O-methylellagic acid, 3,3?-di-O-methylellagic acid and its 4-O-glucoside, and a new compound, the 4,4?-di-O-glucoside of 3,3?-di-O-methylellagic acid, were isolated. The assignments of NMR resonances of 3,3?-di-O-methylellagic acid 4-O-glucoside were substantiated by correlation techniques.

Grzegorz Pakulski; Jaromir Budzianowski

1996-01-01

45

In vitro cultures of Drosera aliciae as a source of a cytotoxic naphthoquinone: ramentaceone.  

PubMed

A protocol for the in vitro propagation of Drosera aliciae to increase the yield of the naphthoquinone, ramentaceone, was developed. The highest micropropagation coefficient was obtained using half-strength Murashige-Skoog medium supplemented with 0.4 ?M 6-benzyladenine (BA). The genetic fidelity and stability of the regenerated plants was confirmed with RAPD markers. The activity of the isolated ramentaceone was determined against four human tumor cell lines: U937, HeLa, MCF-7, HCT-116 with the highest cytotoxic activity towards the leukemic U937 cell line with an IC(50) value of 3.2 ?M. PMID:21761256

Kawiak, Anna; Królicka, Aleksandra; ?ojkowska, Ewa

2011-11-01

46

Two New Cytotoxic Naphthoquinones from Mendoncia cowanii from the Rainforest of Madagascar  

PubMed Central

Bioassay-guided fractionation of the root and stem extracts of Mendoncia cowanii led to the isolation of two new and two known naphthoquinones. The structures of the new compounds, avicequinones D and E (1 and 2), were determined using 1D and 2D NMR spectroscopy and by chemical conversion of compound 1 to 2. The new compounds were active in the A2780 human ovarian cancer cell line with IC50 values of 7.4 - 50 ?M, respectively, and 1, 3, and 4 were subsequently found to be weakly active in an assay for inhibition of the kinase Akt.

Williams, Russell B.; Norris, Andrew; Miller, James S.; Razafitsalama, L. Jeremie; Andriantsiferana, Rabodo; Rasamison, Vincent E.; Kingston, David G. I.

2010-01-01

47

Synthesis and evaluation of bioactive naphthoquinones from the Brazilian medicinal plant, Tabebuia avellanedae  

Microsoft Academic Search

A series of naphthoquinones based on the naphtho[2,3-b]furan-4,9-dione skeleton such as (?)-5-hydroxy-2-(1?-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (1) and its positional isomer, (?)-8-hydroxy-2-(1?-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (2), which are secondary metabolites found in the inner bark of Tabebuia avellanedae, were stereoselectively synthesized and their biological activities were evaluated in conjunction with those of their corresponding enantiomers. Compound 1 exhibited potent antiproliferative effect against several human tumor cell lines,

Mitsuaki Yamashita; Masafumi Kaneko; Harukuni Tokuda; Katsumi Nishimura; Yuko Kumeda; Akira Iida

2009-01-01

48

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.

2012-01-01

49

Naphthoquinone derivatives and lignans from the Paraguayan crude drug "tayï pytá" (Tabebuia heptaphylla, Bignoniaceae).  

PubMed

The Paraguayan crude drug "tayï pytá" is used to treat cancer, wounds and inflammation. It consist of the bark and trunkwood of Tabebuia heptaphylla (Bignoniaceae). A phytochemical study of the crude drug gave, in addition to previously described naphthoquinones and the known lignans cycloolivil and secoisolariciresinol, three new lapachenol (lapachonone)-, two naphthofuran-, a chromone and a naphthalene derivative. The structures were elucidated by means of high field NMR spectroscopy. The biological activity of the main compound lapachol and the related alpha-lapachone as well as the lignans cycloolivil and secoisolariciresinol can explain, at least in part, the effect atributed to the crude drug in Paraguayan folk medicine. PMID:12939034

Schmeda-Hirschmann, Guillermo; Papastergiou, Fani

2003-01-01

50

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

51

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

52

Electrochemical strategy to scout 1,4-naphthoquinones effect on voltage gated potassium channels.  

PubMed

Naphthoquinone (NQ) was tested on voltage-gated ion channels expressed in Xenopus laevis oocytes. The activity of potassium Shaker channel with Inactivation domain Removed (ShIR) was not affected; in contrast, NQ diminished Kv1.3 currents. A current decrease was barely observed with the oxidant H(2)O(2). These findings suggested that redox properties were involved in the naphthoquinone-Kv1.3 channel interaction. NQ and some derivatives (NQs) were characterized in DMSO and physiological (ND-96) media by cyclic voltammetry. A typical two-stage mono-electronic reduction mechanism was observed in DMSO, while a one-stage bi-electronic reduction process was found in ND-96 medium. NQs with the lowest and the highest redox potential values were tested on both channels. Voltage-clamp recordings showed that inhibition of Kv1.3 was dependent on NQs redox potential. Results demonstrated that structural features (aromaticity and substituents prone to hydrogen bonds formation) of NQs were also important. This effect could be explained by interactions of some channel residues with NQs that contribute to favor their reduction process in the protein surroundings. The electrochemical strategy presented to simulate the cellular environments (aqueous and non-aqueous) that NQs may face, is an important contribution to pre-select (in a fine and simple way) the best redox compounds for electrophysiological testing. PMID:22265102

Rodríguez-Fernández, T; Ugalde-Saldívar, V M; González, I; Escobar, L I; García-Valdés, J

2012-08-01

53

Insight into naphthoquinone metabolism: beta-glucosidase-catalysed hydrolysis of hydrojuglone beta-D-glucopyranoside.  

PubMed

In plants, the naphthoquinone juglone is known to be involved in pathogenic defence mechanisms, but it may also take part in plant developmental processes. This naphthoquinone can accumulate in a glycosylated form, namely hydrojuglone beta-d-glucopyranoside. The structural configuration of this compound was shown to be 1, 5-dihydroxy-4-naphthalenyl-beta-d-glucopyranoside by means of MS, NMR and nuclear Overhauser effect spectroscopy analyses. A hydrojuglone beta-d-glucopyranoside beta-glucosidase (EC 3.2.1.21) was purified to homogeneity from Juglans regia L. The enzyme catalysed the release of juglone from hydrojuglone beta-d-glucopyranoside with high specificity and showed Michaelis-Menten kinetics with Km=0.62 mM and Vmax=14.5 microkat/mg of protein. This enzyme also showed a higher activity towards beta-d-fucosyl than beta-d-glucosyl bonds. The purified enzyme had an apparent Mr of 64000 by SDS/PAGE and a pI 8.9 by isoelectrofocusing PAGE. The purified enzyme was inhibited by several bivalent cations, such as Cu2+, Fe2+, Hg2+, and by d-glucono-1,5-lactone, showing non-competitive inhibition of the mixed type. PMID:9657966

Duroux, L; Delmotte, F M; Lancelin, J M; Kéravis, G; Jay-Allemand, C

1998-07-15

54

Insight into naphthoquinone metabolism: beta-glucosidase-catalysed hydrolysis of hydrojuglone beta-D-glucopyranoside.  

PubMed Central

In plants, the naphthoquinone juglone is known to be involved in pathogenic defence mechanisms, but it may also take part in plant developmental processes. This naphthoquinone can accumulate in a glycosylated form, namely hydrojuglone beta-d-glucopyranoside. The structural configuration of this compound was shown to be 1, 5-dihydroxy-4-naphthalenyl-beta-d-glucopyranoside by means of MS, NMR and nuclear Overhauser effect spectroscopy analyses. A hydrojuglone beta-d-glucopyranoside beta-glucosidase (EC 3.2.1.21) was purified to homogeneity from Juglans regia L. The enzyme catalysed the release of juglone from hydrojuglone beta-d-glucopyranoside with high specificity and showed Michaelis-Menten kinetics with Km=0.62 mM and Vmax=14.5 microkat/mg of protein. This enzyme also showed a higher activity towards beta-d-fucosyl than beta-d-glucosyl bonds. The purified enzyme had an apparent Mr of 64000 by SDS/PAGE and a pI 8.9 by isoelectrofocusing PAGE. The purified enzyme was inhibited by several bivalent cations, such as Cu2+, Fe2+, Hg2+, and by d-glucono-1,5-lactone, showing non-competitive inhibition of the mixed type.

Duroux, L; Delmotte, F M; Lancelin, J M; Keravis, G; Jay-Allemand, C

1998-01-01

55

Inhibitory Potential of Naphthoquinones Leached from Leaves and Exuded from Roots of the Invasive Plant Impatiens glandulifera.  

PubMed

Exploring the effects of allelopathic plant chemicals on the growth of native vegetation is essential to understand their ecological roles and importance in exotic plant invasion. Naphthoquinones have been identified as potential growth inhibitors produced by Impatiens glandulifera, an exotic annual plant that recently invaded temperate forests in Europe. However, naphthoquinone release and inhibitory potential have not been examined. We quantified the naphthoquinone content in cotyledons, leaves, stems, and roots from plants of different ages of both the invasive I. glandulifera and native Impatiens noli-tangere as well as in soil extracts and rainwater rinsed from leaves of either plant species by using ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS). We identified the compound 2-methoxy-1,4-naphthoquinone (2-MNQ) exclusively in plant organs of I. glandulifera, in resin bags buried into the soil of patches invaded by I. glandulifera, and in rainwater rinsed from its leaves. This indicates that 2-MNQ is released from the roots of I. glandulifera and leached from its leaves by rain. Specific bioassays using aqueous shoot and root extracts revealed a strong inhibitory effect on the germination of two native forest herbs and on the mycelium growth of three ectomycorrhiza fungi. These findings suggest that the release of 2-MNQ may contribute to the invasion success of I. glandulifera and support the novel weapons hypothesis. PMID:24722883

Ruckli, Regina; Hesse, Katharina; Glauser, Gaetan; Rusterholz, Hans-Peter; Baur, Bruno

2014-04-01

56

Is nitric oxide decrease observed with naphthoquinones in LPS stimulated RAW 264.7 macrophages a beneficial property?  

PubMed

The search of new anti-inflammatory drugs has been a current preoccupation, due to the need of effective drugs, with less adverse reactions than those used nowadays. Several naphthoquinones (plumbagin, naphthazarin, juglone, menadione, diosquinone and 1,4-naphthoquinone), plus p-hydroquinone and p-benzoquinone were evaluated for their ability to cause a reduction of nitric oxide (NO) production, when RAW 264.7 macrophages were stimulated with lipopolysaccharide (LPS). Dexamethasone was used as positive control. Among the tested compounds, diosquinone was the only one that caused a NO reduction with statistical importance and without cytotoxicity: an IC(25) of 1.09±0.24 µM was found, with 38.25±6.50% (p<0.001) NO reduction at 1.5 µM. In order to elucidate if this NO decrease resulted from the interference of diosquinone with cellular defence mechanisms against LPS or to its conversion into peroxynitrite, by reaction with superoxide radical formed by naphthoquinones redox cycling, 3-nitrotyrosine and superoxide determination was also performed. None of these parameters showed significant changes relative to control. Furthermore, diosquinone caused a decrease in the pro-inflammatory cytokines: tumour necrosis factor-alpha (TNF-?) and interleukin 6 (IL-6). Therefore, according to the results obtained, diosquinone, studied for its anti-inflammatory potential for the first time herein, has beneficial effects in inflammation control. This study enlightens the mechanisms of action of naphthoquinones in inflammatory models, by checking for the first time the contribution of oxidative stress generated by naphthoquinones to NO reduction. PMID:21887376

Pinho, Brígida R; Sousa, Carla; Valentão, Patrícia; Andrade, Paula B

2011-01-01

57

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

Microsoft Academic Search

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

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

1999-01-01

58

QSAR on antiproliferative naphthoquinones based on a conformation-independent approach.  

PubMed

The antiproliferative activities of a series of 36 naphthoquinone derivatives were subjected to a Quantitative Structure-Activity Relationships (QSAR) study. For this purpose a panel of four human cancer cell lines was used, namely HBL-100 (breast), HeLa (cervix), SW-1573 (non-small cell lung) and WiDr (colon). A conformation-independent representation of the chemical structure was established in order to avoid leading with the scarce experimental information on X-ray crystal structure of the drug interaction. The 1179 theoretical descriptors derived with E-Dragon and Recon software were simultaneously analyzed through linear regression models based on the Replacement Method variable subset selection technique. The established models were validated and tested through the use of external test sets of compounds, the Leave-One-Out Cross Validation method, Y-Randomization and Applicability Domain analysis. PMID:24631897

Duchowicz, Pablo R; Bennardi, Daniel O; Bacelo, Daniel E; Bonifazi, Evelyn L; Rios-Luci, Carla; Padrón, José M; Burton, Gerardo; Misico, Rosana I

2014-04-22

59

Activities and Conformational Fitting of 1,4-Naphthoquinone Derivatives and Other Cyclic 1,4-Diones Tested In Vitro against Pneumocystis carinii  

PubMed Central

Atovaquone is a chemotherapeutic agent used to treat pneumonia caused by Pneumocystis carinii in some immunocompromised patients. A set of cyclic 1,4-diones were tested in vitro for ability to inhibit growth of P. carinii, including 22 variously substituted 1,4-naphthoquinones, one bis-1,4-naphthoquinone, and three other quinones. For comparison, the antipneumocystic primaquine and its 5-hydroxy-6-desmethyl metabolite were also tested. At 1.0 ?g/ml, seven compounds inhibited growth by at least 39%, with atovaquone at 92%; of these seven, five are 2-hydroxy-1,4-naphthoquinones, while one is a 2-chloro- and another is a 2-methyl-1,4-naphthoquinone. At 0.1 ?g/ml, however, the most active compound tested was the primaquine metabolite, which inhibited growth by more than 42% at this concentration. To ascertain a structure-activity relationship, all 1,4-naphthoquinones were compared conformationally by means of computer-based molecular modeling (Spartan) incorporating the Sybyl force field. Without exception, for all 21 monomers tested, the substituent at position 3 of the 1,4-naphthoquinone favored activity most strongly when it simultaneously occupied (i) space centered at about 3 Å from position 3, without projecting steric bulk from the area encompassed by atovaquone's cyclohexyl ring, and (ii) roughly planar space at about 7.3 Å from position 3, without projecting steric bulk perpendicularly. This structure-activity relationship may prove useful in the rational design of better antipneumocystis agents.

Ball, M. D.; Bartlett, M. S.; Shaw, M.; Smith, J. W.; Nasr, M.; Meshnick, S. R.

2001-01-01

60

Cytotoxicity Mechanism of Two Naphthoquinones (Menadione and Plumbagin) in Saccharomyces cerevisiae  

PubMed Central

Background Quinones are compounds extensively used in studies of oxidative stress due to their role in plants as chemicals for defense. These compounds are of great interest for pharmacologists and scientists, in general, because several cancer chemotherapeutic agents contain the quinone nucleus. However, due to differences in structures and diverse pharmacological effects, the exact toxicity mechanisms exerted by quinones are far from elucidatation. Methodology/Principal Findings Using Saccharomyces cerevisiae, we evaluated the main mechanisms of toxicity of two naphthoquinones, menadione and plumbagin, by determining tolerance and oxidative stress biomarkers such as GSH and GSSG, lipid peroxidation levels, as well as aconitase activity. The importance of glutathione transferases (GST) in quinone detoxification was also addressed. The GSSG/GSH ratio showed that menadione seemed to exert its toxicity mainly through the generation of ROS while plumbagin acted as an electrophile reacting with GSH. However, the results showed that, even by different pathways, both drugs were capable of generating oxidative stress through their toxic effects. Our results showed that the control strain, BY4741, and the glutathione transferase deficient strains (gtt1? and gtt2?) were sensitive to both compounds. With respect to the role of GST isoforms in cellular protection against quinone toxicity, we observed that the Gtt2 deficient strain was unable to overcome lipid peroxidation, even after a plumbagin pre-treatment, indicating that this treatment did not improve tolerance when compared with the wild type strain. Cross-tolerance experiments confirmed distinct cytotoxicity mechanisms for these naphthoquinones since only a pre-treatment with menadione was able to induce acquisition of tolerance against stress with plumbagin. Conclusions/Significance These results suggest different responses to menadione and plumbagin which could be due to the fact that these compounds use different mechanisms to exert their toxicity. In addition, the Gtt2 isoform seemed to act as a general protective factor involved in quinone detoxification.

Castro, Frederico Augusto Vieira; Mariani, Diana; Panek, Anita Dolly; Eleutherio, Elis Cristina Araujo; Pereira, Marcos Dias

2008-01-01

61

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

62

Naphthoquinone Derivatives Exert Their Antitrypanosomal Activity via a Multi-Target Mechanism  

PubMed Central

Background and Methodology Recently, we reported on a new class of naphthoquinone derivatives showing a promising anti-trypanosomatid profile in cell-based experiments. The lead of this series (B6, 2-phenoxy-1,4-naphthoquinone) showed an ED50 of 80 nM against Trypanosoma brucei rhodesiense, and a selectivity index of 74 with respect to mammalian cells. A multitarget profile for this compound is easily conceivable, because quinones, as natural products, serve plants as potent defense chemicals with an intrinsic multifunctional mechanism of action. To disclose such a multitarget profile of B6, we exploited a chemical proteomics approach. Principal Findings A functionalized congener of B6 was immobilized on a solid matrix and used to isolate target proteins from Trypanosoma brucei lysates. Mass analysis delivered two enzymes, i.e. glycosomal glycerol kinase and glycosomal glyceraldehyde-3-phosphate dehydrogenase, as potential molecular targets for B6. Both enzymes were recombinantly expressed and purified, and used for chemical validation. Indeed, B6 was able to inhibit both enzymes with IC50 values in the micromolar range. The multifunctional profile was further characterized in experiments using permeabilized Trypanosoma brucei cells and mitochondrial cell fractions. It turned out that B6 was also able to generate oxygen radicals, a mechanism that may additionally contribute to its observed potent trypanocidal activity. Conclusions and Significance Overall, B6 showed a multitarget mechanism of action, which provides a molecular explanation of its promising anti-trypanosomatid activity. Furthermore, the forward chemical genetics approach here applied may be viable in the molecular characterization of novel multitarget ligands.

Mazet, Muriel; Perozzo, Remo; Bergamini, Christian; Prati, Federica; Fato, Romana; Lenaz, Giorgio; Capranico, Giovanni; Brun, Reto; Bakker, Barbara M.; Michels, Paul A. M.; Scapozza, Leonardo; Bolognesi, Maria Laura; Cavalli, Andrea

2013-01-01

63

Reagentless amperometric detection of l-lactate on an enzyme-modified conducting copolymer poly(5-hydroxy-1,4-naphthoquinone-co-5-hydroxy-3-thioacetic acid-1,4-naphthoquinone).  

PubMed

We have constructed a reagentless lactate sensor using lactate oxidase (LOD) covalently attached to an electropolymerized copolymer film, poly(5-hydroxy-1,4-naphthoquinone-co-5-hydroxy-3-thioacetic acid-1,4-naphthoquinone), poly(JUG-co-JUGA). Around 10(-12)Mcm(-2) of covalently bound enzymes are immobilized on these films. In aerated medium, the amperometric response versus lactate concentration shows a sensitivity of 350 +/- 50 microAM(-1)cm(-2) for an applied potential of +0.5V versus Ag|AgCl on a film-coated Pt electrode. In deaerated medium, the quinone group, conjugated with the polymer backbone, acts as an immobilized mediator. An amperometric response is observed on film-coated glassy carbon (GC) electrode at a potential as low as -0.1V versus Ag|AgCl, with a sensitivity of 110 +/- 40 microAM(-1)cm(-2). PMID:15046766

Haccoun, J; Piro, B; Tran, L D; Dang, L A; Pham, M C

2004-05-15

64

Application of the atoms in molecules theory and computational chemistry in mass spectrometry analysis of 1,4-naphthoquinone derivatives.  

PubMed

Mass spectrometry analysis of 2-(acylamino)-1,4-naphthoquinone derivatives was carried out using electrospray ionization ion source in combination with tandem mass spectrometry. Protonated molecules were dissociated by application of the collision-induced dissociation (CID), and the protonation sites were suggested on the basis of the HOMO, molecular electrostatic potential map (MEP), proton affinity, and Fukui functions calculated by B3LYP/6-31+G(d,p). The main fragmentation mechanisms undergone by the protonated ions were elucidated on the basis of energy, geometry, and topology analysis of equilibrium geometries. Compounds exhibiting only aliphatic hydrogens at the lateral chain undergo interesting ketene elimination. On the other hand, only the benzoylium ion formation is detected for 2-benzoylamino-1,4-naphthoquinone. The bonds geometric and atoms in molecules parameters give evidence that acidic hydrogen atoms play an important role in the fragmentation pathways. PMID:21714561

Vessecchi, Ricardo; Lopes, José N C; Lopes, Norberto P; Galembeck, Sérgio E

2011-11-17

65

In vitro activity of Brazilian medicinal plants, naturally occurring naphthoquinones and their analogues, against methicillin-resistant Staphylococcus aureus.  

PubMed

Fourteen extracts from Brazilian traditional medicinal plants used to treat infectious diseases were used to look for potential antimicrobial activity against multiresistant bacteria of medical importance. Staphylococcus aureus strains were susceptible to extracts of Punica granatum and Tabebuia avellanedae. The minimum inhibitory concentrations (MICs) of the total extracts and of additional fractions of these plants were determined by employing strains of methicillin-resistant (MRSA) and -sensitive (MSSA) S. aureus, including isolates of the PFGE clone A, which is prevalent in Brazil and two ATCC reference strains. A mixture of ellagitannins isolated from P. granatum and two naphthoquinones isolated from T. avellanedae demonstrated antibacterial activity against all S. aureus strains tested. Semi-synthetic furanonaphthoquinones (FNQs) showed lower MICs than those exhibited by natural occurring naphthoquinones. The results indicate that these natural products can be effective potential candidates for the development of new strategies to treat MRSA infections. PMID:12636992

Machado, T B; Pinto, A V; Pinto, M C F R; Leal, I C R; Silva, M G; Amaral, A C F; Kuster, R M; Netto-dosSantos, K R

2003-03-01

66

An assessment of the genotoxicity of 2-hydroxy-1,4-naphthoquinone, the natural dye ingredient of Henna  

Microsoft Academic Search

2-Hydroxy-1,4-naphthoquinone (HNQ; Lawsone; CAS 83-72-7) is the principal natural dye ingredient contained in the leaves of Henna (Lawsonia inermis). Published genotoxicity studies on HNQ suggested it was a weak bacterial mutagen for Salmonella typhimurium strain TA98 or was more clearly mutagenic for strain TA 2637, both in the presence of metabolic activation. HNQ was unable to induce sex-linked recessive lethal

David Kirkland; Daniel Marzin

2003-01-01

67

Effects of 2-methyl-1,4-naphthoquinone (menadione) on myocardial contractility and cardiac sarcoplasmic reticulum Ca-ATPase  

Microsoft Academic Search

(1) In electrically driven guinea-pig left atria, menadione (2-methyl-1,4-naphthoquinone) (1 to 20 µmol\\/1) and menadione sodium bisulfate (30 to 200 µmol\\/1) produced marked positive inotropic effects. Endogenously released catecholamines and histamine contributed to 80–85% of the effect, the residual 15–20% appearing as a direct effect. (2) In electrically driven guinea-pig ventricular strips, low micromolar concentrations of menadione (0.05 to 0.3

M. Floreani; E. Santa Soncin; F. Carpenedo

1989-01-01

68

Effects of 1,4-naphthoquinone on aluminum corrosion in 0.50 M sodium chloride solutions  

Microsoft Academic Search

Effects of 1,4-naphthoquinone (NQ) have been investigated as a corrosion inhibitor for aluminum in aerated and de-aerated solutions of 0.50M NaCl using potentiodynamic polarization, chronoamperometry (CA), open-circuit potential (OCP), electrochemical impedance spectroscopic (EIS), scanning electron microscopic (SEM), cyclic voltammetric, and quartz crystal analyzer (QCA) techniques. These measurements revealed that the presence of NQ shifted the corrosion and pitting potentials to

E. M. Sherif; Su-Moon Park

2006-01-01

69

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

70

Photogeneration and reactivity of naphthoquinone methides as purine selective DNA alkylating agents.  

PubMed

A one-step protecting-group-free synthesis of both 6-hydroxy-naphthalene-2-carbaldehyde and the bifunctional binaphthalenyl derivative afforded 6-hydroxymethylnaphthalen-2-ol, 6-methylaminomethyl-naphthalen-2-ol, [(2-hydroxy-3-naphthyl)methyl]trimethyl ammonium iodide, and a small library of bifunctional binol analogues in good yields. Irradiation of naphthol quaternary ammonium salt and binol-derivatives (X = OH, NHR, NMe(3)(+), OCOCH(3), and L-proline) at 310 and 360 nm resulted in the photogeneration of the 2,6-naphthoquinone-6-methide (NQM) and binol quinone methide analogues (BQMs) by a water-mediated excited-state proton transfer (ESPT). The hydration, the mono- and bis-alkylation reactions of morpholine and 2-ethanethiol, as N and S prototype nucleophiles, by the transient NQM (?(max) 310, 330 nm) and BQMs (?(max) 360 nm) were investigated in water by product distribution analysis and laser flash photolysis (LFP). Both the photogeneration and the reactivity of NQM and BQMs exhibited striking differences. BQMs were at least 2 orders of magnitude more reactive than NQM, and they were generated much more efficiently from a greater variety of photoprecursors including the hydroxymethyl, quaternary ammonium salt and several binol-amino acids. On the contrary, the only efficient precursor of NQM was the quaternary ammonium salt. All water-soluble BQM precursors were further investigated for their ability to alkylate and cross-link plasmid DNA and oligonucleotides by gel electrophoresis: the BQMs were more efficient than the isomeric o-BQM (binol quinone methide analogue of 2,3-naphthoquinone-3-methide). Sequence analysis by gel electrophoresis, HPLC, and MS showed that the alkylation occurred at purines, with a preference for guanine. In particular, a BQM was able to alkylate N7 of guanines resulting in depurination at the oligonucleotide level, and ribose loss at the nucleotide level. The photoreactivity of BQM precursors translated into photocytotoxic and cytotoxic effects on two human cancer cell lines: in particular, one compound showed promising selectivity index on both cell lines. PMID:20863115

Verga, Daniela; Nadai, Matteo; Doria, Filippo; Percivalle, Claudia; Di Antonio, Marco; Palumbo, Manlio; Richter, Sara N; Freccero, Mauro

2010-10-20

71

A study on the properties and reactivity of naphthoquinone-cobalt(III) prototypes for bioreductive prodrugs.  

PubMed

Our group has recently initiated a study on the development of new prototypes for bioreductive prodrugs, based on Co(III) complexes with the ligand 2,2'-bis(3-hydroxy-1,4-naphthoquinone), H2bhnq. The focus of this work is to investigate the dissociation of bhnq(-2) from the complex upon reduction, and the effects of pH, redox potential, oxygen concentration and nature of the auxiliary ligands on this reaction. The bhnq(2-) ligand is a "non-cytotoxic" agent that was chosen as a probe for the reactivity studies due to its suitable chromophoric properties, at the same time that it resembles more cytotoxic naphthoquinones relevant for cancer therapy. In this way, two Co(III) complexes [Co(bhnq)(L1)]BF4·H2O (1) and [Co(bhnq)(L2)]BF4·H2O (2) (L1=N,N'-bis(pyridin-2-ylmethyl)ethylenediamine and L2=N,N'-dimethyl-N,N'-bis(pyridin-2-ylmethyl)ethylenediamine) were synthesized and fully characterized. The gallium analogs [Ga(bhnq)(L1)]NO3·3H2O (3) and [Ga(bhnq)(L2)]NO3·3H2O (4) were also prepared for helping with the assignments of the redox properties of the cobalt complexes and the structure of 2. Cyclic voltammetry analysis revealed a pH-independent quasi-reversible Co(III)/Co(II) process at -0.22 and -0.08V vs NHE for 1 and 2, respectively. An O2-dependent dissociation of bhnq(2-) was observed for the reaction of 1 with ascorbic acid. For 2, the dissociation of bhnq(2-) was found to be independent on the concentration of O2 and faster than in 1, with little influence of the pH on both complexes. The difference in reactivity between 1 and 2 and their redox properties, among other factors, suggests that 1 undergoes redox cycling, pointed out as a key feature for a prodrug to achieve hypoxic selectivity. PMID:24326134

Bustamante, Francisco L S; Miranda, Fabio S; Castro, Frederico A V; Resende, Jackson A L C; Pereira, Marcos D; Lanznaster, Mauricio

2014-03-01

72

Design, synthesis, and biological testing of novel naphthoquinones as substrate-based inhibitors of the quinol/fumarate reductase from Wolinella succinogenes.  

PubMed

Novel naphthoquinones were designed, synthesized, and tested as substrate-based inhibitors against the membrane-embedded protein quinol/fumarate reductase (QFR) from Wolinella succinogenes, a target closely related to QFRs from the human pathogens Helicobacter pylori and Campylobacter jejuni. For a better understanding of the hitherto structurally unexplored substrate binding pocket, a structure-activity relationship (SAR) study was carried out. Analogues of lawsone (2-hydroxy-1,4-naphthoquinone 3a) were synthesized that vary in length and size of the alkyl side chains (3b-k). A combined study on the prototropic tautomerism of 2-hydroxy-1,4-naphthoquinones series indicated that the 1,4-tautomer is the more stable and biologically relevant isomer and that the presence of the hydroxyl group is crucial for inhibition. Furthermore, 2-bromine-1,4-naphthoquinone (4a-c) and 2-methoxy-1,4-naphthoquinone (5a-b) series were also discovered as novel and potent inhibitors. Compounds 4a and 4b showed IC50 values in low micromolar range in the primary assay and no activity in the counter DT-diaphorase assay. PMID:24251984

Nasiri, Hamid Reza; Madej, M Gregor; Panisch, Robin; Lafontaine, Michael; Bats, Jan W; Lancaster, C Roy D; Schwalbe, Harald

2013-12-12

73

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

74

Oxidation reactions of hydroxy naphthoquinones: Mechanistic investigation by LC-Q-TOF-MS analysis.  

PubMed

Abstract Purpose: The hydroxyl radical ((?)OH)-induced oxidation reactions of isomeric hydroxy naphthoquinones (generally having anti-tumor activities) namely, lawsone and juglone, were carried out and the reaction mechanism was elucidated. Materials and methods: The degradation products from the reaction of (?)OH (produced by H2O2/UV) with lawsone and juglone were analyzed using a liquid chromatography quadrupole-time-of-flight mass spectrometer (LC-Q-TOF-MS). The transient intermediate studies were investigated using picosecond pulse radiolysis technique. Results: Mono hydroxylated and dihydroxylated adducts of both lawsone and juglone were identified from the product analysis. The isomeric mono-hydroxylated adducts of lawsone were confirmed using survival yield (SY) analysis. The hydroxylated adducts of lawsone also underwent dimerization reaction. The transient spectral analysis using pulse radiolysis studies revealed the formation of hydroxycyclohexadienyl type radical of both lawsone and juglone as the initially formed intermediate. Conclusions: The (?)OH-induced reactions of both lawsone and juglone result in the mono and di-hydoxylated derivatives. The demonstration of the various isomeric products using mass spectrometry is a clear proof of the addition probability of (?)OH at different positions of lawsone and juglone, which is generally a difficult task using other analytical techniques. PMID:24597783

Sreekanth, Radhakrishnan; Menachery, Sunil Paul M; Aravind, Usha K; Marignier, Jean-Louis; Belloni, Jacqueline; Aravindakumar, Charuvila T

2014-06-01

75

[Naphthoquinone antibiotics from Streptomyces lateritius. I Fermentation, isolation and characterization of granatomycins A, C, and D].  

PubMed

The fermentation and isolation procedures of the antibiotic granatomycin produced by Streptomyces lateritius are described. Furthermore, the producing strain ZIMET 43 627 and the main constituents of granatomycin will be characterized. Granatomycin is a red-violet pigment antibiotic of the naphthoquinone type. The physicochemical properties of granatomycin resemble those of granaticin. The antibiotic can be isolated from culture filtrates and from the mycelium by extraction with lower aliphatic alcohols. It can be purified by gel filtration methods. Granatomycin displays antimicrobial activity, particularly against grampositive and gramnegative bacteria, and antiviral activity against fowl-plaque-virus in mammalian cells. Granatomycin is useful in selection of resistant mutants of bacteria and viruses with decreased virulence but high immunogenity suitable for use as life vaccines against infection diseases. The physicochemical properties of the main constituents of granatomycin studied confirm the identity of granatomycin C with granaticin and the identity of granatomycin D with dihydrogranaticin Granatomycin A is identical with the well-known semisynthetic methylester of dihydrogranaticin. Therefore, the production of granatomycin A is the first possibility to produce this derivative of granaticin biosynthetically. PMID:7210705

Fleck, W F; Strauss, D G; Prauser, H

1980-01-01

76

Synthesis and evaluation of bioactive naphthoquinones from the Brazilian medicinal plant, Tabebuia avellanedae.  

PubMed

A series of naphthoquinones based on the naphtho[2,3-b]furan-4,9-dione skeleton such as (-)-5-hydroxy-2-(1'-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (1) and its positional isomer, (-)-8-hydroxy-2-(1'-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (2), which are secondary metabolites found in the inner bark of Tabebuia avellanedae, were stereoselectively synthesized and their biological activities were evaluated in conjunction with those of their corresponding enantiomers. Compound 1 exhibited potent antiproliferative effect against several human tumor cell lines, but its effect against some human normal cell lines was much lower than that of mitomycin. On the other hand, its enantiomer (R)-1 was less active toward the above tumor cell lines than 1. The antiproliferative effect of 2 against all tumor cell lines was significantly reduced. These results indicated the presence of the phenolic hydroxy group at C-5 is of great important for increasing antiproliferative effect. In addition, 1 also showed higher cancer chemopreventive activity than 2, while there were no significant differences between 1 and 2 in antimicrobial activity. Both compounds displayed modest antifungal and antibacterial activity (gram-positive bacteria), whereas they were inactive against gram-negative bacteria. PMID:19674905

Yamashita, Mitsuaki; Kaneko, Masafumi; Tokuda, Harukuni; Nishimura, Katsumi; Kumeda, Yuko; Iida, Akira

2009-09-01

77

Double mode of inhibition-inducing interactions of 1,4-naphthoquinone with urease: arylation versus oxidation of enzyme thiols.  

PubMed

In their inhibition-inducing interactions with enzymes, quinones primarily utilize two mechanisms, arylation and oxidation of enzyme thiol groups. In this work, we investigated the interactions of 1,4-naphthoquinone with urease in an effort to estimate the contribution of the two mechanisms in the enzyme inhibition. Jack bean urease, a homohexamer, contains 15 thiols per enzyme subunit, six accessible under non-denaturing conditions, of which Cys592 proximal to the active site indirectly participates in the enzyme catalysis. Unlike by 1,4-benzoquinone, a thiol arylator, the inactivation of urease by 1,4-naphthoquinone under aerobic conditions was found to be biphasic, time- and concentration-dependent with a non-linear residual activity-modified thiols dependence. DTT protection studies and thiol titration with DTNB suggest that thiols are the sites of enzyme interactions with the quinone. The inactivated enzyme had approximately 40% of its activity restored by excess DTT supporting the presence of sulfenic acid resulting from the oxidation of enzyme thiols by ROS. Furthermore, the aerobic inactivation was prevented in approximately 30% by catalase, proving the involvement of hydrogen peroxide in the process. When H2O2 was directly applied to urease, the enzyme showed susceptibility to this inactivation in a time- and concentration-dependent manner with the inhibition constant of H2O2 Ki = 3.24 mM. Additionally, anaerobic inactivation of urease was performed and was found to be weaker than aerobic. The results obtained are consistent with a double mode of 1,4-naphthoquinone inhibitory action on urease, namely through the arylation of the enzyme thiol groups and ROS generation, notably H2O2, resulting in the oxidation of the groups. PMID:17416528

Krajewska, Barbara; Zaborska, Wies?awa

2007-06-15

78

pH-Dependent rectification in redox polymers: Characterization of electrode-confined siloxane polymers containing naphthoquinone and benzylviologen subunits  

SciTech Connect

This paper describes the electrochemical characterization of electrode-confined siloxane polymers that contain both naphthoquinone (NQ) and benzylviologen (BV{sup 2}{sup +}) subunits. These `homopolymers,` abbreviated (NQ-BV{sup 3+}){sub n} and (NQ-BV-BV{sup 5+}){sub n}, are derived from monomers, 2-chloro-3-[[2-(dimethyl[[[N`-[[4-(trimethoxysilyl)phenyl]methyl]-4, 4`-bipyridiniumyl]methyl]phenyl]methyl]ammonium)-ethyl]amino]-1,4-naphthoquinone, 1a, and 2-chloro-3-[[2-(dimethyl[[[[[[[[N`-[N`-[[4-(trimethoxysilyl)phenyl]methy]-4,4`-bipyridiniumyl]methyl]-phenyl]methyl]-4, 4`-bipyridiniumyl]methyl]phenyl]methyl]ammonium)ethyl]amino]-1,4-naphthoquinone, 2a, respectively. Particular to these types of surface-confined homopolymers is the ability to `trap` charge at low pH in the form of reduced quinone. The flexibility of these monolayers apparently allows direct contact of the NQ subunit with the electrode surface. Less flexible and more robust surface-confined polymers, abbreviated (NQ-BV{sup 3+}/siloxane){sub n} and (NQH{sub 2}-BV-BV{sup 5+}siloxane){sub n}, can be prepared by copolymerization of 1a or 2a with 1,2-bis(trimethoxysilyl)ethane. Charge trapped in (NQH{sub 2}-BV{sup 3+}/siloxane){sub n} or (NQH{sub 2}-BV-BV{sup 5+}/siloxane){sub n} can be released and delivered to the surface of the electrode via chemical mediation or by an increase in solution pH. 26 refs., 13 figs.

Palmore, G.T.R.; Smith, D.K.; Wrighton, M.S. [Massachusetts Institute of Technology, Cambridge, MA (United States)] [Massachusetts Institute of Technology, Cambridge, MA (United States)

1997-04-03

79

Synthesis and Biological Activity of New Thiopyrano[2,3-d]thiazoles Containing a Naphthoquinone Moiety.  

PubMed

Novel 11-substituted 3,11-dihydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]-thiazole-2,5,10-triones 4a-i were synthesized in 75-90% yields via the hetero-Diels-Alder reaction of 5-arylidene-4-thioxo-2-thiazolidinones with 1,4-naphthoquinone. The synthesized compounds were evaluated for their antineoplastic and antimycobacterial activities. A moderate selectivity against melanoma cancer cells (GI50 (UACC-257-melanoma) = 0.22 ?M) was demonstrated for 4i, whereas derivatives 4a, 4c, 4g, and 4h showed promising antimycobacterial activity at a low toxicity level. PMID:23833711

Atamanyuk, Dmytro; Zimenkovsky, Borys; Atamanyuk, Vasyl; Nektegayev, Ihor; Lesyk, Roman

2013-06-01

80

Synthesis and Biological Activity of New Thiopyrano[2,3-d]thiazoles Containing a Naphthoquinone Moiety  

PubMed Central

Novel 11-substituted 3,11-dihydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]-thiazole-2,5,10-triones 4a–i were synthesized in 75–90% yields via the hetero-Diels-Alder reaction of 5-arylidene-4-thioxo-2-thiazolidinones with 1,4-naphthoquinone. The synthesized compounds were evaluated for their antineoplastic and antimycobacterial activities. A moderate selectivity against melanoma cancer cells (GI50 (UACC-257-melanoma) = 0.22 ?M) was demonstrated for 4i, whereas derivatives 4a, 4c, 4g, and 4h showed promising antimycobacterial activity at a low toxicity level.

Atamanyuk, Dmytro; Zimenkovsky, Borys; Atamanyuk, Vasyl; Nektegayev, Ihor; Lesyk, Roman

2013-01-01

81

Bioactivities of simplified adociaquinone B and naphthoquinone derivatives against Cdc25B, MKP-1, and MKP-3 phosphatases.  

PubMed

Some simplified adociaquinone B analogs and a series of 1,4-naphthoquinone derivatives were synthesized and tested against the three enzymes Cdc25B, MKP-1, and MKP-3. Cdc25B and MKP-1 in particular are enzymes overexpressed in human cancer cells, and they represent potential molecular targets for novel cancer chemotherapeutic treatments. A number of analogs exhibited significant inhibitory activity against these enzymes, and the bioassay data in addition to structure-activity relationships of these compounds will be discussed. PMID:19028102

Cao, Shugeng; Murphy, Brian T; Foster, Caleb; Lazo, John S; Kingston, David G I

2009-03-15

82

Bioactivities of Simplified Adociaquinone B and Naphthoquinone Derivatives against Cdc25B, MKP-1, and MKP-3 Phosphatases  

PubMed Central

Some simplified adociaquinone B analogs and a series of 1,4-naphthoquinone derivatives were synthesized and tested against the three enzymes Cdc25B, MKP-1, and MKP-3. Cdc25B and MKP1 in particular are enzymes overexpressed in human cancer cells, and they represent potential molecular targets for novel cancer chemotherapeutic treatments. A number of analogs exhibited significant inhibitory activity against these enzymes, and the bioassay data in addition to structure–activity relationships of these compounds will be discussed.

Cao, Shugeng; Murphy, Brian T.; Foster, Caleb; Lazo, John S.; Kingston, David G. I.

2010-01-01

83

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

84

Nitric Oxide Effect on Naphthoquinone Toxicity in Endothelial Cells: Role of Bioenergetic Dysfunction and PARP Activation  

PubMed Central

When produced at physiological levels reactive oxygen species (ROS) can act as signaling molecules to regulate normal vascular function. Produced under pathological conditions, ROS can contribute to oxidative damage of cellular components (e.g., DNA and proteins) and trigger cell death. Moreover, the reaction of superoxide with nitric oxide (NO) produces the strong oxidant peroxynitrite and decreases NO bioavailability, both of which may contribute to activation of cell death pathways. The effects of ROS generated from the 1,4-naphthoquinones alone and in combination with NO on the activation status of poly(ADP-ribose) polymerase (PARP) and cell viability were examined. Treatment with redox cycling quinones activates PARP, and this stimulatory effect is attenuated in the presence of NO. Mitochondria play a central role in cell death signaling pathways and are a target of oxidants. We show that simultaneous exposure of endothelial cells to NO and ROS results in mitochondrial dysfunction, ATP and NAD+ depletion, and cell death. Alone, NO and ROS have only minor effects on cellular bioenergetics. Further, PARP inhibition does not attenuate reduced cell viability or mitochondrial dysfunction. These results show that concomitant exposure to NO and ROS impairs energy metabolism and triggers PARP-independent cell death. While superoxide-mediated PARP activation is attenuated in the presence of NO, PARP inhibition does not modify the loss of mitochondrial function or adenine and pyridine nucleotide pools and subsequent bioenergetic dysfunction. These findings suggest that the mechanisms by which ROS and NO induce endothelial cell death is closely linked to maintenance of mitochondrial function and not overactivation of PARP.

Broniowska, Katarzyna A.; Diers, Anne R.; Corbett, John A.; Hogg, Neil

2014-01-01

85

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

86

Liquid perfluorodecalin application for in situ extraction and enhanced naphthoquinones production in Arnebia euchroma cell suspension cultures.  

PubMed

Suspension cultures of Arnebia euchroma supported with liquid perfluorodecalin (PFD) degassed, aerated, or ethylene-saturated were investigated as a novel in situ extraction system for enhanced alkannin/shikonin production. Simultaneously, the effect of PFD applied as the liquid gas carrier on the growth of A. euchroma biomass was studied. The similar dry (4-fold) and fresh (7-fold) biomass increase was observed in the control (without PFD addition) and supplemented with PFD-degassed or PFD-aerated cultures while PFD-ethylene application impeded cell growth. The highest total of alkannin/shikonin production (23.23 mg flask(-1)) was observed when PFD-aerated has been used and it resulted in about 50% higher yield of alkannin/shikonin compared with the control culture. Chiral HPLC analysis revealed that in cultures supported with PFD, both alkannin and shikonin were produced. Their mutual ratio varied depending on culture conditions, and the accumulation of alkannin prevailed under almost all culture conditions. PFD has proved to be exceptionally efficient and cell-safe solvent for the in situ extraction of naphthoquinone red pigments without exerting any detrimental effects on cell growth. Extracellularly secreted red naphthoquinones were easily dissolved and extracted from the PFD phase, which can be regenerated and reused (e.g., in continuous culture system). PMID:24420283

Syk?owska-Baranek, Katarzyna; Pilarek, Maciej; Cichosz, Micha?; Pietrosiuk, Agnieszka

2014-03-01

87

Electron donor-acceptor interaction of 3,4-dimethylaniline with 2,3-dicyano-1,4-naphthoquinone.  

PubMed

The electron donor-acceptor (EDA) interaction between 2,3-dicyano-1,4-naphthoquinone (DCNQ) and 3,4-dimethylaniline (3,4-DMA) is studied in chloroform, dichloromethane and 1:1 (v/v) mixture of chloroform and dichloromethane. The rate of formation of the product was measured as a function of time using UV-vis spectrophotometer. The formation constant (K) and molar extinction coefficient (?) values for the formation of EDA complex were evaluated in the temperature range of 20-35°C. The pseudo-first-order rate constant (k1) and the second-order rate constant (k2) for the disappearance of EDA complex and for the formation of product were evaluated. The activation parameters (?H#, ?S# and ?G#) of the reaction were determined by temperature dependence of rate constants using the Arrhenius plots. The effect of relative permittivity of the medium on the reaction is discussed. The observed results indicate that formation of final product proceeds through initial formation of EDA complex as an intermediate. The product of the reaction was purified by column chromatography method and identified as 3-(N-3,4-dimethyl-phenylamino)-2-cyano-1,4-naphthoquinone by elemental analysis, IR and NMR spectroscopy. On the basis of kinetic, analytical and spectroscopic results, a plausible mechanism for the formation of EDA complex and its transformation into product is proposed. PMID:21147022

Neelgund, Gururaj M; Magadum, Subash R; Budni, M L

2011-01-01

88

Electron donor-acceptor interaction of 3,4-dimethylaniline with 2,3-dicyano-1,4-naphthoquinone  

NASA Astrophysics Data System (ADS)

The electron donor-acceptor (EDA) interaction between 2,3-dicyano-1,4-naphthoquinone (DCNQ) and 3,4-dimethylaniline (3,4-DMA) is studied in chloroform, dichloromethane and 1:1 (v/v) mixture of chloroform and dichloromethane. The rate of formation of the product was measured as a function of time using UV-vis spectrophotometer. The formation constant ( K) and molar extinction coefficient ( ?) values for the formation of EDA complex were evaluated in the temperature range of 20-35 °C. The pseudo-first-order rate constant ( k1) and the second-order rate constant ( k2) for the disappearance of EDA complex and for the formation of product were evaluated. The activation parameters (? H#, ? S# and ? G#) of the reaction were determined by temperature dependence of rate constants using the Arrhenius plots. The effect of relative permittivity of the medium on the reaction is discussed. The observed results indicate that formation of final product proceeds through initial formation of EDA complex as an intermediate. The product of the reaction was purified by column chromatography method and identified as 3-( N-3,4-dimethyl-phenylamino)-2-cyano-1,4-naphthoquinone by elemental analysis, IR and NMR spectroscopy. On the basis of kinetic, analytical and spectroscopic results, a plausible mechanism for the formation of EDA complex and its transformation into product is proposed.

Neelgund, Gururaj M.; Magadum, Subash R.; Budni, M. L.

2011-01-01

89

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

90

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

91

Bias-voltage-induced decomposition of 2-methyl-1,4-naphthoquinone on Ag/AlOx/Al tunnel junction  

NASA Astrophysics Data System (ADS)

Bias-voltage-induced decomposition of 2-methyl-1,4-naphthoquinone (MeNQ) dispersed in polystyrene on an Ag/AlOx/Al tunnel junction is examined using IR reflection absorption spectroscopy. Under no bias voltage, IR bands due to MeNQ decrease only slightly. In contrast, when the Ag electrode is biased to -2.8 eV, which corresponds to the electronic absorption edge of MeNQ, the IR bands of MeNQ are significantly decreased in intensity. Bias voltages of +2.8 eV and ±1.5 eV promote the band-intensity reduction less. These results reveal that hot holes with appropriate energies promote the decomposition of MeNQ on the tunnel junction.

Wadayama, T.; Kojim, A.; Hatta, A.

2004-12-01

92

The quenching effect of silver nanoparticles on 2-amino-3-bromo-1, 4-naphthoquinone using fluorescence spectroscopy.  

PubMed

Nanoparticles of noble metals belong to the most extensively studied colloidal systems in the field of nanoscience and nanotechnology. Silver nanoparticles of different sizes have been prepared with the chemical reduction method using sodium borohydride and characterized using optical absorption technique. Using optical absorption and fluorescence emission studies, the photo physical properties of 2-amino-3-bromo1, 4-naphthoquinone (ABNQ) on silver nanoparticle have been studied. Concentration of the silver nanoparticle has been evaluated and the particle size dependent interaction between silver nanoparticles and ABNQ has been studied. The fluorescence quantum yield of ABNQ with and without silver nanoparticles has been calculated. The Stern-Volmer quenching constants and the molar absorptivity have been evaluated. PMID:24252292

Manikandan, P; Pushpam, S; Sasirekha, V; Rani, J Suvetha; Ramakrishnan, V

2014-03-01

93

Synthesis using microwave irradiation and antibacterial evaluation of new N,O-acetals and N,S-acetals derived from 2-amino-1,4-naphthoquinones.  

PubMed

This paper describes a novel series of N,O-acetals and N,S-acetals (7a-o) derived from 2-amino-1,4-naphthoquinones that were synthesized and evaluated as potential antimicrobial agents. These compounds were obtained in good yields using microwave irradiation, and several of them showed promising antibacterial profiles. Three of our biologically active 2-amino-1,4-naphthoquinone N,O-acetals and N,S-acetals tested against hospital bacterial strains were identified as potential lead compounds. Characterization of all compounds was performed using one-dimensional NMR techniques ((1)H, (13)C-APT), IR spectra, elemental analyses and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). PMID:23474905

Jordão, Alessandro K; Novais, Juliana; Leal, Bruno; Escobar, Ana C; dos Santos, Helvécio M; Castro, Helena C; Ferreira, Vitor F

2013-05-01

94

Studies on Charge-Transfer Complexes of 2,3-Dicyano-1,4-naphthoquinone with Some Ring and N -Substituted Anilines  

Microsoft Academic Search

Summary. The charge-transfer complexes (CT-complexes) between 2,3-dicyano-1,4-naphthoquinone ( DCNQ) and some aromatic anilines, both ring and N-substituted, were studied spectrophotometrically in three chlorinated solvents, viz. chloroform, dichloromethane, and 1,2-dichloroethane at different temperatures. All the donors are known to form stable 1:1 stoichiometric complexes with DCNQ and their stoichiometry was unaffected by the variation of temperature over the studied range. The

Gururaj M. Neelgundand; M. L. Budni

2004-01-01

95

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

96

The reduction of 2-bromomethyl-3-methyl- and 2,3-bis-bromomethyl-1,4-naphthoquinones, potential bioreductive alkylating agents. Electrochemical and computational studies  

Microsoft Academic Search

In the present work, 2,3-dimethyl-1,4-naphthoquinones, substituted at one or both side chains with bromine were prepared and submitted to electrochemical studies (cyclic voltammetry and electrolysis), in aprotic medium (DMF+0.1 mol l?1 TBAP), using different electrodes (Hg, GC and Au), to observe the role of bromide, as a good leaving group, in their electroreductions. The cyclic voltammograms are complex. Combined results

Fabiane C de Abreu; Adriana C. O Lopes; Silmar A do Monte; Nivaldo A Soares; Mar??lia O. F Goulart

2003-01-01

97

Mediated electrochemical reduction of oxygen to hydrogen peroxide via a surface-confined naphthoquinone reagent and the mediated electrochemical reduction of a naphthoquinone redox reagent anchored to high surface area oxides  

SciTech Connect

Derivatives of 1,4-naphthoquinone, 2-chloro-3-((2-(dimethylpropylammonio)ethyl)amino)-1,4-naphthoquinone bromide, Ia, and 2-chloro-3-((2-(dimethyl(3-(trimethoxysilyl)propyl)ammonio)ethyl)amino)-1,4-naphthoquinone bromide, Ib, have been synthesized and used as solution and surface-bound catalysts, respectively, for the electrochemical and photoelectrochemical reduction of O/sub 2/ to H/sub 2/O/sub 2/. The surface derivatizing reagent Ib having the -Si(OCH/sub 3/)/sub 3/ functionality can be used to functionalize a variety of surfaces including electrode materials and high surface area oxides. The surface reagent, (Q/QH/sub 2/)/sub surf/, has the same E/sup 0/' as Ia in solution, approx. -0.4 V vs. SCE at pH 7. The (QH/sub 2/)/sub surf/ reacts with O/sub 2/ in aqueous electrolyte at pH 7 with a rate constant > 10/sup 5/ M/sup -1/s/sup -1/ to form H/sub 2/O/sub 2/ and (Q)/sub surf/. High surface area oxides functionalized with Ib yield (M/sub x/O/sub y/)-(Q) that can be electrochemically reduced to (M/sub x/O/sub y/)-(QH/sub 2/) via mediation by a low concentration of Ia in solution. The (M/sub x/O/sub y/)-(QH/sub 2/) can be isolated from the electrolyte solution by filtration and reacted with O/sub 2//H/sub 2/O to yield up to 0.1 M H/sub 2/O/sub 2/ in H/sub 2/O free of electrolyte. Study of the reduction of Ia at rotating-W-disk electrodes derivatized with Ib shows that the redox equilibration of the solution quinone and surface quinone is rapid. Reduction of (Q)/sub surf/ or Ia at visible light illuminated p-WS/sub 2/ can be effected at an electrode potential approx. 0.8 V more positive than at a metallic electode. The overall energetics are such that light can be used to effect the uphill formation of H/sub 2/O/sub 2/ via the quinone-mediated reduction of O/sub 2/. The onset of O/sub 2/ reduction is up to 0.6 V more positive than E/sup 0/'(O/sub 2//H/sub 2/O/sub 2/). The sustained photoassisted reduction of O/sub 2/ to H/sub 2/O/sub 2/ has been demonstrated. 15 references, 8 figures, 2 tables.

Calabrese, G.S.; Buchanan, R.M.; Wrighton, M.S.

1983-08-24

98

Using of liquid chromatography coupled with diode array detector for determination of naphthoquinones in plants and for investigation of influence of pH of cultivation medium on content of plumbagin in Dionaea muscipula.  

PubMed

The interest of many investigators in naphthoquinones is due to their broad-range of biological actions from phytotoxic to fungicidal. The main aim of this work was to investigate the influence of different pH values of cultivation medium on naphthoquinone content in Dionaea muscipula. For this purpose, we optimized the simultaneous analysis of the most commonly occurring naphthoquinones (1,4-naphthoquinone, lawsone, juglone and plumbagin) by high performance liquid chromatography coupled with diode array detector (HPLC-DAD). The most suitable chromatographic conditions were as follows: mobile phase: 0.1 mol l-1 acetic acid:methanol in ratio of 33:67 (%, v/v), flow rate: 0.75 ml min-1 and temperature: 42 degrees C. Moreover, we looked for the most suitable technique for preparation of plant samples (D. muscipula, Juglans regia, Paulownia tomentosa, Impatience glandulifera, Impatience parviflora, Drosera rotundifolia, Drosera spathulata and Drosera capensis) due to their consequent analysis by HPLC-DAD. It clearly follows from the results obtained that sonication were the most suitable technique for preparation of J. regia plants. We also checked the recoveries of the determined naphthoquinones, which were from 96 to 104%. Finally, we investigated the changes in content of plumbagin in D. muscipula plants according to different pH of cultivation medium. The content increased with increasing pH up to 5 and, then, changed gradually. The lower content of plumbagin at lower pH values was of interest to us. Therefore, we determined the content of this naphthoquinone in the cultivation medium, what has not been studied before. We discovered that the lower tissue content of plumbagin was due to secretion of this naphthoquinone into the cultivation medium. PMID:16765109

Babula, Petr; Mikelova, Radka; Adam, Vojtech; Kizek, Rene; Havel, Ladislav; Sladky, Zdenek

2006-09-14

99

1,4-Naphthoquinones and Others NADPH-Dependent Glutathione Reductase-Catalyzed Redox Cyclers as Antimalarial Agents  

PubMed Central

The homodimeric flavoenzyme glutathione reductase catalyzes NADPH-dependent glutathione disulfide reduction. This reaction is important for keeping the redox homeostasis in human cells and in the human pathogen Plasmodium falciparum. Different types of NADPH-dependent disulfide reductase inhibitors were designed in various chemical series to evaluate the impact of each inhibition mode on the propagation of the parasites. Against malaria parasites in cultures the most potent and specific effects were observed for redox-active agents acting as subversive substrates for both glutathione reductases of the Plasmodium-infected red blood cells. In their oxidized form, these redox-active compounds are reduced by NADPH-dependent flavoenzyme-catalyzed reactions in the cytosol of infected erythrocytes. In their reduced forms, these compounds can reduce molecular oxygen to reactive oxygen species, or reduce oxidants like methemoglobin, the major nutrient of the parasite, to indigestible hemoglobin. Furthermore, studies on a fluorinated suicide-substrate of the human glutathione reductase indicate that the glutathione reductase-catalyzed bioactivation of 3-benzylnaphthoquinones to the corresponding reduced 3-benzoyl metabolites is essential for the observed antimalarial activity. In conclusion, the antimalarial lead naphthoquinones are suggested to perturb the major redox equilibria of the targeted cells. These effects result in development arrest of the parasite and contribute to the removal of the parasitized erythrocytes by macrophages.

Belorgey, Didier; Lanfranchi, Don Antoine; Davioud-Charvet, Elisabeth

2013-01-01

100

Naphthoquinone-Dependent Generation of Superoxide Radicals by Quinone Reductase Isolated from the Plasma Membrane of Soybean[W  

PubMed Central

Using a tetrazolium-based assay, a NAD(P)H oxidoreductase was purified from plasma membranes prepared from soybean (Glycine max) hypocotyls. The enzyme, a tetramer of 85 kD, produces O2·? by a reaction that depended on menadione or several other 1,4-naphthoquinones, in apparent agreement with a classification as a one-electron-transferring flavoenzyme producing semiquinone radicals. However, the enzyme displayed catalytic and molecular properties of obligatory two-electron-transferring quinone reductases of the DT-diaphorase type, including insensitivity to inhibition by diphenyleneiodonium. This apparent discrepancy was clarified by investigating the pH-dependent reactivity of menadionehydroquinone toward O2 and identifying the protein by mass spectrometry and immunological techniques. The enzyme turned out to be a classical NAD(P)H:quinone-acceptor oxidoreductase (EC 1.6.5.2, formerly 1.6.99.2) that reduces menadione to menadionehydroquinone and subsequently undergoes autoxidation at pH ? 6.5. Autoxidation involves the production of the semiquinone as an intermediate, creating the conditions for one-electron reduction of O2. The possible function of this enzyme in the generation of O2·? and H2O2 at the plasma membrane of plants in vivo is discussed.

Schopfer, Peter; Heyno, Eiri; Drepper, Friedel; Krieger-Liszkay, Anja

2008-01-01

101

Synthesis and anticancer activity of some novel 5,6-fused hybrids of juglone based 1,4-naphthoquinones.  

PubMed

Six novel 5,6-fused hybrids such as dihydrobenzofuran-quinone (4a and 4b), benzofuran-quinone (5a and 5b) and chromene-quinone (6a and 6b) of juglone based 1,4-naphthoquinones were synthesized by employing a three step protocol with the cyclisation of o-allyl phenol as the key step. The anticancer activity of the newly synthesized compounds was evaluated in vitro against seven human cancer cell lines including cervix (ME-180 and HeLa), breast (MCF-7, MDA-MB-453 and MDA-MB-231), prostate (PC-3) and colon (HT-29) by using MTT assay. The screening results showed that majority of the synthesized compounds exhibited significant anticancer activity. In particular, compounds 6a and 6b showed potent activities than the standard drug etoposide against prostate and breast cancer cell lines respectively. Flow cytometric analysis revealed that compounds 6a and 6b induced apoptosis and arrested the cell cycle at G2/M phase in PC-3 and MDA-MB-453 cells respectively. PMID:24953027

Mallavadhani, Uppuluri Venkata; Prasad, Chakka Vara; Shrivastava, Shweta; Naidu, V G M

2014-08-18

102

The biosynthetic pathway for aurofusarin in Fusarium graminearum reveals a close link between the naphthoquinones and naphthopyrones.  

PubMed

Fungal polyketide biosynthesis typically involves multiple enzymatic steps and the encoding genes are often found in gene clusters. A gene cluster containing PKS12, the polyketide synthase gene responsible for the synthesis of the pigment aurofusarin, was analysed by gene replacement using Agrobacterium tumefaciens-mediated transformation to determine the biosynthesis pathway of aurofusarin. Replacement of aurR1 with hygB shows that it encodes a positively acting transcription factor that is required for the full expression of PKS12, aurJ, aurF, gip1 and FG02329.1, which belong to the gene cluster. AurR1 and PKS12 deletion mutants are unable to produce aurofusarin and rubrofusarin. Bio- and chemoinformatics combined with chemical analysis of replacement mutants (DeltaaurJ, DeltaaurF, Deltagip1, DeltaaurO and DeltaPKS12) indicate a five-step enzyme catalysed pathway for the biosynthesis of aurofusarin, with rubrofusarin as an intermediate. This links the biosynthesis of naphthopyrones and naphthoquinones together. Replacement of the putative transcription factor aurR2 results in an increased level of rubrofusarin relative to aurofusarin. Gip1, a putative laccase, is proposed to be responsible for the dimerization of two oxidized rubrofusarin molecules resulting in the formation of aurofusarin. PMID:16879655

Frandsen, Rasmus J N; Nielsen, Nikoline J; Maolanon, Nicolai; Sørensen, Jens C; Olsson, Stefan; Nielsen, John; Giese, Henriette

2006-08-01

103

Microsomal oxidation of 2-dimethylamino-3-chloro-1,4-naphthoquinone. The possibility of substrate activation by cytochrome P-450.  

PubMed

2-Dimethylamino-3-chloro-1,4-naphthoquinone (DCNQ) is bound to microsomal cytochrome P-450 as a type I substrate (lambda max = 391 nm, lambda min = 420 nm). The Ks is 40.5 microM. In a rat-liver microsomal system, the N-demethylation of DCNQ produces formaldehyde (rate 225 pmol/min per mg of protein). Induction by phenobarbital increases the rate of formation, while addition of metyrapone and SKF-525A into the system decreases the rate by 52% and 35%, respectively. The microsomal N-demethylation of DCNQ is not inhibited by CO. Under full anaerobiosis, the microsomal oxidation of DCNQ again gives formaldehyde (rate 416 pmol/min per mg of protein). The anaerobic oxidation of DCNQ is inhibited by metyrapone and SKF-525A. The microsomal, chemical and electrochemical reduction of DCNQ to the corresponding semiquinones and hydroquinones have been studied. Non-enzymic DCNQ reduction is insufficient for the formation of formaldehyde. Under anaerobic conditions the microsomal DCNQ oxidation is assumed to occur via the intramolecular oxazole bond which is then hydrolysed, yielding formaldehyde. This may be a new example of substrate activation by cytochrome P-450. PMID:3962336

Rumyantseva, G V; Sushkov, D G; Weiner, L M

1986-02-01

104

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

105

Distribution of naphthoquinones, plumbagin, droserone, and 5-O-methyl droserone in chitin-induced and uninduced Nepenthes khasiana: molecular events in prey capture.  

PubMed

Prey capture and digestion in Nepenthes spp. through their leaf-evolved biological traps involve a sequence of exciting events. Sugar-rich nectar, aroma chemicals, narcotic alkaloid secretions, slippery wax crystals, and other biochemicals take part in attracting, capturing, and digesting preys in Nepenthes pitchers. Here we report the distribution of three potent naphthoquinones in Nepenthes khasiana and their roles in prey capture. Plumbagin was first detected in N. khasiana, and its content (root: 1.33 ± 0.02%, dry wt.) was the highest found in any natural source. Chitin induction enhanced plumbagin levels in N. khasiana (root: 2.17 ± 0.02%, dry wt.). Potted N. khasiana plants with limited growth of roots and aerial parts, showed higher levels of plumbagin accumulation (root: 1.92 ± 0.02%; root, chitin induction: 3.30 ± 0.21%, dry wt.) compared with field plants. Plumbagin, a known toxin, insect ecdysis inhibitor, and antimicrobial, was also found embedded in the waxy layers at the top prey capture region of N. khasiana pitchers. Chitin induction, mimicking prey capture, produced droserone and 5-O-methyl droserone in N. khasiana pitcher fluid. Both these naphthoquinone derivatives provide antimicrobial protection to the pitcher fluid from visiting preys. A two-way barrier was found between plumbagin and its two derivatives. Plumbagin was never detected in the pitcher fluid whereas both its derivatives were only found in the pitcher fluid on chitin induction or prey capture. The three naphthoquinones, plumbagin, droserone, and 5-O-methyl droserone, act as molecular triggers in prey capture and digestion in the carnivorous plant, N. khasiana. PMID:21862483

Raj, Gopan; Kurup, Rajani; Hussain, Abdul Azeez; Baby, Sabulal

2011-11-01

106

Preparation of 2-methyl-1,4-naphthoquinone (vitamin K 3) by catalytic oxidation of 2-methyl-1-naphthol in the presence of iron phthalocyanine supported catalyst  

Microsoft Academic Search

Iron tetrasulfophthalocyanine (FePcS) supported catalyst was prepared by covalent grafting onto amino-modified silica by a novel practical one-pot method using activation of sulfonate groups of FePcS by triphenylphosphine triflate. FePcS–SiO2 in combination with tBuOOH behaved as an efficient catalyst for the oxidation of 2-methyl-1-naphthol to 2-methyl-1,4-naphthoquinone, vitamin K3. To optimise the catalytic system, the influence of different reaction parameters on

Olga V. Zalomaeva; Oxana A. Kholdeeva; Alexander B. Sorokin

2007-01-01

107

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

108

Tabebuia avellanedae naphthoquinones: activity against methicillin-resistant staphylococcal strains, cytotoxic activity and in vivo dermal irritability analysis  

PubMed Central

Background Methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococcus infections are a worldwide concern. Currently, these isolates have also shown resistance to vancomycin, the last therapy used in these cases. It has been observed that quinones and other related compounds exhibit antibacterial activity. This study evaluated the antibacterial activity, toxicity and in vivo dermal irritability of lapachol extracted from Tabebuia avellanedae and derivatives against methicillin-resistant staphylococcal isolates. In addition, its mechanism of action was also analyzed. Methods The compounds ?-lapachone, 3-hydroxy ? N lapachone and ?-lapachone were tested to determine the MIC values against methicillin-resistant S. aureus, S. epidermidis and S. haemolyticus strains, being the two last ones hetero-resistant to vancomycin. Experiments of protein synthesis analysis to investigate the naphthoquinones action were assessed. In vitro toxicity to eukaryotic BSC-40 African Green Monkey Kidney cell cultures and in vivo primary dermal irritability in healthy rabbits were also performed. Results The compounds tested showed antibacterial activity (MICs of 8, 4/8 and 64/128 ?g/mL to ?-lapachone, 3-hydroxy ? N lapachone and ?-lapachone, respectively), but no bactericidal activity was observed (MBC > 512 ?g/mL for all compounds). Although it has been observed toxic effect in eukaryotic cells, the compounds were shown to be atoxic when applied as topic preparations in healthy rabbits. No inhibition of proteins synthesis was observed. Conclusion Our results suggest that quinones could be used in topic preparations against wound infections caused by staphylococci, after major investigation of the pharmacological properties of the compounds. Studies about the use of these compounds on tumoral cells could be carried on, due to their effect in eukaryotic cells metabolism.

Pereira, Eliezer Menezes; Machado, Thelma de Barros; Leal, Ivana Correa Ramos; Jesus, Desyree Murta; Damaso, Clarissa Rosa de Almeida; Pinto, Antonio Ventura; Giambiagi-deMarval, Marcia; Kuster, Ricardo Machado; dos Santos, Katia Regina Netto

2006-01-01

109

Co-induction of methyltransferase Rv0560c by naphthoquinones and fibric acids suggests attenuation of isoprenoid quinone action in Mycobacterium tuberculosis.  

PubMed

The superoxide generator menadione was previously demonstrated as an inducer of growth stage dependent protein patterns in Mycobacterium tuberculosis. The present study refines this observation by characterizing a novel 27-kDa protein that had not been observed in previous studies relying on younger cultures. A very similar response, based on two-dimensional gel electrophoretic analyses, was induced by the closely related naphthoquinone plumbagin. The 27-kDa protein was also induced by the pro-oxidant peroxisome proliferator gemfibrozil and to a lesser extent by the structurally related compounds fenofibrate and clofibrate. N-terminal sequence data of proteolytic fragments from the 27-kDa protein demonstrated its identity with protein Rv0560c, previously demonstrated to be inducible by salicylate, which also possesses peroxisome proliferating properties. Protein Rv0560c bears three conserved motifs characteristic of S-adenosylmethionine-dependent methyltransferases. Further sequence similarities suggest a function in the bio syn thesis of isoprenoid compounds, e.g., tocopherol, ubiquinone, and sterols. Such involvement is supported by the recognized yet unexplained widespread interference of menadione, salicylate, and fibrates with the isoprenoid quinones ubiquinone, menaquinone, and vitamin K. Induction of Rv0560c by fibrates, salicylate, and naphthoquinones is thus suggested to be caused by action on the plasma membrane, reminiscent of cytochrome P450BM-3 induction by fibrates in Bacillus megaterium, which catalyzes the hydroxylation of fatty acids and thus modulates membrane properties. PMID:15644891

Garbe, Thomas R

2004-10-01

110

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.

2013-01-01

111

Validated spectrophotometric method for the determination, spectroscopic characterization and thermal structural analysis of duloxetine with 1,2-naphthoquinone-4-sulphonate  

NASA Astrophysics Data System (ADS)

A novel, selective, sensitive and simple spectrophotometric method was developed and validated for the determination of the antidepressant duloxetine hydrochloride in pharmaceutical preparation. The method was based on the reaction of duloxetine hydrochloride with 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline media to yield orange colored product. The formation of this complex was also confirmed by UV-visible, FTIR, 1H NMR, Mass spectra techniques and thermal analysis. This method was validated for various parameters according to ICH guidelines. Beer's law is obeyed in a range of 5.0-60 ?g/mL at the maximum absorption wavelength of 480 nm. The detection limit is 0.99 ?g/mL and the recovery rate is in a range of 98.10-99.57%. The proposed methods was validated and applied to the determination of duloxetine hydrochloride in pharmaceutical preparation. The results were statistically analyzed and compared to those of a reference UV spectrophotometric method.

Ulu, Sevgi Tatar; Elmali, Fikriye Tuncel

2012-03-01

112

Inhibitory effect of a novel naphthoquinone derivative on proliferation of vascular smooth muscle cells through suppression of platelet-derived growth factor receptor ? tyrosine kinase.  

PubMed

This study was designed to investigate the antiproliferative effect of a novel naphthoquinone derivative, 2-undecylsulfonyl-5,8-dimethoxy-1,4-naphthoquinone (2-undecylsulfonyl-DMNQ), on platelet-derived growth factor (PDGF)-stimulated vascular smooth muscle cells (VSMCs) and examine the possible molecular mechanism of its antiproliferative action. 2-Undecylsulfonyl-DMNQ significantly inhibited PDGF-stimulated cell number and DNA synthesis, and arrested the PDGF-stimulated progression through G0/G1 to S phase of cell cycle supported by the suppression of pRb phosphorylation and cyclin D1/E, CDK2/4 and PCNA expressions. 2-Undecylsulfonyl-DMNQ dose-dependently inhibited the PDGF-stimulated phosphorylation of phospholipase C? (PLC?), protein kinase B (Akt/PKB), signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinase 1/2 (ERK 1/2). In addition, 2-undecylsulfonyl-DMNQ inhibited PDGF-induced PDGF receptor ? (PDGF-R?) dimerization and the phosphorylation of Tyr(579/581), Tyr(716), Tyr(751) and Tyr(1021) in PDGF-R?. However, 2-undecylsulfonyl-DMNQ has no antiproliferative effect on epidermal growth factor (EGF)- or fetal bovine serum (FBS)-stimulated VSMCs. In conclusion, these findings suggest that the antiproliferative effects of 2-undecylsulfonyl-DMNQ on PDGF-stimulated VSMCs are due to the blockade of receptor dimerization and autophosphorylation on specific tyrosine residues of PDGF-R?, which resulted in the subsequent suppression of signaling cascades and a cell cycle arrest. Our observation may explain an important mechanism to block the integration of multiple signals generated by growth factor receptor activation for prevention of VSMC proliferation in cardiovascular diseases. PMID:24695376

Kim, Yohan; Han, Joo-Hui; Yun, Eunju; Jung, Sang-Hyuk; Lee, Jung-Jin; Song, Gyu-Yong; Myung, Chang-Seon

2014-06-15

113

2Hydroxy1,4-naphthoquinone, the natural dye of Henna, is non-genotoxic in the mouse bone marrow micronucleus test and does not produce oxidative DNA damage in Chinese hamster ovary cells  

Microsoft Academic Search

2-Hydroxy-1,4-naphthoquinone (HNQ) has been found positive in a previous chromosome aberration test in Chinese hamster ovary (CHO) cells and in a mouse bone marrow micronucleus test at 72h after oral administration (vehicle: DMSO). However it was negative at 24 and 48h sampling times, and in subsequent micronucleus tests that used 0.5% aqueous methyl cellulose (MC) as vehicle. We performed a

Daniel Marzin; David Kirkland

2004-01-01

114

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  

Microsoft Academic Search

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

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

2008-01-01

115

2Methyl1,4-naphthoquinone, Vitamin K3, Decreases Gap-Junctional Intercellular Communication via Activation of the Epidermal Growth Factor Receptor\\/Extracellular Signal-regulated Kinase Cascade1  

Microsoft Academic Search

Methyl-1,4-naphthoquinone, vitamin K3 (menadione), which is fre- quently used as a model quinone in cell culture and in vivo studies, was tested for its effects on gap-junctional intercellular communication (GJC). Exposure of WB-F344 rat liver epithelial cells to menadione (50 -100 M) led to a 50 -75% decrease in GJIC. Different from the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, menadione did not

Lars-Oliver Klotz; Pauline Patak; Niloofar Ale-Agha; Darius P. Buchczyk; Kotb Abdelmohsen; P. Arne Gerber; Claudia von Montfort; Helmut Sies

116

Effect of l-phenylalanine on PAL activity and production of naphthoquinone pigments in suspension cultures of Arnebia euchroma (Royle) Johnst.  

PubMed

The effects of l-phenylalanine (PHE) on cell growth and production of shikonin and its derivatives, acetylshikonin (ACS) and isobutyrylshikonin (IBS), in suspension cultures of Arnebia euchroma were examined. Supplementing media using PHE have been successfully utilized to enhance shikonin production in cell cultures of other species of Boraginaceae. l-Phenylalanine, the key compound in the phenylpropanoid pathway, is converted by phenylalanine ammonia lyase (PAL) to trans-cinnamic acid, which is the precursor of p-hydroxybenzoic acid (PHB). Coupling of PHB and geranyl pyrophosphate (derived from mevalonate pathway) by p-hydroxybenzoate-m-geranyltransferase leads later to biosynthesis of shikonins. The addition of 0.01 or 0.1 mM PHE to the culture medium stimulated cell proliferation, where the highest observed increase in fresh cell biomass (measured as a ratio of final weight to initial weight) was 12-fold, in contrast to an eightfold increase in control cultures. Whereas, growth media supplemented with 1 mM PHE markedly reduced the rate of cell growth (to only twofold). Precursor feeding had detrimental effects on both ACS and IBS production in all PHE-supplemented media. The highest total content (intracellular + extracellular) of the investigated red pigments (9.5 mg per flask) was detected in the control culture without PHE. ACS was the major component of the naphthoquinone fraction determined in cells and post-culture media. Shikonin itself was found only in the post-culture media from cultures supplemented with 0.01 or 0.1 mM PHE. Increases in PAL activity corresponded well with the accumulation of investigated naphthoquinones in control culture. However, peak PAL activity did not directly correlate with maximum production of shikonin derivatives. Cytotoxicity of extracts, prepared from the cells cultivated in the presence of PHE or in control cultures, was tested on three cancer cell lines: HL-60, HeLa, and MCF-7. The extracts prepared from the untreated control cultures proved to be the most potent against the examined cancer cell lines. The mean inhibitory concentration values were 0.3, 13, and 8 ?g ml(-1) for the HL-60, HeLa, and MCF-7 cells, respectively. PMID:23049233

Syk?owska-Baranek, Katarzyna; Pietrosiuk, Agnieszka; Naliwajski, Marcin R; Kawiak, Anna; Jeziorek, Ma?gorzata; Wyderska, Sylwia; Lojkowska, Ewa; Chinou, Ioanna

2012-10-01

117

Magnetic field effects on the reaction of the photoexcited triplet of 2-methyl-1,4-naphthoquinone in SDS micellar solution containing the 4-(lauroylamino)-TEMPO radical  

NASA Astrophysics Data System (ADS)

A study has ben made of magnetic field effects (MFEs) on the reaction of the photoexcited triplet of 2-methyl-1,4-naphthoquinone (MNQ) in SDS micellar solution containing the 4-lauroylamino-TEMPO radical (L-R·) under magnetic fields below 1.75 T by a nanosecond laser flash photolysis technique. The triplet MNQ mainly underwent the hydrogen abstraction from an SDS molecule to give a radical pair. The lifetime of the radical pair increased with increasing magnetic field from 0 to 0.62 T. The escaped radical yield also increased from 0 to 1.75 T. The qualitative features of these MFEs were similar to those observed for the photoreduction of MNQ in SDS micellar solution without L-R·, and these MFEs can be explained by the relaxation mechanism. However, it was found that L-R· affected the MFEs for this reaction in two ways: first, L-R· reacted with the triplet MNQ through H abstraction and/or electron transfer, and second, the spin relaxation of the radical pair was enhanced through the spin-spin interactions of the individual radical with L-R·.

Chen, Jiafu; Mori, Yukie; Sakaguchi, Yoshio; Hayashi, Hisaharu

118

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

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

2009-01-01

119

2-Amino-3-carboxy-1,4-naphthoquinone affects the end-product profile of bifidobacteria through the mediated oxidation of NAD(P)H.  

PubMed

Glucose metabolism of bifidobacteria in the presence of 2-amino-3-carboxy-1,4-naphthoquinone (ACNQ), a specific growth stimulator for bifidobacteria, and ferricyanide (Fe(CN)(6)(3-)) as an extracellular electron acceptor was examined using resting cells of Bifidobacterium longum and Bifidobacterium breve. NAD(P)H in the cells is oxidized by ACNQ with the aid of diaphorase activity, and reduced ACNQ donates the electron to Fe(CN)(6)(3-). Exogenous oxidation of NADH by the ACNQ/Fe(CN)(6)(3-) system suppresses the endogenous lactate dehydrogenase reaction competitively, which results in the remarkable generation of pyruvate and a decrease in lactate production. In addition, a decrease in acetate generation is also observed in the presence of ACNQ and Fe(CN)(6)(3-). This phenomenon could not be explained in terms of the fructose-6-phosphate phosphoketolase pathway, but suggests rather that glucose is partially metabolized via the hexose monophosphate pathway. This was verified by NADP(+)-induced reduction of Fe(CN)(6)(3-) in cell-free extracts in the presence of ACNQ. Effects of the ACNQ/Fe(CN)(6)(3-) system on anaerobically harvested cells were also examined. Stoichiometric analysis of the metabolites from the pyruvate-formate lyase pathway suggests that exogenous oxidation of NADH is an efficient method to produce ATP in this pathway. PMID:12073135

Yamazaki, S; Kaneko, T; Taketomo, N; Kano, K; Ikeda, T

2002-06-01

120

Gallium(III) selective sensors based on 2-amino-3-(alpha-N-phenylmethyl-2'-amino-1',4'-naphthoquinonyl)-1,4 naphthoquinones in poly (vinyl chloride).  

PubMed

Synthesis and application of 2-amino-3-(alpha-N-phenylmethyl-2'-amino-1',4'-naphthoquinonyl)-1,4 naphthoquinone (S) as a neutral ionophore for the determination of gallium(III) in PVC-based membrane sensors has been described. The sensor based on membrane composition (w/w, mg%); 5.0 (S):30.0 (PVC):5.0 (KTpClPB):60.0 (o-NPOE) is the best and showed a working range of 2.3x10(-7) to 1.0x10(-2) M with detection limit of 1.2x10(-7) M. It can tolerate non-aqueous media up to 15% with a slope of 19.7 mV decade(-1) of activity. The sensor has been used to assess the Ga(III) concentration in different natural samples (peach and tomato leaves, coal-fly-ash and river sediments). It can be used for 2.5 months without any distortion in results, after which, leaching of ionophore was observed from the membrane phase. The proposed sensor has shown a good dynamic response time of 11 s. PMID:20599027

Gupta, Vinod K; Hamdan, A J; Pal, Manoj K

2010-07-19

121

Involvement of sensory nerves and TRPV1 receptors in the rat airway inflammatory response to two environment pollutants: diesel exhaust particles (DEP) and 1,2-naphthoquinone (1,2-NQ)  

Microsoft Academic Search

The environmental chemical 1,2-naphthoquinone (1,2-NQ) is implicated in the exacerbation of airways diseases induced by exposure\\u000a to diesel exhaust particles (DEP), which involves a neurogenic-mediated mechanism. Plasma extravasation in trachea, main bronchus\\u000a and lung was measured as the local 125I-bovine albumin accumulation. RT-PCR quantification of TRPV1 and tachykinin (NK1 and NK2) receptor gene expression were investigated in main bronchus. Intratracheal

Aila Mirtes Teles; Yoshito Kumagai; Susan D. Brain; Simone A. Teixeira; Ana A. Varriano; Maria Alice A. G. Barreto; Wothan Tavares de Lima; Edson Antunes; Marcelo N. Muscará; Soraia K. P. Costa

2010-01-01

122

Catalytic Synthesis of 2Methyl1,4Naphthoquinone (Vitamin K3) Over Silica-Supported Aminomethyl Phosphine-Ru(II), Pd(II), and Co(II) Complexes  

Microsoft Academic Search

Ru(II), Pd(II), and Co(II) complexes of the free ditertiary aminomethylphosphine ligand, N,N-bis(diphenylphosphinomethyl)aminopropyltriethoxysilane [(EtO)3Si(CH2)3 N(CH2PPh2)2] (DIPAPTES), and its SiO2-DIPAPES have been synthesized under a nitrogen atmosphere using Schlenk techniques. All the complexes were used as catalysts for the oxidation of 2-methyl naphthalene (2MN) to give 2-methyl-1,4-naphthoquinone (vitamin K3, menadione, 2MNQ) in the presence of hydrogen peroxide as a clean and cheap

Serhan Uru?; Mustafa Kele?; Osman Serinda?

2010-01-01

123

Synthesis of Silica-Supported Platinum(II) and Nickel(II) Complexes of Bis (Diphenylphosphinomethyl)Amino Ligand: Applications as Catalysts for the Synthesis of 2Methyl1,4Naphthoquinone (Vitamin K 3 )  

Microsoft Academic Search

Pt(II) and Ni(II) complexes of N,N-bis(diphenylphosphinomethyl)aminopropyltriethoxysilane [(CH3CH2O)3Si(CH2)3N(CH2PPh2)2] (DIPAPTES) and silica supported [SiO2–(DIPAPES)] ligands have been synthesized under nitrogen atmosphere using Schlenk method and characterized by using atomic\\u000a absorption, FT-IR, NMR (1H and 31P) and elemental analysis techniques. All the complexes were used as catalysts for the oxidation of 2-methyl naphthalene (2MN)\\u000a to 2-methyl-1,4-naphthoquinone (vitamin K3, menadione, 2MNQ) using hydrogen peroxide

Serhan Uru?; Mustafa Kele?; Osman Serinda?

2010-01-01

124

Ferrocene and (arene)ruthenium(II) complexes of the natural anticancer naphthoquinone plumbagin with enhanced efficacy against resistant cancer cells and a genuine mode of action.  

PubMed

A series of ferrocene and (arene)ruthenium(II) complexes attached to the naturally occurring anticancer naphthoquinones plumbagin and juglone was tested for efficacy against various cancer cell lines and for alterations in the mode of action. The plumbagin ferrocene and (p-cymene)Ru(II) conjugates 1c and 2a overcame the multi-drug drug resistance of KB-V1/Vbl cervix carcinoma cells and showed IC50 (72h) values around 1?M in growth inhibition assays using 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT). They were further investigated for their influence on the cell cycle of KB-V1/Vbl and HCT-116 colon carcinoma cells, on the generation of reactive oxygen species (ROS) by the latter cell line, for their substrate character for the P-glycoprotein drug eflux pump via the calcein-AM efflux assays, and for DNA affinity by the electrophoretic mobility shift assay (EMSA). The derivatives 1c and 2a increased the number of dead cancer cells (sub-G0/G1 fraction) in a dose- and time-dependent manner. ROS levels were significantly increased upon treatment with 1c and 2a. These compounds also showed a greater affinity to linear DNA than plumbagin. While plumbagin did not affect calcein-AM transport by P-glycoprotein the derivatives 1c and 2a exhibited a 50% or 80% inhibition of the P-glycoprotein-mediated calcein-AM efflux relative to the clinically established sensitizer verapamil. PMID:24907976

Spoerlein-Guettler, Cornelia; Mahal, Katharina; Schobert, Rainer; Biersack, Bernhard

2014-09-01

125

Glutathione-mediated reversibility of covalent modification of ubiquitin carboxyl-terminal hydrolase L1 by 1,2-naphthoquinone through Cys152, but not Lys4.  

PubMed

Covalent modification of cellular proteins by electrophiles affects electrophilic signal transduction and the dysfunction of enzymes that is involved in cytotoxicity. We have recently found a unique reaction which restores glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that has been modified by 1,2-naphthoquinone (1,2-NQ) through a glutathione (GSH)-dependent S-transarylation reaction. We report here that ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) undergoes the same reaction. Exposure of human neuroblastoma SH-SY5Y cells to 1,2-NQ after pretreatment with buthionine sulfoximine (BSO) to deplete GSH resulted in an enhancement of covalent modification of UCH-L1 by 1,2-NQ. With recombinant human UCH-L1, we demonstrated that UCH-L1 underwent arylation by 1,2-NQ through Cys152 and Lys4, thereby decreasing its catalytic activity. Addition of GSH to an incubation mixture of 1,2-NQ-UCH-L1 adduct partially restored this decline in enzyme activity which was accompanied by decreased covalent attachment of 1,2-NQ, together with production of 1,2-NQ-GSH adduct. UCH-L1 in which Lys4 was mutated exhibited a lower level of covalent modification and enzyme inhibition, but completely recovered after addition of GSH. Taken together, these results suggest that Cys152 modification in UCH-L1 by 1,2-NQ is reversible via GSH-mediated S-transarylation reaction whereas Lys4 modification by 1,2-NQ is irreversible by GSH. Because UCH-L1 dysfunction has been associated with neurodegeneration, the electrophilic modification of Lys rather than Cys in UCH-L1 may be implicated in such neurodegenerative diseases. PMID:24582816

Toyama, Takashi; Shinkai, Yasuhiro; Yazawa, Aki; Kakehashi, Hidenao; Kaji, Toshiyuki; Kumagai, Yoshito

2014-05-01

126

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

127

Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones  

PubMed Central

Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz) and nifurtimox (Nf)) developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies for CD and investigate the in vitro and in vivo efficacy, toxicity, selectivity, and parasite targets of different classes of natural and synthetic compounds. Some of these results will be briefly presented, focusing primarily on diamidines and related compounds and naphthoquinone derivatives that showed the most promising efficacy against T. cruzi.

de Castro, Solange L.; Batista, Denise G. J.; Batista, Marcos M.; Batista, Wanderson; Daliry, Anissa; de Souza, Elen M.; Menna-Barreto, Rubem F. S.; Oliveira, Gabriel M.; Salomao, Kelly; Silva, Cristiane F.; Silva, Patricia B.; Soeiro, Maria de Nazare C.

2011-01-01

128

Oxygen uptake upon photolysis of 1,4-benzoquinones and 1,4-naphthoquinones in air-saturated aqueous solution in the presence of formate, amines, ascorbic acid, and alcohols.  

PubMed

The effects of oxygen in the photoreduction of 1,4-benzoquinone (BQ), 1,4-naphthoquinone (NQ), and a series of derivatives were studied in aqueous solution in the presence of acetonitrile and formate, aliphatic amines, e.g., EDTA or triethylamine, ascorbic acid, and alcohols, e.g., methanol or 2-propanol. The quinone triplet state is quenched, whereby the semiquinone and donor radicals are formed which react subsequently with oxygen. The overall reaction is oxidation of the donors and conversion of oxygen via the hydroperoxyl/superoxide radical into hydrogen peroxide. The quantum yield (Phi-O2) of this oxygen uptake changes in 2-propanol-water (1:10) from <0.01 for BQ to Phi-O2 = 0.5-0.8 for NQ. Generally Phi-O2 increases with increasing donor concentration. The specific properties of quinone structure, the radical equilibria and reactivity, and the concentration dependences are discussed. PMID:17388578

Görner, Helmut

2007-04-19

129

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.  

PubMed

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. PMID:18343717

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

2008-12-01

130

A UHPLC-MS/MS method for simultaneous determination of six flavonoids, gallic acid and 5,8-dihydroxy-1,4-naphthoquinone in rat plasma and its application to a pharmacokinetic study of Cortex Juglandis Mandshuricae extract.  

PubMed

Cortex Juglandis Mandshuricae is used as a folk remedy for treating cancer, diarrhea and dysentery in traditional Chinese medicine for many years. Six flavonoids (myricitrin, quercitrin, taxifolin, myricetin, quercetin and naringenin), gallic acid and 5,8-dihydroxy-1,4-naphthoquinone are major bioactive components in Cortex Juglandis Mandshuricae extract. In this study, an ultrahigh performance liquid chromatography and tandem mass spectrometry method was developed for simultaneous determination of eight ingredients in rat plasma using chloromycetin as an internal standard. Plasma samples added vitamin C (antioxygen) were acidified with hydrochloric acid and extracted by liquid-liquid extraction with ethyl acetate. Eight ingredients were separated on a Venusil ASB C18 column and detected by multiple reaction monitoring mode using electrospray ionization in the negative ion mode. The method was linear for all analytes over investigated range with all correlation coefficients greater than 0.9900. The validated lower limit of quantification was 20ng/mL for gallic acid, 5ng/mL for myricitrin, 3ng/mL for quercitrin, 10ng/mL for taxifolin, 6ng/mL for myricetin, 3ng/mL for quercetin, 2ng/mL for naringenin and 1?g/mL for 5,8-dihydroxy-1,4-naphthoquinone, respectively. Intra- and inter-day precisions (RSD%) were less than 15% and accuracy (RE%) ranged from -6.9% to 6.9%. The validated method was successfully applied to investigate the pharmacokinetics of the eight analytes after oral administration of Cortex Juglandis Mandshuricae extract to rats. PMID:24704688

Sun, Zhi; Zhao, Longshan; Zuo, Lihua; Qi, Chao; Zhao, Pan; Hou, Xiaohong

2014-05-01

131

Inhibition of electron transfer by 3-alkyl-2-hydroxy-1,4-naphthoquinones in the ubiquinol-cytochrome c oxidoreductases of Rhodopseudomonas sphaeroides and mammalian mitochondria. Interaction with a ubiquinone-binding site and the Rieske iron-sulfur cluster.  

PubMed

3-Alkyl-2-hydroxy-1,4-naphthoquinones (alkyl-HNQ) inhibit Rieske iron-sulfur cluster (Rieske FeS) oxidation and cytochrome b reduction in ubiquinol-cytochrome c oxidoreductase. The effects are the same as those of 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole. Concentrations for 50% inhibition in chromatophores of Rhodopseudomonas sphaeroides (at 0.4 microM reaction center) are 2 microM for undecyl-, 3 microM for octyl-, and 40 microM for pentyl-substituted hydroxynaphthoquinones. The ethyl-substituted and unsubstituted derivatives do not inhibit electron transfer below 2 mM. In chromatophores in which the ubiquinone is partially extracted by isooctane (leaving 4 ubiquinones/reaction center), undecyl-HNQ is effective at 2.5 times lower concentration than in normal chromatophores (30 ubiquinones/reaction center). This observation suggests that the binding of the inhibitor is competitive with ubiquinone. Undecyl-HNQ eliminates the effect that the ubiquinone redox state has on the line shape of the EPR signal of Rieske FeS. This supports the idea that alkyl-HNQ shares a common binding site with ubiquinone which is closely associated with Rieske FeS. The ubiquinone in question has a midpoint oxidation-reduction potential at pH 7 of 90 mV with a -60 mV/pH unit dependency. This value matches that of the ubiquinone pool rather than that of ubiquinone Z, which is functionally recognized as a component "between" cytochrome b and Rieske FeS. When Rieske FeS is oxidized, a 20 times higher concentration of undecyl-HNQ is required for the electron transfer inhibition. This is consistent with the observation that the binding of the inhibitor shifts the midpoint oxidation-reduction potential of Rieske FeS about 60 mV higher, which in turn means that the inhibitor binds about 10 times stronger to the site when Rieske FeS is reduced than when it is oxidized. The observations suggest that 3-alkyl-2-hydroxy-1,4-naphthoquinones inhibit electron transfer by acting as ubiquinone antagonists at a site closely associated with Rieske FeS. PMID:6296106

Matsuura, K; Bowyer, J R; Ohnishi, T; Dutton, P L

1983-02-10

132

Study of the sensitization of tetradecyl benzyl dimethyl ammonium chloride for the color development reaction between lysine and sodium 1,2-naphthoquinone-4-sulfonate and the determination of lysine in pharmaceutical and biological samples  

NASA Astrophysics Data System (ADS)

A rapid, simple and sensitive method for the determination of lysine (Lys) using sodium 1,2-naphthoquinone-4-sulfonate (NQS) and tetradecyl benzyl dimethyl ammonium chloride (Zeph) is presented in this paper. The method is based on the russety product formed from Lys, NQS and Zeph in a buffer solution of pH 9.60, and the stoichiometric ratio of the product is 1:2:2. Beer's law is obeyed in a range of 0.09-18 ?g ml -1 of Lys at the maximum absorption of 474 nm ( ?474 is 8.1 × 10 5 l mol -1 cm -1). The equation of linear regression is A = 0.40427 + 0.06112 C, with a linearly correlation coefficient of 0.9972. The limit of detection is 0.07 ?g ml -1, R.S.D. 0.8%, and average recovery rate in a range of 98.9-100.1%. This paper further optimizes the determination of Lys compared with the previous methods, and the reaction mechanism is studied intensively. The proposed method has been successfully applied to the determination of Lys in pharmaceutical and biological samples. The common components as nutritional additives in pharmaceuticals and other compounds in biological samples nearly do not interfere with the proposed method.

Li, Quanmin; Zhang, Tiantian

2007-06-01

133

Atomic and dynamic insights into the beneficial effect of the 1,4-naphthoquinon-2-yl-L-tryptophan inhibitor on Alzheimer's A?1-42 dimer in terms of aggregation and toxicity.  

PubMed

Aggregation of the amyloid ? protein (A?) peptide with 40 or 42 residues is one key feature in Alzheimer's disease (AD). The 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp) molecule was reported to alter A? self-assembly and reduce toxicity. Though nuclear magnetic resonance experiments and various simulations provided atomic information about the interaction of NQTrp with A? peptides spanning the regions of residues 12-28 and 17-42, none of these studies were conducted on the full-length A?1-42 peptide. To this end, we performed extensive atomistic replica exchange molecular dynamics simulations of A?1-42 dimer with two NQTrp molecules in explicit solvent, by using a force field known to fold diverse proteins correctly. The interactions between NQTrp and A?1-42, which change the A? interface by reducing most of the intermolecular contacts, are found to be very dynamic and multiple, leading to many transient binding sites. The most favorable binding residues are Arg5, Asp7, Tyr10, His13, Lys16, Lys18, Phe19/Phe20, and Leu34/Met35, providing therefore a completely different picture from in vitro and in silico experiments with NQTrp with shorter A? fragments. Importantly, the 10 hot residues that we identified explain the beneficial effect of NQTrp in reducing both the level of A?1-42 aggregation and toxicity. Our results also indicate that there is room to design more efficient drugs targeting A?1-42 dimer against AD. PMID:24246047

Zhang, Tong; Xu, Weixin; Mu, Yuguang; Derreumaux, Philippe

2014-02-19

134

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

135

Modification of Phospholipid Bilayers Induced by Sulfurated Naphthoquinones  

PubMed Central

New thionaphthoquinones and their hydroxyl derivatives, bearing alkyl side chains that match the phospholipids POPC and POPE, were synthesized in order to investigate their interactions with lipids. It was observed that, in general, these additives destabilize the lipid bilayer and induce less organized structures with higher curvature, in particular the induction of an hexagonal phase on aqueous POPC mixtures. Moreover, cubic phases, not normally observed in the pure lipids when fully hydrated, were detected. Coexistence of lamellar phases was interpreted as a consequence of microsegregation of the components in the mixtures. These results are in line with previous observations on the effect of structurally similar (hydro)quinones in phase behavior of these lipids.

Di Vitta, Claudio; Funari, Sergio S.

2013-01-01

136

2,3-Dichloro-5,8-dimeth-oxy-1,4-naphtho-quinone  

PubMed Central

In the crystal structure of the title compound, C12H8Cl2O4, mol­ecules crystallize in planes parallel to (-204) with an inter­planar distance of 3.288?(2)?Å [centroid–centroid distance = 3.819?(2) and slippage = 1.932?(2)?Å]. The structure features C—H?O inter­actions involving meth­oxy and aromatic H atoms and the carbonyl O atoms as well as a C—H?Cl inter­action involving an aromatic H atom. In addition there are short inter­halogen contacts between adjoining mol­ecules [Cl?Cl = 3.3709?(5)?Å].

Ukaegbu, Maraizu; Butcher, Ray J.; Enwerem, N. M.; Bakare, Oladapo; Hosten, Charles

2012-01-01

137

Naphthoquinones from Onosma paniculata induce cell-cycle arrest and apoptosis in melanoma Cells.  

PubMed

Activity-guided fractionation of a petroleum ether-soluble extract of the roots of Onosma paniculata, which has been shown to affect the cell cycle and to induce apoptosis in melanoma cells, led to the isolation of several shikonin derivatives, namely, ?-hydroxyisovalerylshikonin (1), acetylshikonin (2), dimethylacrylshikonin (3), and a mixture of ?-methylbutyrylshikonin and isovalerylshikonin (4+5). All compounds exhibited strong cytotoxicity against eight cancer cell lines and MRC-5 lung fibroblasts, with 3 found to possess the most potent cytotoxicity toward four melanoma cell lines (SBcl2, WM35, WM9, and WM164). Furthermore, 3 and the mixture of 4+5 were found to interfere with cell-cycle progression in these cell lines and led to an increasing number of cells in the subG1 region as well as to caspase-3/7 activation, indicating apoptotic cell death. PMID:22530779

Kretschmer, Nadine; Rinner, Beate; Deutsch, Alexander J A; Lohberger, Birgit; Knausz, Heike; Kunert, Olaf; Blunder, Martina; Boechzelt, Herbert; Schaider, Helmut; Bauer, Rudolf

2012-05-25

138

Molecularly imprinted polymers for the isolation of bioactive naphthoquinones from plant extracts.  

PubMed

Molecularly Imprinted Polymers (MIPs) targeting shikonin, a potent antioxidant and wound healing agent, have been prepared using methacrylic acid (MAA) and 2-diethylaminoethyl methacrylate (DEAEMA) as functional monomers. An investigation of solution association between shikonin and both acidic and basic functional monomers by UV-vis titrations, suggested stronger affinity towards the basic functionality. Strong inhibition of the co-polymerisation reaction of such basic monomers was observed, but was overcome by reduction of the amount of template used during polymer synthesis. Polymer morphology was severely impacted by the template's radical scavenging behaviour as demonstrated by solid state NMR spectroscopy measurements. HPLC evaluation of the final materials in polar conditions revealed limited imprinting effects and selectivity, with the MAA polymers exhibiting marginally better performance. During application of the polymers as MI-SPE sorbents in non-polar solvents it was found that the DEAEMA based polymer was more selective towards shikonin compared to the MAA counterpart, while shikonin recoveries of up to 72% were achieved from hexane solutions of a commercial sample of shikonin, hexane extract of Alkanna tinctoria roots and a commercial pharmaceutical ointment. PMID:24075017

Tsermentseli, Stella K; Manesiotis, Panagiotis; Assimopoulou, Andreana N; Papageorgiou, Vassilios P

2013-11-01

139

In vitro induction of erythrocyte phosphatidylserine translocation by the natural naphthoquinone shikonin.  

PubMed

Shikonin, the most important component of Lithospermum erythrorhizon, has previously been shown to exert antioxidant, anti-inflammatory, antithrombotic, antiviral, antimicrobial and anticancer effects. The anticancer effect has been attributed to the stimulation of suicidal cell death or apoptosis. Similar to the apoptosis of nucleated cells, erythrocytes may experience eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and by phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include the increase of cytosolic Ca2+-activity ([Ca2+]i) and ceramide formation. The present study explored whether Shikonin stimulates eryptosis. To this end, Fluo 3 fluorescence was measured to quantify [Ca2+]i, forward scatter to estimate cell volume, annexin V binding to identify phosphatidylserine-exposing erythrocytes, hemoglobin release to determine hemolysis and antibodies to quantify ceramide abundance. As a result, a 48 h exposure of human erythrocytes to Shikonin (1 µM) significantly increased [Ca2+]i, increased ceramide abundance, decreased forward scatter and increased annexin V binding. The effect of Shikonin (1 µM) on annexin V binding was significantly blunted, but not abolished by the removal of extracellular Ca2+. In conclusion, Shikonin stimulates suicidal erythrocyte death or eryptosis, an effect at least partially due to the stimulation of Ca2+ entry and ceramide formation. PMID:24828755

Lupescu, Adrian; Bissinger, Rosi; Jilani, Kashif; Lang, Florian

2014-05-01

140

Chemistry and hair dyes application of dihydroxy derivatives of anthraquinone and naphthoquinone  

Microsoft Academic Search

Leucoquinizarin reacted with butylamine to give 1-butylamino-4-hydroxyanthraquinone and 1,4-bis(butylamino)anthraquinone. Their structures were elucidated and the reaction mechanism was discussed from the kinetic studies. Quinizarin reacted with butylamine to give 2-butylaminoquinizarin selectively, even in the presence of sodium dithionite. Under a nitrogen atmosphere, quinizarin was butylaminated to give 1-butylamino-4-hydroxyanthraquinone and\\/or 1,4-bis(butylamino)anthraquinone, even in the absence of sodium dithionite. Effects of sodium

Masashi Yoshida

1997-01-01

141

Generation of naphthoquinone radical anions by electrospray ionization: solution, gas-phase, and computational chemistry studies.  

PubMed

Radical anions are present in several chemical processes, and understanding the reactivity of these species may be described by their thermodynamic properties. Over the last years, the formation of radical ions in the gas phase has been an important issue concerning electrospray ionization mass spectrometry studies. In this work, we report on the generation of radical anions of quinonoid compounds (Q) by electrospray ionization mass spectrometry. The balance between radical anion formation and the deprotonated molecule is also analyzed by influence of the experimental parameters (gas-phase acidity, electron affinity, and reduction potential) and solvent system employed. The gas-phase parameters for formation of radical species and deprotonated species were achieved on the basis of computational thermochemistry. The solution effects on the formation of radical anion (Q(•-)) and dianion (Q(2-)) were evaluated on the basis of cyclic voltammetry analysis and the reduction potentials compared with calculated electron affinities. The occurrence of unexpected ions [Q+15](-) was described as being a reaction between the solvent system and the radical anion, Q(•-). The gas-phase chemistry of the electrosprayed radical anions was obtained by collisional-induced dissociation and compared to the relative energy calculations. These results are important for understanding the formation and reactivity of radical anions and to establish their correlation with the reducing properties by electrospray ionization analyses. PMID:21561138

Vessecchi, Ricardo; Naal, Zeki; Lopes, José N C; Galembeck, Sérgio E; Lopes, Norberto P

2011-06-01

142

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

Microsoft Academic Search

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

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

2005-01-01

143

In Vitro Induction of Erythrocyte Phosphatidylserine Translocation by the Natural Naphthoquinone Shikonin  

PubMed Central

Shikonin, the most important component of Lithospermum erythrorhizon, has previously been shown to exert antioxidant, anti-inflammatory, antithrombotic, antiviral, antimicrobial and anticancer effects. The anticancer effect has been attributed to the stimulation of suicidal cell death or apoptosis. Similar to the apoptosis of nucleated cells, erythrocytes may experience eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and by phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include the increase of cytosolic Ca2+-activity ([Ca2+]i) and ceramide formation. The present study explored whether Shikonin stimulates eryptosis. To this end, Fluo 3 fluorescence was measured to quantify [Ca2+]i, forward scatter to estimate cell volume, annexin V binding to identify phosphatidylserine-exposing erythrocytes, hemoglobin release to determine hemolysis and antibodies to quantify ceramide abundance. As a result, a 48 h exposure of human erythrocytes to Shikonin (1 µM) significantly increased [Ca2+]i, increased ceramide abundance, decreased forward scatter and increased annexin V binding. The effect of Shikonin (1 µM) on annexin V binding was significantly blunted, but not abolished by the removal of extracellular Ca2+. In conclusion, Shikonin stimulates suicidal erythrocyte death or eryptosis, an effect at least partially due to the stimulation of Ca2+ entry and ceramide formation.

Lupescu, Adrian; Bissinger, Rosi; Jilani, Kashif; Lang, Florian

2014-01-01

144

The effects on Trypanosoma cruzi of novel synthetic naphthoquinones are mediated by mitochondrial dysfunction  

Microsoft Academic Search

Despite ongoing efforts, the current treatment for Chagas disease is still unsatisfactory, mainly because of the severe side effects and variable efficacy of the available nitroheterocycles. Our group has been assaying natural quinones isolated from Brazilian flora, and their derivatives, as alternative chemotherapeutic agents against Trypanosoma cruzi. From C-allyl lawsone three naphthofuranquinones were synthesized, which were active against trypomastigotes and

Rubem F. S. Menna-Barreto; Renata L. S. Goncalves; Elaine M. Costa; Raphael S. F. Silva; Antonio V. Pinto; Marcus F. Oliveira; Solange L. de Castro

2009-01-01

145

Juglone (5-hydroxy-1,4-naphthoquinone) as a Fish Toxicant  

Microsoft Academic Search

Juglone, a biologically active chemical occurring in various parts of walnut trees, was tested for its toxicity to fish. The 96-hour LC50 values obtained from static bioassays at 12 C range from 27 to 88 parts per billion for rainbow trout, northern pike, goldfish, carp, white suckers, black bullheads, channel catfish, green sunfish and bluegills. The toxicity of juglone to

Leif L. Marking

1970-01-01

146

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

147

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

148

Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species.  

PubMed

Novel ?-lapachone analogs 2-phenyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (NQ1), 2-p-tolyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (NQ3) and 2-methyl-2-phenyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (NQ7), which have trypanocidal activity, were assayed for cytotoxic effects on murine EL-4 T lymphoma cells. The NQs inhibited the proliferation of EL-4 cells at concentrations above 1?M. Nuclear staining of the EL-4 cells revealed chromatin condensation and a nuclear morphology compatible with the induction of apoptosis. Flow cytometry assays with annexin V-FITC and propidium iodide confirmed the cell death by apoptosis. Using electron paramagnetic resonance (EPR), a semiquinone radical was detected in EL-4 cells treated with NQs. In addition, a decrease in the GSH level in parallel with reactive oxygen species (ROS) production was observed. Preincubation with n-acetyl-l-cysteine (NAC) was able to reverse the inhibitory effects of the NQs on cell proliferation, indicating that ROS generation is involved in NQ-induced apoptosis. In addition, the NQs induced a decrease in the mitochondrial membrane potential and increased the proteolytic activation of caspases 9 and 3 and the cleavage of Poly (ADP-Ribose) Polymerase (PARP). In conclusion, these results indicate that redox cycling is induced by the NQs in the EL-4 cell line, with the generation of ROS and other free radicals that could inhibit cellular proliferation as a result of the induction of the intrinsic apoptosis pathway. PMID:23933437

Di Rosso, María Emilia; Barreiro Arcos, María Laura; Elingold, Igal; Sterle, Helena; Baptista Ferreira, Sabrina; Ferreira, Vitor Francisco; Galleano, Mónica; Cremaschi, Graciela; Dubin, Marta

2013-10-01

149

Cytotoxic properties of iron-hydroxynaphthoquinone complexes in rat hepatocytes  

Microsoft Academic Search

The mechanisms of toxicity to isolated rat hepatocytes of Fe(II) and Fe(III) complexes of two structurally related naphthoquinones have been studied. All complexes were found to show a dose-dependent toxicity which precedes cell death. Within the naphthoquinone series the order of toxicity is Fe(II) > parent naphthoquinone > Fe(III). The iron complexes of 5-OH-1,4 naphthoquinone (5-OH-1,4 NQ; Juglone) are more

Avinash Kumbhar; Subhash Padhye; David Ross

1996-01-01

150

Evidence of Polymorphism on the Antitrypanosomal Naphthoquinone (4E)-2-(1H-Pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one  

PubMed Central

The aim of this study was to characterize the solid state properties of (4E)-2-(1H-pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one (BiPNQ), a compound with a significant inhibitory activity against Trypanosoma cruzi, the etiological agent of Chagas disease (American trypanosomiasis). Methods used included Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Fourier Transform Infrared Spectroscopy (FTIR), Powder X-Ray Diffraction (PXRD), Hot Stage, and Confocal Microscopy. Two BiPNQ samples were obtained by crystallization from absolute methanol and 2-propanol-water that exhibited different thermal behaviours, PXRD patterns, and FTIR spectra, indicating the existence of an anhydrous form (BiPNQ-I) and a solvate (BIPNQ-s), which on heating desolvated leading to the anhydrous modification BiPNQ-I. It was determined that FTIR, DSC, and PXRD are useful techniques for the characterization and identification of the crystalline modifications of BiPNQ.

Sperandeo, Norma R.; Faudone, Sonia N.

2013-01-01

151

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

152

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

153

[Influence of fungal elicitor and macroporous resin on shikonin accumulation in hairy roots of Arnebia euchroma (Royle) Johnst].  

PubMed

In order to investigate the effects of fungal elicitor and macroporous adsorption resin on shikonin accumulation in hairy roots of arnebia euchroma (Royle) Johnst, we used spectrophotometry to determine the total naphthoquinone content of the hairy roots, by adding different volume ratio of Aspergillus niger elicitor, Aspergillus oryzae elicitor, and the macroporous resin into the M-9 liquid medium at different culture time. The results show that the total naphthoquinone content was 2.28 times higher than the control when we added mixed elicitors of Aspergillus niger and Aspergillus oryzae at the ratio of 2.5:50 in the 10th day of hairy roots cultivating. The total naphthoquinone content was 3.71 times higher than that of the control, when we added macroporous adsorption resin NKA-9. Aspergillus niger elicitor exhibited synergistic effect with Aspergillus oryzae elicitor to enhance the naphthoquinone. Also, the total naphthoquinone level was 4.17 times higher than that of the control by adding mixed fungal elicitor and macroporous adsorption resin NKA-9 in the bioreactor. Aspergillus oryzae and mixed elicitor could promote the hairy roots proliferation, and macroporous adsorption resin NKA-9 and mixed elicitor increased the total naphthoquinone content. In summary, the measure developed for Arnebia euchroma (Royle) Johnst hairy roots cultivating in bioreactors may potential for large-scale production of naphthoquinone. PMID:23697166

Zhang, Pu; Wang, Fang; Zhu, Chashan

2013-02-01

154

Blight and Disease Control (Selected Articles).  

National Technical Information Service (NTIS)

The control of agricultural pests, diseases, and weeds by foreign and domestic fungicides was tested. The following fungicides were recommended: N-trichloromethylthiotetrahydrophthalamide, 2, 3-dichloro-naphthoquinone-1, 4-, mercurohexane (1% ethylmercuro...

P. Korolev A. Nikoforov A. Leskin

1967-01-01

155

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

156

The Chemistry of Plant and Animal Dyes.  

ERIC Educational Resources Information Center

Provides a brief history of natural dyes. Chemical formulas are provided for flavonoids, luteolin, genistein, brazilin, tannins, terpenes, naphthoquinone, anthraquinone, and dyes with an alkaloid structure. Also discusses chemical background of different dye processes. (CS)

Sequin-Frey, Margareta

1981-01-01

157

Synthesis and cytogenetic effects of aminoquinone derivatives with a di- and a tripeptide.  

PubMed

Quinones are of significant interest due to their important role in specific cellular functions. Quinoproteins are a big class of oxyreductive agents occurring in bacteria and other organisms. In this investigation derivatives of 2-amino-1,4-benzoquinone, 2-amino-1,4-naphthoquinone and 2-amino-5,8-dihydroxy-1,4-naphthoquinone with a di- and a tripeptide were prepared for first time. The effect of the synthesized compounds on sister chomatid exchange (SCE) rates and human lymphocyte proliferation kinetics on a molar basis was studied. Among these coupled products the most effective in inducing SCEs and depressing proliferation rate indices is the coupling product of 2-amino-1,4-naphthoquinone with the tripeptide GHK (10). Next in order of magnitude in inducing cytogenetic effects is 2-amino-1,4-naphthoquinone (2) and its coupling products with glycine and serine (4 and 5), while the rest displayed marginal activity. PMID:11984082

Pachatouridis, C; Iakovidou, Z; Myoglou, E; Mourelatos, D; Pantazaki, A A; Papageorgiou, V P; Kotsis, A; Liakopoulou-Kyriakides, M

2002-04-01

158

Chemical composition fluctuations in roots of Plumbago scandens L. in relation to floral development.  

PubMed

Plumbago scandens L. is a Brazilian tropical/subtropical species that occurs along the coast. Chemically it is mainly represented by naphthoquinones, flavonoids, terpenoids and steroids. The aim of the present work is to study quantitative changes in the root metabolic production of Plumbago scandens during different physiologic developmental stages relative to floration. The results indicated the presence of four substances in the extracts: plumbagin, epi-isoshinanolone, palmitic acid and sitosterol, independent on developmental stage. The naphthoquinone plumbagin has always showed to be the major component of all extracts. Naphthoquinones exhibited their highest content during floration, while the content of the two others components decreased during this stage, revealing an inverse profile. The chemical composition changed depending on the plant requirements. PMID:22146952

Paiva, Selma R; Lima, Lucilene A; Figueiredo, Maria Raquel; Kaplan, Maria Auxiliadora C

2011-12-01

159

Evaluation of plumbagin and its derivative as potential modulators of redox thiol metabolism of Leishmania parasite.  

PubMed

Trypanothione and trypanothione reductase (TryR)-based redox metabolism found in Leishmania and other trypanosomatids exemplify the unique features of this group of organisms. Its absence in mammalian hosts, together with the sensitivity of trypanosomes against oxidative stress, makes this enzyme a unique target for exploitation for potential antileishmanial chemotherapeutics. Plumbagin, a plant-derived naphthoquinone, is reported to possess antileishmanial properties by inhibiting TryR. We here report the kinetics of the inhibitory mechanism of plumbagin and its derivative, 2-methoxy 1, 4-naphthoquinone. Interestingly, apart from acting as inhibitor, these compounds also act as subversive substrates and subvert the physiological function of enzyme by converting it from an antioxidant to a prooxidant. Both naphthoquinones show a significant effect on redox homeostasis and results in increased reactive oxygen species, resulting in morphological changes and parasite death. PMID:21717278

Sharma, Neha; Shukla, Anil Kumar; Das, Mousumi; Dubey, Vikash Kumar

2012-01-01

160

The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells  

Microsoft Academic Search

Naphthazarin (DHNQ, 5,8-dihydroxy-l,4-naphthoquinone) is a naturally available 1,4-naphthoquinone derivatives. In this study,\\u000a we focused on elucidating the cytotoxic mechanism of naphthazarin in A549 non-small cell lung carcinoma cells. Naphthazarin\\u000a reduced the A549 cell viability considerably with an IC50 of 16.4 ± 1.6 ?M. Naphthazarin induced cell death in a dose- and time-dependent manner by activating apoptosis and autophagy\\u000a pathways. Specifically, we found naphthazarin

Bipul R. Acharya; Surela Bhattacharyya; Diptiman Choudhury; Gopal Chakrabarti

2011-01-01

161

Ab initio HF-SCF study of naphthazarin: Geometries, isomerism, hydrogen bonding, and vibrational spectrum  

Microsoft Academic Search

The structural properties and intramolecular hydrogen bonding of a series of structures of naphthazarin molecule were investigated by ab initio HF-SCF methods. The geometries of theC2v,C2h,D2h, andCs symmetry structures were optimized using split-valence basis sets. MP2\\/6-31G*\\/\\/ HF\\/6-31G single-point energy calculations indicate that theC2v isomer (5,8-dihydroxy-1,4-naphthoquinone) is the lowest energy structure of the molecule and that theC2h symmetry one (4,8-dihydroxy-1,5-naphthoquinone), lying

Fabio Ramondo; Luigi Bencivenni

1994-01-01

162

2-Chloro-3-[(2-oxo-2H-chromen-6-yl)amino]-naphthalene-1,4-dione  

PubMed Central

In the title compound, C19H10ClNO4, the dihedral angle between the naphtho­quinone and coumarin rings is 48.99?(6)°. In the crystal, mol­ecules are linked by strong N—H?O hydrogen bonds into chains with graph-set motif C(6) along [101]. The packing also features ?–? stacking inter­actions between naphtho­quinone and coumarin rings [centroid-to-centroid distances = 3.7679?(12) and 3.6180?(13)?Å].

Sousa, Mikaelly O. B.; Silveira, Gleiciani Q.; Gomez, Javier A. G.

2013-01-01

163

Calculation of the absorption wavelength of dyes using time-dependent density-functional theory (TD-DFT)  

Microsoft Academic Search

The absorption wavelengths and oscillator strengths of a series of organic dyes important for the dye industry (indigo, azobenzene, phenylamine, hydrazone, anthraquinone, naphthoquinone and cationic dyes) were calculated using time-dependent density-functional theory. The results were compared with experimental data. TD-DFT correctly reproduced the visible absorption of the dyes.

Dominique Guillaumont; Shinichiro Nakamura

2000-01-01

164

An efficient synthesis of novel fused cycloheptatrienes through Mn(II)-mediated formal intermolecular [2 + 2 + 2 + 1] cycloaddition.  

PubMed

A new method for manganous acetate tetrahydrate mediated formal intermolecular [2 + 2 + 2 + 1] cycloaddition was developed for the synthesis of fused cycloheptatriene derivatives from N-(acylmethyl)pyridinium iodides and naphthoquinone. This method provides an innovative route for the efficient and convenient construction of fused seven-membered carbocycles from simple starting materials. PMID:24564369

Shu, Wen-Ming; Ma, Jun-Rui; Yang, Yan; Wu, An-Xin

2014-03-01

165

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

166

40 CFR Appendix I to Part 192 - Listed Constituents  

Code of Federal Regulations, 2010 CFR

...8b-hexahydro-8a-methoxy-5-methy-, [1aS-(1aα,8β,8aα,8bα)]-) MNNG (Guanidine, N-methyl-Nâ²-nitro-N-nitroso-) Mustard gas (Ethane, 1,1â²-thiobis[2-chloro-) Naphthalene 1,4-Naphthoquinone (1,4-Naphthalenedione)...

2010-07-01

167

The inhibitory activity of natural products on plant p-hydroxyphenylpyruvate dioxygenase  

Microsoft Academic Search

The inhibitory activity of 34 natural products of various structural classes on hydroxyphenylpyruvate dioxygenase (HPPD), the target site for triketone herbicides, and the mode of interaction of selected natural products were investigated. Recombinant HPPD from arabidopsis is sensitive to several classes of natural compounds including, in decreasing order of sensitivity, triketones, benzoquinones, naphthoquinones and anthraquinones. The triketone natural products acted

Giovanni Meazza; Brian E Scheffler; Mario R Tellez; Agnes M Rimando; Joanne G Romagni; Stephen O Duke; Dhammika Nanayakkara; Ikhlas A Khan; Ehab A Abourashed; Franck E Dayan

2002-01-01

168

Rapid assessment of the latent hazard posed by dissolved mercaptans within aqueous effluent  

Microsoft Academic Search

The presence of mercaptans (RSH) can usually be detected by their inherent noxious odour but there is a need to quantify the concentration within effluent and hence allow an assessment of the latent hazard to be made prior to disposal. The versatility of using naphthoquinone as a rapid derivatising agent through which to trap such species has been evaluated. The

Maria Marti Villalba; Verity J. Litchfield; Robert B. Smith; Anthony M. Franklin; Nathan S. Lawrence; James Davis

2008-01-01

169

Theoretical investigation of the rubicordifolin cascade.  

PubMed

The results of a theoretical investigation on the complex cascade reaction leading to the natural product rubicordifolin are reported. These computations analyze the discrete transformations that are required during the conversion of the vinyl naphthoquinone starting material into the natural product, including two pseudopericyclic cyclizations as well as a diastereoselective, hetero-Diels-Alder reaction. PMID:20973524

Lumb, Jean-Philip; Krinsky, Jamin L; Trauner, Dirk

2010-11-19

170

Biosynthesis of menaquinone (vitamin K 2) and ubiquinone (coenzyme Q): A perspective on enzymatic mechanisms  

Microsoft Academic Search

The benzoquinone ubiquinone (coenzyme Q) and the naphthoquinones menaquinone (vitamin K2) and demethylmenaquinone are derived from the shikimate pathway, which has been described as a “metabolic tree with many branches.” Menaquinone (MK) is considered a vitamin, but coenzyme (Q) is not; MK is an essential nutrient (it cannot be synthesized by mammals), whereas Q is not considered an essential nutrient

R Meganathan

2001-01-01

171

Lipoquinones of some bacteria and mycoplasmas, with considerations on their functional significance  

Microsoft Academic Search

In a comparative study the lipoquinones of some chemoorganotrophic, facultatively aerobic bacteria, and representative Acholeplasma, Mycoplasma, Spiroplasma, and Thermoplasma strains were investigated. The quinones were partly purified by preparative thin layer chromatography of lipid extracts, and characterized by their difference spectra (reduced minus oxidized) and Rf values. Respiring bacteria expectedly contained benzoquinones and\\/or naphthoquinones in micromolar concentrations whereas some aerotolerant,

R. Holländer; Gerda Wolf; W. Mannheim

1977-01-01

172

Hydrogen peroxide formation in a surrogate lung fluid by transition metals and quinones present in particulate matter.  

PubMed

Inhaled ambient particulate matter (PM) causes adverse health effects, possibly by generating reactive oxygen species (ROS), including hydrogen peroxide (HOOH), in the lung lining fluid. There are conflicting reports in the literature as to which chemical components of PM can chemically generate HOOH in lung fluid mimics. It is also unclear which redox-active species are most important for HOOH formation at concentrations relevant to ambient PM. To address this, we use a cell-free, surrogate lung fluid (SLF) to quantify the initial rate of HOOH formation from 10 transition metals and 4 quinones commonly identified in PM. Copper, 1,2-naphthoquinone, 1,4-naphthoquinone, and phenanthrenequinone all form HOOH in a SLF, but only copper and 1,2-naphthoquinone are likely important at ambient concentrations. Iron suppresses HOOH formation in laboratory solutions, but has a smaller effect in ambient PM extracts, possibly because organic ligands in the particles reduce the reactivity of iron. Overall, copper produces the majority of HOOH chemically generated from typical ambient PM while 1,2-naphthoquinone generally makes a small contribution. However, measured rates of HOOH formation in ambient particle extracts are lower than rates calculated from soluble copper by an average (±1?) of 44 ± 22%; this underestimate is likely due to either HOOH destruction by Fe or a reduction in Cu reactivity due to organic ligands from the PM. PMID:24857372

Charrier, Jessica G; McFall, Alexander S; Richards-Henderson, Nicole K; Anastasio, Cort

2014-06-17

173

Synthetic lapachol derivatives relax guinea-pig ileum by blockade of the voltage-gated calcium channels.  

PubMed

The present study was designed to further evaluate a possible spasmolytic activity of synthetic lapachol derivatives, norlapachol, alpha-norlapachone, beta-norlapachone and hydro-hydroxy-norlapachol (HH-norlapachol), on guinea-pig ileum. In guinea-pig ileum, except for norlapachol, all naphthoquinones inhibited the phasic contractions induced by carbachol or histamine. Even when the ileum was pre-contracted with KCl, carbachol or histamine, all naphthoquinones induced relaxation, suggesting that these naphthoquinones could be acting on the voltage-gated calcium channels (Ca(V)). As the tonic component this contraction is maintained mainly by the opening of the Ca(V), we hypothesized that these naphthoquinones might be acting on these channels. This hypothesis was confirmed by the observation that norlapachol (pD'2 = 4.99), alpha-norlapachone (pD'2 = 4.49), beta-norlapachone (pD'2 = 6.33), and HH-norlapachol (pD'2 = 4.53) antagonized the contractions induced by CaCl2 in depolarizing medium nominally without Ca2+. As beta-norlapachone was the most potent we decided to continue the study of its action mechanism. The fact that this naphthoquinone has inhibited the tonic contractions induced by S-(-)-Bay K8644 [EC50 = (1.6 +/- 0.30) x 10(-5) M] suggests that the Ca2+ channel involved belongs to the type L (Ca(V)1.2). In addition, in the functional level, the spasmolytic effect of beta-norlapachone does not involve participation of free radicals, since its curve of relaxation was unchanged in the presence of glutathione, an antioxidant agent. PMID:21138067

Cavalcante, Fabiana de A; Monteiro, Fabio de S; Martins, Italo Rossi R; Barbosa, Ticiano P; Camara, Celso de A; Pinto, Angelo C; Vargas, Maria D; da Silva, Bagnólia A

2010-01-01

174

Antibacterial activity of Tabebuia impetiginosa Martius ex DC (Taheebo) against Helicobacter pylori.  

PubMed

The growth-inhibiting activity of Tabebuia impetiginosa Martius ex DC dried inner bark-derived constituents against Helicobacter pylori ATCC 43504 was examined using paper disc diffusion and minimum inhibitory concentration (MIC) bioassays. The activity of the isolated compounds was compared to that of the commercially available anti-Helicobacter pylori agents, amoxicillin, metronidazole, and tetracycline. The biologically active components of Tabebuia impetiginosa dried inner bark (taheebo) were characterized by spectroscopic analysis as 2-(hydroxymethyl)anthraquinone, anthraquinone-2-carboxylic acid, and 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol). With the paper disc diffusion assay 2-(hydroxymethyl)anthraquinone exhibited strong activity against Helicobacter pylori ATCC 43504 at 0.01 mg/disc. Anthraquinone-2-carboxylic acid, lapachol and metronidazole were less effective, exhibiting moderate anti-Helicobacter pylori activity at 0.1 mg/disc. Amoxicillin and tetracycline were the most potent compounds tested, displaying very strong activity at 0.005 mg/disc. 2-(Hydroxymethyl)anthraquinone exhibited moderate activity at this dose. Tetracycline still had strong activity at 0.001 mg/disc while amoxicillin had little activity at this dose. In the MIC bioassay, 2-(hydroxymethyl)anthraquinone (2 microg/mL), anthraquinone-2-carboxylic acid (8 microg/mL), and lapachol (4 microg/mL) were more active than metronidazole (32 microg/mL) but less effective than amoxicillin (0.063 microg/mL) and tetracycline (0.5 microg/mL). The anti-Helicobacter pylori activity of seven 1,4-naphthoquinone derivatives (structurally related to lapachol), 1,4-naphthoquinone, 5,8-dihydroxy-1,4-naphthoquinone (naphthazarin), 2-methyl-1,4-naphthoquinone (menadione), 2-hydroxy-1,4-naphthoquinone (lawsone), 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin), 5-hydroxy-1,4-naphthoquinone (juglone), and 2,3-dichloro-1,4-naphthoquinone (dichlone) was also evaluated using the paper disc assay. Menadione and plumbagin were the most potent compounds tested with the later still exhibiting very strong activity at 0.001 mg/disc. Menadione, juglone and tetracycline had strong activity at this low dose while the latter two compounds and amoxicillin had very strong activity at 0.005 mg/disc. Lawsone was unusual in that it had very strong activity at 0.1 and 0.05 mg/disc but weak activity at doses of 0.01 mg/disc and lower. Naphthazalin, lapachol and dichlone had similar activities while metronidazole had the lowest activity of all compounds tested. These results may be an indication of at least one of the pharmacological actions of taheebo. The Tabebuia impetiginosa dried inner bark-derived materials, particularly 2-(hydroxymethyl)anthraquinone, merit further study as potential Helicobacter pylori eradicating agents or lead compounds. PMID:16359837

Park, Byeoung-Soo; Lee, Hyun-Kyung; Lee, Sung-Eun; Piao, Xiang-Lan; Takeoka, Gary R; Wong, Rosalind Y; Ahn, Young-Joon; Kim, Jeong-Han

2006-04-21

175

[Studies on flash extraction methods of Arnebia euchroma].  

PubMed

The extraction of functional components from radix of Arnebia euchroma was optimized using orthogonal design based on the extraction yields of shikonin, and hydroxyl-naphthoquinone pigments. The data processing was carried out with the multiple guidelines grading method for optimizing the extraction condition. Compared with the traditional method (refluxing and ultrasonic extraction), the flash extraction method was more efficient The optimal conditions were as follows: 95% ethanol extract 3 times with 90 s for each. Under these conditions, the extraction yields of shikonin, and hydroxyl-naphthoquinone pigments were 93.16%, 93.89%, respectively, and the dry extract rate was 5.16%. In conclusion, the result showed that the flash extraction technology was appropriate, stable and feasible. PMID:24199559

Meng, Qing-Ju; Yi, Hong; Yang, Hua; Zhu, Li-Wei; Feng, Jing; Liu, Xiao-Qian

2013-07-01

176

Monoarylhydrazones of alpha-lapachone: synthesis, chemical properties and antineoplastic activity.  

PubMed

The biological activities of the naphthoquinones lapachol, extracted from trees of the genus Tabebuia and its cyclization products alpha and beta-lapachone, have been intensively studied. Giving continuity to the research about new derivatives obtained from the reaction of these naphthoquinones with amino-containing reagents, a series of arylhydrazones of alpha-lapachone was synthesized and their antineoplastic activity was evaluated. This new structure is based on the great electrophilicity of 1,4-quinoidal carbonyl groups towards reagents containing nitrogen as nucleophilic centers, such as arylhydrazines. The products were assayed by the National Cancer Institute (NCI, USA) and their binding to DNA, redox properties and QSAR studies were also determined. PMID:14609278

Renou, S G; Asís, S E; Abasolo, M I; Bekerman, D G; Bruno, A M

2003-10-01

177

WS5995 B, an antifungal agent inducing differential gene expression in the conifer pathogen Heterobasidion annosum but not in Heterobasidion abietinum  

Microsoft Academic Search

The mycorrhization helper bacterium Streptomyces sp. AcH 505 inhibits Norway spruce root infection and colonisation by the root and butt rot fungus Heterobasidion annosum 005 but not by the congeneric strain Heterobasidion abietinum 331 because of higher sensitivity of H. annosum 005 towards the AcH 505-derived naphthoquinone antibiotic WS-5995 B. Differences in antibiotic sensitivity between two isolates\\u000a belonging to two

Nina A. Lehr; Aleksandra Adomas; Frederick O. Asiegbu; Rüdiger Hampp; Mika T. Tarkka

2009-01-01

178

Continuous flow, highly enantioselective Michael additions catalyzed by a PS-supported squaramide.  

PubMed

A polystyrene (PS) supported bifunctional squaramide organocatalyst promotes fast Michael addition of 2-hydroxy-1,4-naphthoquinone to nitroalkenes with very high enantioselectivities at low catalyst loadings. The polystyrene supported catalyst can be recycled up to 10 times without any decrease in enantioselectivity (average 96% ee) and adapted to continuous flow operation (24 h). A single flow experiment involving six different nitroalkenes in a sequential manner highlights the applicability of this methodology for rapid access to chemical diversity. PMID:23837657

Kasaplar, Pinar; Rodríguez-Escrich, Carles; Pericàs, Miquel A

2013-07-19

179

Monitoring of herbicides in river water by gas chromatography-mass spectrometry and solid-phase extraction  

Microsoft Academic Search

A gas chromatography-mass spectrometric method was developed to determine concentrations of herbicides in both the dissolved phases and the suspended phase of river water. The target herbicides were 2-amino-3-chloro-1,4-naphthoquinone, alachlor, benfluralin, bifenox, bromobutide, the debromo form of bromobutide, butachlor, butamifos, chlomethoxyfen, chlornitrofen, chlorpropham, dimepiperate, dimethametryn, dithiopyr, esprocarb, MCPA-ethyl, MCPA-thioethyl, mefenacet, molinate, naproanilide, oxadiazon, pendimethalin, piperophos, pretilachlor, prometryn, simetryn, thiobencard and

Akiko Tanabe; Hideko Mitobe; Kuniaki Kawata; Masaaki Sakai

1996-01-01

180

Efficient and Green Approaches for the Synthesis of 4H-Benzo[g]chromenes in Water, Under Neat Conditions, and Using Task-Specific Ionic Liquid  

Microsoft Academic Search

Facile and convenient procedures have been described for the synthesis of 4H-benzo[g]chromenes by one-pot condensation of aromatic aldehydes, malononitrile\\/ethyl cyanoacetate, and 2-hydroxy-1,4-naphthoquinone. The reaction has been accomplished using catalytic cetyltrimethylammonium bromide (CTAB) in water under reflux or under neat conditions at 110 °C. A task-specific ionic liquid, 1-butyl-3-methyl imidazolium hydroxide ([bmim]OH), has also been found to be an effective catalyst for

Jitender M. Khurana; Devanshi Magoo; Ankita Chaudhary

2012-01-01

181

HPLC with electrochemical detection for determining the distribution of free fatty acids in skin surface lipids from the human face and scalp  

Microsoft Academic Search

Free fatty acids (FFAs) in human skin surface lipids were determined by high-performance liquid chromatography with electrochemical detection. The amperometric detection of FFAs was based on electrochemical reduction of quinone, 2-methyl-1,4-naphthoquinone (vitamin K3, VK3) in unbuffered solution. The peak heights for lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, and arachidonic acids at a detection potential of -415 mV vs

Akira Kotani; Fumiyo Kusu

2002-01-01

182

Benzophenanthridines. IV. Synthesis of the benzo(c)phenanthridine ring from ethyl 6-(3,4-dimethoxyphenylacetyl)-3,4-dimethoxyphenylacetate. 11,12-Diacetoxy-6-methylfagaronine methyl ester perchlorate  

SciTech Connect

The perchlorate of 11,12-diacetoxy-6-methylfaragonine methyl ester was synthesized from ethyl 6-(3,4-dimethoxyphenylacetyl)-3,4-dimethoxyphenylacetate through the formation of the corresponding 2-hydroxy-1,4- and then the 4-isopropyloxy-1,2-naphthaquinones, regioselective amination (leading to the formation of 4-methylamino-3-(3,4-dimethoxyphenyl)-6,7-dimethoxy-1,2-naphthoquinone), and successive reductive acetylation and Bischler-Napiralski cyclization.

Khokhlov, V.A.; Sladkov, V.I.; Kuleshova, L.N.; Suvorov, N.N.

1986-05-20

183

Polyethylene Glycol (PEG 300) and Water–Ethanol as Benign Solvent Systems for the Synthesis of a Novel Series of 2-Hydroxynaphthalen-1(4H)-Ones  

Microsoft Academic Search

An improved, clean, simple, and efficient method for the synthesis of new series of 2-hydroxy-4-methylenenaphthalen-1(4H)-one is described. This new process involves a domino Michael addition of various methylene acid compounds with the sodium salt of 1,2-naphthoquinone-4-sulfonate either in basic (tBuOK) polyethylene glycol (PEG300) at room temperature or in a basic (NaOH) water–ethanol medium at 40 °C by a crushing in a

D. Villemin; M. Benabdallah; N. Choukchou-Braham; B. Mostefa-Kara

2010-01-01

184

Electrochemical analysis of natural solid organic dyes and pigments  

Microsoft Academic Search

Square-wave voltammetry of solid naphthoquinone, anthraquinone, and flavone dyes, carmine, cochineal red, indigo, and Prussian blue, was compared to microanalysis (sample consumption <1 mg) of traditional painting pigments and dyes without their preliminary dissolution. Electrochemical analysis was also performed after the samples' hydrolysis simultaneously with thin-layer chromatography. Anthraquinone-based pigments and Prussian blue are reversibly reduced, cochineal red and lac dyes are

T. Grygar; Š. Ku?ková; D. Hradil; J. Hradilová

2003-01-01

185

Theoretical study on the photochemical properties of naphthazarin and halogen substitution  

Microsoft Academic Search

As a central core of quinone antitumor agents, naphthazarin (5,8-dihydroxy-1,4-naphthoquinone (NA)) has gained much attention in recent years owing to its photosensitive properties. However, there is little theoretical study on the photo-physicochemical behaviors of the compound, which stimulated our interest to perform the study by means of time-dependent density functional theory (TD-DFT) calculations. In this paper, the phototoxic reactions of

DeZhan Chen; ZhaoLing Hao; Xue Zhao; Zhen Wang

2007-01-01

186

Modeling Binding Kinetics at the Q A Site in Bacterial Reaction Centers †  

Microsoft Academic Search

Bacterial reaction centers (RCs) catalyze a series of electron-transfer reactions reducing a neutral quinone to a bound, anionic semiquinone. The dissociation constants and association rates of 13 tailless neutral and anionic benzo- and naphthoquinones for the QA site were measured and compared. The Kd values for these quinones range from 0.08 to 90 µM. For the eight neutral quinones, including

Jennifer Madeo; M. R. Gunner

2005-01-01

187

Anodic oxidation of 2-naphthol at boron-doped diamond electrodes  

Microsoft Academic Search

The anodic oxidation of 2-naphthol in acid media was investigated at a synthetic boron-doped diamond thin film electrode (BDD) using cyclic voltammetry and bulk electrolysis. The results have shown that in the potential region, where the supporting electrolyte is stable, reactions involving simple electron transfer, such as oxidation of 2-naphthol to naphthoxy radical and 1,4-naphthoquinone occur. Polymeric materials, which lead

M. Panizza; P. A. Michaud; G. Cerisola; Ch. Comninellis

2001-01-01

188

Interaction between Chlorophyll a and Vitamin K1 in Monomolecular Films  

Microsoft Academic Search

As part of a continuing study of monolayers containing molecules involved in photosynthesis, we have examined mixed films containing chlorophyll a and vitamin K1 (2-methyl-3-phytyl-1,4-naphthoquinone). This quinone quenches the fluorescence of chlorophyll, both in monolayers highly diluted with oleyl alcohol and in those composed solely of pigment and vitamin K1. Mixed chlorophyll—vitamin K1 monolayers show deviations from ideal behavior, but

G. L. Gaines; A. G. Tweet; W. D. Bellamy

1965-01-01

189

Menadione effect on l -cysteine desulfuration in U373 cells  

Microsoft Academic Search

The non-cytotoxic concentration (20 µM) of menadione (2-methyl-1,4-naphthoquinone), after 1 h of incubation, leads to loss of the activity of rhodanese by 33%, 3-mercaptopyruvate sulfurtrans- ferase by 20%, as well as the level of sulfane sulfur by about 23% and glutathione by 12%, in the culture of U373 cells, in comparison with the control culture. Reactive oxygen species generated by

Maria Wróbel; Halina Jurkowska

190

Bilayer resist system utilizing alkali-developable organosilicon positive photoresist  

Microsoft Academic Search

A bi-layer resist system utilizing an alkali-developable organosilicon positive photoresist (OSPR) has been developed. The composite prepared from an alkali-soluble organosilicon polymer, poly(p- hydroxybenzylsilsesquioxane) and naphthoquinone diazide becomes a alkali-developable positive photoresist which is sensitive to UV (i line - g line) region, and exhibited high oxygen reactive ion etching (O2 RIE) resistance. The sensitivity and the resolution of OSPR

Kazuo Nate; Akiko Mizushima; Hisashi Sugiyama

1991-01-01

191

Interaction of quinones with three pyrimidine bases: A laser flash photolysis study  

Microsoft Academic Search

The interaction between three different pyrimidine bases, uracil (U), cytosine (C) and thymine (T) and two quinones, 2-methyl-1,4-naphthoquinone or menadione (MQ) and 9,10-anthraquinone (AQ) have been studied using laser flash photolysis technique in organic homogeneous medium. The three pyrimidines have revealed a difference in their extent of reactivity towards the quinones, which has been attributed to their structural difference. Our

Adity Bose; Samita Basu

2009-01-01

192

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

Microsoft Academic Search

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

Samita Basu; Adity Bose; Debarati Dey

2008-01-01

193

03219A, a new ?(8,9)-pregnene isolated from Streptomyces sp. SCSIO 03219 obtained from a South China Sea sediment.  

PubMed

03219A (1), a new pregnene steroid possessing a rare ?(8,9)-double bond in the skeleton, together with the known naphthoquinone antibiotic (+)-cryptosporin (2) have been isolated from the fermentation broth of Streptomyces sp. SCSIO 03219, which was isolated from a marine sediment collected in the South China Sea. The structure of 03219A was elucidated using a combination of NMR, MS and X-ray crystallographic methods. PMID:23549354

Zhang, Yun; Zhou, Xiao; Huang, Hongbo; Tian, Xinpeng; Song, Yongxiang; Zhang, Si; Ju, Jianhua

2013-06-01

194

Scanning electrochemical microscopy of menadione-glutathione conjugate export from yeast cells  

Microsoft Academic Search

The uptake of menadione (2-methyl-1,4-naphthoquinone), which is toxic to yeast cells, and its expulsion as a glutathione complex were studied by scanning electrochemical microscopy. The progression of the in vitro reaction between menadione and glutathione was monitored electrochemically by cyclic voltammetry and correlated with the spectroscopic (UV-visible) behavior. By observing the scanning electrochemical microscope tip current of yeast cells suspended

Janine Mauzeroll; Allen J. Bard

2004-01-01

195

Synthesis and pharmacological activity of diterpenylnaphthoquinone derivatives.  

PubMed

New diterpenylquinones, combining a diterpene diacid and a naphthoquinone, were prepared from junicedric acid and lapachol. The new derivatives were assessed as gastroprotective agents by the HCl-EtOH-induced gastric lesions model in mice as well as for basal cytotoxicity on the following human cell lines: Normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), and hepatocellular carcinoma (Hep G2). Several of the new compounds were significantly active as antiulcer agents and showed selective cytotoxicity against AGS cells. PMID:21996716

Pertino, Mariano Walter; Theoduloz, Cristina; Palenzuela, Jose Antonio; Afonso, Maria del Mar; Yesilada, Erdem; Monsalve, Francisco; González, Paulo; Droguett, Daniel; Schmeda-Hirschmann, Guillermo

2011-01-01

196

HPLC method for the determination of fluvoxamine in human plasma and urine for application to pharmacokinetic studies  

Microsoft Academic Search

A simple, specific and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the assay of fluvoxamine in human plasma and urine. The method was based on reaction of fluvoxamine with 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS) forming orange colored product. The fluvoxamine–NQ derivative was separated by isocratic reversed-phase HPLC and detected at 450nm. The chromatographic conditions were as follows:

Sevgi Tatar Ulu

2007-01-01

197

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

Microsoft Academic Search

Summary 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

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

1993-01-01

198

Desulfurization process for hydrogen sulfide containing gases  

Microsoft Academic Search

A desulfurization process for hydrogen sulfide-containing gases, which comprises contacting an alkaline aqueous medium containing a naphthoquinone sulfonate, a water-soluble compound of at least one polyvalent metal selected from the group consisting of iron, manganese, vanadium and copper, and a water-soluble high molecular compound having weight-average molecular weight of from 300 to 50,000 with a hydrogen sulfide-containing gas thereby causing

T. Sonoda; T. Kaziwara; T. Sato; F. Shimoyama

1984-01-01

199

Novel rearranged abietane diterpenoids from the roots of Salvia sahendica.  

PubMed

Two naphthoquinone diterpenoids, 1 and 2, one tricyclic, and one tetracyclic rearranged abietane ('4,5-seco-10,5-friedo-abietane') diterpenoids, 3 and 4, respectively, together with horminone (5) have been isolated from the roots of Salvia sahendica. Compounds 2 and 3 are new, and the 13C-NMR assignment for compound 4 was modified using ' Heteronuclear Multiple-Bond Correlation' (HMBC) spectroscopic data. The structures of the compounds have been established by using different spectral data including 1D- and 2D-NMR, IR, UV, and MS. The elemental composition for the major peaks of 3 and 4 were determined by ' High-Resolution Electron Impact Mass Spectrometry' (HR-EI-MS). The relative configurations of the new compounds were determined by 1H-NMR and 'Rotating-Frame NOES' (ROESY) spectroscopy. Compounds 1, 2, and 5 showed antifungal activities when tested on Blakeslea trispora. Lapachol, a prelynated naphthoquinone, was used as a positive control. The biological activities of the related naphthoquinones and abietane diterpenoids were discussed. PMID:17193322

Jassbi, Amir Reza; Mehrdad, Morteza; Eghtesadi, Farrokh; Ebrahimi, Samad Nejad; Baldwin, Ian T

2006-08-01

200

Bodipy derivatives as organic triplet photosensitizers for aerobic photoorganocatalytic oxidative coupling of amines and photooxidation of dihydroxylnaphthalenes.  

PubMed

We used iodo-Bodipy derivatives that show strong absorption of visible light and long-lived triplet excited states as organic catalysts for photoredox catalytic organic reactions. Conventionally most of the photocatalysts are based on the off-the-shelf compounds, usually showing weak absorption in the visible region and short triplet excited state lifetimes. Herein, the organic catalysts are used for two photocatalyzed reactions mediated by singlet oxygen ((1)O2), that is, the aerobic oxidative coupling of amines and the photooxidation of dihydroxylnaphthalenes, which is coupled to the subsequent addition of amines to the naphthoquinones, via C-H functionalization of 1,4-naphthoquinone, to produce N-aryl-2-amino-1,4-naphthoquinones (one-pot reaction), which are anticancer and antibiotic reagents. The photoreactions were substantially accelerated with these new iodo-Bodipy organic photocatalysts compared to that catalyzed with the conventional Ru(II)/Ir(III) complexes, which show weak absorption in the visible region and short-lived triplet excited states. Our results will inspire the design and application of new organic triplet photosensitizers that show strong absorption of visible light and long-lived triplet excited state and the application of these catalysts in photoredox catalytic organic reactions. PMID:23668289

Huang, Ling; Zhao, Jianzhang; Guo, Song; Zhang, Caishun; Ma, Jie

2013-06-01

201

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.

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

2013-01-01

202

Deficiency in phylloquinone (vitamin K1) methylation affects prenyl quinone distribution, photosystem I abundance, and anthocyanin accumulation in the Arabidopsis AtmenG mutant.  

PubMed

Phylloquinone (vitamin K(1)) is synthesized in cyanobacteria and in chloroplasts of plants, where it serves as electron carrier of photosystem I. The last step of phylloquinone synthesis in cyanobacteria is the methylation of 2-phytyl-1,4-naphthoquinone by the menG gene product. Here, we report that the uncharacterized Arabidopsis gene At1g23360, which shows sequence similarity to menG, functionally complements the Synechocystis menG mutant. An Arabidopsis mutant, AtmenG, carrying a T-DNA insertion in the gene At1g23360 is devoid of phylloquinone, but contains an increased amount of 2-phytyl-1,4-naphthoquinone. Phylloquinone and 2-phytyl-1,4-naphthoquinone in thylakoid membranes of wild type and AtmenG, respectively, predominantly localize to photosystem I, whereas excess amounts of prenyl quinones are stored in plastoglobules. Photosystem I reaction centers are decreased in AtmenG plants under high light, as revealed by immunoblot and spectroscopic measurements. Anthocyanin accumulation and chalcone synthase (CHS1) transcription are affected during high light exposure, indicating that alterations in photosynthesis in AtmenG affect gene expression in the nucleus. Photosystem II quantum yield is decreased under high light. Therefore, the loss of phylloquinone methylation affects photosystem I stability or turnover, and the limitation in functional photosystem I complexes results in overreduction of photosystem II under high light. PMID:17082184

Lohmann, Antje; Schöttler, Mark Aurel; Bréhélin, Claire; Kessler, Felix; Bock, Ralph; Cahoon, Edgar B; Dörmann, Peter

2006-12-29

203

The Tumor-Selective Cytotoxic Agent ?-Lapachone is a Potent Inhibitor of IDO1  

PubMed Central

?-lapachone is a naturally occurring 1,2-naphthoquinone-based compound that has been advanced into clinical trials based on its tumor-selective cytotoxic properties. Previously, we focused on the related 1,4-naphthoquinone pharmacophore as a basic core structure for developing a series of potent indoleamine 2,3-dioxygenase 1 (IDO1) enzyme inhibitors. In this study, we identified IDO1 inhibitory activity as a previously unrecognized attribute of the clinical candidate ?-lapachone. Enzyme kinetics-based analysis of ?-lapachone indicated an uncompetitive mode of inhibition, while computational modeling predicted binding within the IDO1 active site consistent with other naphthoquinone derivatives. Inhibition of IDO1 has previously been shown to breach the pathogenic tolerization that constrains the immune system from being able to mount an effective anti-tumor response. Thus, the finding that ?-lapachone has IDO1 inhibitory activity adds a new dimension to its potential utility as an anti-cancer agent distinct from its cytotoxic properties, and suggests that a synergistic benefit can be achieved from its combined cytotoxic and immunologic effects.

Flick, Hollie E.; LaLonde, Judith M.; Malachowski, William P.; Muller, Alexander J.

2013-01-01

204

A new approach to evaluating the extent of Michael adduct formation to PAH quinones: tetramethylammonium hydroxide (TMAH) thermochemolysis with GC/MS.  

PubMed

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that are converted to cytotoxic and carcinogenic metabolites, quinones, by detoxifying enzyme systems in animals. PAH metabolites such as the quinones can form Michael adducts with biological macromolecules containing reactive nucleophiles, making detection of exposure to PAHs difficult using conventional techniques. A technique has been developed for detecting exposure to PAHs. Tetramethylammonium hydroxide (TMAH) thermochemolysis coupled with GC/MS is proposed as an assay method for PAH quinones that have formed Michael adducts with biological molecules. Three PAH quinones (1,4-naphthoquinone, 1,2-naphthoquinone, and 1,4-anthraquinone) and 1,4-benzoquinone were reacted with cysteine, and the TMAH thermochemolysis method was used to assay for both thiol and amine adduction between the quinones and the cysteine. Additional studies with 1,4-naphthoquinone adducts to glutathione and bovine serum albumin showed the same thiol and amine TMAH thermochemolysis products with larger peptides as was observed with cysteine adducts. The TMAH GC/MS method clearly shows great promise for detecting PAH quinones, produced by enzymatic conversion of PAHs in biological systems, that have been converted to respective Michael adducts. PMID:14615976

Briggs, Mary K; Desavis, Emmanuel; Mazzer, Paula A; Sunoj, R B; Hatcher, Susan A; Hadad, Christopher M; Hatcher, Patrick G

2003-11-01

205

Inhibitors of human immunodeficiency virus integrase.  

PubMed Central

In an effort to further extend the number of targets for development of antiretroviral agents, we have used an in vitro integrase assay to investigate a variety of chemicals, including topoisomerase inhibitors, antimalarial agents, DNA binders, naphthoquinones, the flavone quercetin, and caffeic acid phenethyl ester as potential human immunodeficiency virus type 1 integrase inhibitors. Our results show that although several topoisomerase inhibitors--including doxorubicin, mitoxantrone, ellipticines, and quercetin--are potent integrase inhibitors, other topoisomerase inhibitors--such as amsacrine, etoposide, teniposide, and camptothecin--are inactive. Other intercalators, such as chloroquine and the bifunctional intercalator ditercalinium, are also active. However, DNA binding does not correlate closely with integrase inhibition. The intercalator 9-aminoacridine and the polyamine DNA minor-groove binders spermine, spermidine, and distamycin have no effect, whereas the non-DNA binders primaquine, 5,8-dihydroxy-1,4-naphthoquinone, and caffeic acid phenethyl ester inhibit the integrase. Caffeic acid phenethyl ester was the only compound that inhibited the integration step to a substantially greater degree than the initial cleavage step of the enzyme. A model of 5,8-dihydroxy-1,4-naphthoquinone interaction with the zinc finger region of the retroviral integrase protein is proposed. Images Fig. 2

Fesen, M R; Kohn, K W; Leteurtre, F; Pommier, Y

1993-01-01

206

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.

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

2013-01-01

207

Sepiapterin reductase mediates chemical redox cycling in lung epithelial cells.  

PubMed

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

2013-06-28

208

The lethal effect of bis-type azridinylnaphthoquinone derivative on oral cancer cells (OEC-M1) associated with anti-apoptotic protein bcl-2  

Microsoft Academic Search

Several drugs of aziridinylbenzoquinone analogs have undergone clinical trials as potential antitumor drugs. These bioreductive compounds are designed to kill tumor cells preferentially within the hypoxic microenvironment. From our previous reported data, it was found that the synthesized 2-aziridin-1-yl-3-[(2-{2-[(3-aziridin-1-yl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)thio]ethoxy}ethyl)thio]naphthoquinone (AZ-1) is a bioreductive compound with potent lethal effect on oral cancer cell, OEC-M1. It was found in this study that

Yi-Chen Peng; Hsien-Shou Kuo; Hsin-Da Tsai; Yu-Ping Yang; Yuh-Ling Lin

2006-01-01

209

Quantum beats of the reaction yield induced by a pulsed microwave field  

NASA Astrophysics Data System (ADS)

The effect of pulsed microwave irradiation on the reaction product has been observed in the photolysis of 2-methyl-1,4-naphthoquinone in a micellar sodium dodecylsulphate solution. Under resonance conditions an increase in the microwave pulse length has resulted in an alternation of the yield of naphthosemiquinone free radicals, due to the periodic population of the reactive singlet state of the radical pair. The singlet-triplet dephasing, induced by long-range interactions between the radicals in the pair, damps the oscillations. The rate constant of this process, obtained from the decrement of the oscillation decay, is (7.1±0.6)×10 7 s -1.

Tadjikov, B. M.; Astashkin, A. V.; Sakaguchi, Y.

1998-02-01

210

Natural product juglone targets three key enzymes from Helicobacter pylori: inhibition assay with crystal structure characterization  

Microsoft Academic Search

Aim:To investigate the inhibition features of the natural product juglone (5-hydroxy-1,4-naphthoquinone) against the three key enzymes from Helicobacter pylori (cystathionine ?-synthase [HpCGS], malonyl-CoA:acyl carrier protein transacylase [HpFabD], and ?-hydroxyacyl-ACP dehydratase [HpFabZ]).Methods:An enzyme inhibition assay against HpCGS was carried out by using a continuous coupled spectrophotometric assay approach. The inhibition assay of HpFabD was performed based on the ?-ketoglutarate dehydrogenase-coupled system,

Yun-hua Kong; Liang Zhang; Zheng-yi Yang; Cong Han; Li-hong Hu; Hua-liang Jiang; Xu Shen

2008-01-01

211

Naphthazarin Protects Against Glutamate-Induced Neuronal Death Via Activation of the Nrf2/ARE pathway  

PubMed Central

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.; Mattson, Mark P.; Camandola, Simonetta

2013-01-01

212

Naphtho[1,2- b]furan-4,5-dione induces apoptosis and S-phase arrest of MDA-MB-231 cells through JNK and ERK signaling activation  

Microsoft Academic Search

Naphtho[1,2-b]furan-4,5-dione (NFD), prepared from 2-hydroxy-1,4-naphthoquinone and chloroacetaldehyde in an efficient one-pot reaction, exhibits anti-carcinogenic effect. The results of present study showed that NFD inhibited the proliferation of breast cancer MDA-MB-231 cells through the induction of S-phase arrest and apoptosis. NFD-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclin A, cyclin B, and cyclin-dependent kinase

Kuei-Li Lin; Jung-Chen Su; Ching-Ming Chien; Chih-Hua Tseng; Yeh-Long Chen; Long-Sen Chang; Shinne-Ren Lin

2010-01-01

213

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

214

Synthesis and cytotoxicity of 6,11-Dihydro-pyrido- and 6,11-Dihydro-benzo[2,3- b]phenazine-6,11-dione derivatives  

Microsoft Academic Search

6,11-Dihydro-pyrido[2,3-b]phenazine-6,11-diones and 6,11-dihydro-benzo[2,3-b]phenazine-6,11-diones were synthesized from 6,7-dichloro-5,8-quinolinedione and 2,3-dichloro-1,4-naphthoquinone. The study on the cytotoxicity on these products revealed that the pyridophenazinediones, tetracyclic heteroquinone analogues with three nitrogen atoms exhibited a high cytotoxicity on several human tumor cell lines. Compound 9c and 9e showed in vitro antitumor activity comparable or superior to doxorubicin against the human ovarian tumor cells (SK-OV-3) and

Young-Shin Kim; Se-Young Park; Hyun-Jung Lee; Myung-Eun Suh; Dieter Schollmeyer; Chong-Ock Lee

2003-01-01

215

Decreased sensitivity to vasoconstrictors in aortic rings after acute exposure to nitric oxide.  

PubMed

Nitric oxide (NO) has been postulated as a regulator of vascular reactivity, and the current study tested the hypothesis that NO-induced decreased sensitivity to vasoconstrictors persists following removal of NO. Endothelium-denuded segments of rat aorta were incubated 2-4 h at 37 degrees C with the NO donor S-nitroso-N-acetylpenicillamine (SNAP). Incubation produced rightward shifts in concentration response curves for phenylephrine [i.e., half-maximum effective concentration (EC50; in microM): control = 0.016, NO = 0.14], aluminum fluoride (i.e., EC50 in mM: control = 1.66, NO = 2.29), and KCl (i.e., EC50 in mM: control = 5.9, NO = 23.9). Similar shifts were seen for two other NO donors. The SNAP-induced shift was not attenuated by a guanylyl cyclase inhibitor, LY-83583 (10 microM) and was not mimicked by 8-bromoguanosine 3',5'-cyclic monophosphate (100 microM). It was attenuated by 1,4-naphthoquinone (50 microM), an inhibitor of endogenous mono-ADP ribosyltransferases. NO incubation increased cGMP content (4.6 +/- 0.8 vs. 1.5 +/- 0.15 pmol/mg protein), an increase unaffected by 1,4-naphthoquinone (3.3 +/- 1.0 pmol/mg protein) but prevented by LY-83583 (1.6 +/- 0.36 pmol/mg protein). ADP ribosylation of three proteins was observed in membranes from HEK 293 cells: 88,66, and 38 kDa. ADP ribosylation of the 38-kDa protein was stimulated in a concentration-dependent manner by NO but was not decreased by 1,4-naphthoquinone. In conclusion, NO produces a long-lasting inhibition of vascular contractility by both a cGMP-dependent and -independent mechanism. Based on the observations of 1,4-naphthoquinone, we conclude that the cGMP-independent mechanism is not stimulation of endogenous ADP ribosylation but some other covalent modification in the pathway that mediates contraction. PMID:8760182

Kanagy, N L; Charpie, J R; Dananberg, J; Webb, R C

1996-07-01

216

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

SciTech Connect

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 [Chemical Sciences Division, S aha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata--700 064 (India)

2008-04-24

217

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

PubMed

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. PMID:23537652

Son, Tae Gen; Kawamoto, Elisa M; Yu, Qian-Sheng; Greig, Nigel H; Mattson, Mark P; Camandola, Simonetta

2013-04-19

218

Derivatives of aminoquinones with N-protected amino acids  

Microsoft Academic Search

Summary  The synthesis of derivatives of aminoquinones with N-protected amino acids is reported here. 2-Amino-1,4-benzoquinone and\\u000a 2-amino-1,4-naphthoquinone, prepared by the azide method in yields of 60 and 95% respectively, were coupled with N-Boc-protected\\u000a amino acids including glycine, serine, proline and tyrosine, to give the correspondening derivatives.N, N?-Diisopropylcarbodiimide\\/1-hydroxybenzotriazole orN, N?-dicyclohexylcarbodiimide\\/HOBt used as coupling reagents provided the expected products in satisfactory yields and

Chrysostomos Pachatouridis; Elias A. Couladouros; Vassilios P. Papageorgiou; Maria Liakopoulou-Kyriakides

1998-01-01

219

Derivatives of Aminoquinones with N-protected Amino Acids  

Microsoft Academic Search

The synthesis of derivatives of aminoquinones with N-protected amino acids is reported here. 2-Amino-1,4-benzoquinone and 2-amino-1,4-naphthoquinone, prepared by the azide method in yields of 60 and 95% respectively, were coupled with N-Boc-protected amino acids including glycine, serine, proline and tyrosine, to give the correspondening derivatives. N,N'-Diisopropylcarbodiimide\\/1-hydroxybenzotriazole or N,N'-dicyclohexylcarbodiimide\\/HOBt used as coupling reagents provided the expected products in satisfactory yields and

Chrysostomos Pachatouridis; Elias A. Couladouros; Vassilios P. Papageorgiou

1998-01-01

220

Thermal and physical properties of flame-retardant epoxy resins containing 2-(6-oxido-6 H-dibenz? c, e??1,2?oxaphosphorin-6-yl)-1,4-naphthalenediol and cured with dicyanate ester  

Microsoft Academic Search

2-(6-oxido-6H-dibenz(c,e)(1,2)oxaphosphorin-6-yl)-1,4-naphthalenediol (DOPONQ) was prepared by the addition reaction of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) with 1,4-naphthoquinone. The phosphorus-containing diol (DOPONQ) was used as a reactive flame retardant by an advancement reaction with the diglycidyl ether of bisphenol-A epoxy (DGEBA) resin at various stoichiometric ratios. DOPONQ-containing advanced epoxy was separately cured with various dicyanate esters to form flame-retardant epoxy\\/cyanate ester systems. The effect of

Tsung-Han Ho; Hann-Jang Hwang; Jeng-Yueh Shieh; Ming-Chin Chung

2008-01-01

221

1H and 13C NMR assignments for two new cordiaquinones from roots of Cordia leucocephala.  

PubMed

From the roots of Cordia leucocephala (Boraginaceae), two new meroterpenoid naphthoquinones, 6-[10-(12,12-dimethyl-13alpha-hydroxy-16-methenyl-cyclohexyl)ethyl]-1,4-naphthalenedione (cordiaquinone L) and 5-methyl-6-[10-(12,12-dimethyl-13beta-hydroxy-16-methenyl-cyclohexyl)methyl-1,4-naphthalenedione (cordiaquinone M) were isolated. Their structures were elucidated after detailed 1D and 2D NMR (COSY, HSQC, HMBC and NOESY) data analyses and comparison with literature data for analogous compounds. PMID:19025970

Diniz, Jaécio Carlos; Viana, Francisco Arnaldo; Oliveira, Odaci Fernandes; Maciel, Maria Aparecida M; Torres, Maria da Conceição de Menezes; Braz-Filho, Raimundo; Silveira, Edilberto R; Pessoa, Otília Deusdênia L

2009-02-01

222

Pigment Cell Differentiation in Sea Urchin Blastula-Derived Primary Cell Cultures  

PubMed Central

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.

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

2014-01-01

223

Investigating PAH relative reactivity using congener profiles, quinone measurements and back trajectories  

NASA Astrophysics Data System (ADS)

Vapour and particle-associated concentrations of 15 polycyclic aromatic hydrocarbons (PAH) and 11 PAH quinones have been measured in winter and summer campaigns at the rural site, Weybourne in eastern England. Concentrations of individual PAH are 20-140 times smaller than average concentrations at an English urban site. The concentrations of PAH are greatest in air masses originating from southern England relative to those from Scandinavia and the North Atlantic, while quinone to parent PAH ratios show an inverse behaviour, being highest in the more aged North Atlantic polar air masses. While concentration of 1,2-naphthoquinone decline from summer to winter, those of 1,4-naphthoquinone and anthraquinone increase suggesting a photochemical formation pathway. A comparison of congener concentration profiles measured at Weybourne with those from an urban source area (Birmingham) reveals differential losses at the rural site, especially evident in fluoranthene: pyrene ratios and consistent with the known rates of vapour phase reactions of 3 and 4 ring compounds with hydroxyl radical. The ratios of quinones to their parent PAH at Weybourne are greater than those in the urban source area indicating either more rapid loss processes for PAH, or formation of quinones during advection of the air mass, or probably both.

Alam, M. S.; Delgado-Saborit, J. M.; Stark, C.; Harrison, R. M.

2013-10-01

224

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

225

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

2014-01-01

226

PHTHIOCOL AND MENADIONE AS ACETATE-REPLACING FACTORS FOR LACTOBACILLUS DELBRUECKII  

PubMed Central

MaciasR, Frank M. (Northrop Corporation, Hawthorne, Calif.). Phthiocol and menadione as acetate-replacing factors for Lactobacillus delbrueckii. J. Bacteriol. 82:657–661. 1961.—Lactobacillus delbrueckii (ATCC 9649), when cultured under nitrogen, or in ferrous iron-containing media exposed to air, requires, for the initiation of growth, compounds that are known to behave as electron acceptors. The ferrous iron probably induces what amounts to anaerobic conditions; that is, it blocks access of the organism to oxygen. Several electron carriers, such as methylene blue and naphthoquinones, stimulate growth of the organism in acetate-free media exposed to air. The most active acetate-replacing agent found is phthiocol. Methylene blue does not stimulate growth under nitrogen. It is suggested that the naphthoquinones bring about the initial oxidations required for growth by transferring the electrons to some other constituent of the medium. Growth of the organism in acetate-free media under CO2 indicates that CO2 or its fixation product can behave also as an initial oxidant.

MaciasR, Frank M.

1961-01-01

227

Redox and non-redox mechanism of in vitro cyclooxygenase inhibition by natural quinones.  

PubMed

In this study, ten anthra-, nine naphtho-, and five benzoquinone compounds of natural origin and five synthetic naphthoquinones were assessed, using an enzymatic in vitro assay, for their potential to inhibit cyclooxygenase-1 and -2 (COX-1 and COX-2), the key enzymes of the arachidonic acid cascade. IC?? values comparable with COX reference inhibitor indomethacin were recorded for several quinones (primin, alkannin, diospyrin, juglone, 7-methyljuglone, and shikonin). For some of the compounds, we suggest the redox potential of quinones as the mechanism responsible for in vitro COX inhibition because of the quantitative correlation with their pro-oxidant effect. Structure-relationship activity studies revealed that the substitutions at positions 2 and 5 play the key roles in the COX inhibitory and pro-oxidant actions of naphthoquinones. In contrast, the redox mechanism alone could not explain the activity of primin, embelin, alkannin, and diospyrin. For these four quinones, molecular modeling suggested similar binding modes as for conventional nonsteroidal anti-inflammatory drugs (NSAIDs). PMID:22174077

Landa, Premysl; Kutil, Zsofia; Temml, Veronika; Vuorinen, Anna; Malik, Jan; Dvorakova, Marcela; Marsik, Petr; Kokoska, Ladislav; Pribylova, Marie; Schuster, Daniela; Vanek, Tomas

2012-03-01

228

Selective and slow-binding inhibition of shikonin derivatives isolated from Lithospermum erythrorhizon on glycosyl hydrolase 33 and 34 sialidases.  

PubMed

Sialidases are enzymes that catalyze the hydrolysis of sialic acid residues from various glycoconjugates, which are widely found in a number of viral and microbial pathogens. In this study, we investigated the biological evaluation of isolated six shikonins (1-6) and three shikonofurans (7-9) from Lithospermum erythrorhizon. The nine isolated compounds 1-9 showed strong and selective inhibition of glycosyl hydrolase (GH) 33 and -34 sialidases activities. In GH33 bacterial-sialidase inhibition assay, the inhibitory activities against GH33 siadliase of all shikonofuran derivatives (7-9) were greater than shikonin derivatives (1-6). Shikonofuran E (8) exhibited the most potent inhibitory activity toward GH33 sialidases (IC(50)=0.24?M). Moreover, our detailed kinetic analysis of these species unveiled that they are all competitive and simple reversible slow-binding inhibitors. Otherwise, they showed different inhibitory capacities and kinetic modes to GH34 viral-sialidase activity. All the naphthoquinone derivatives (1-6) were of almost equal efficiency with IC(50) value of 40?M and shikonofurans (7-9) did not show the significant inhibitory effect to GH34 sialidase. Kinetic analyses indicated that naphthoquinones acted via a noncompetitive mechanism. PMID:22300884

Kim, Ji Young; Jeong, Hyung Jae; Park, Ji-Young; Kim, Young Min; Park, Su-Jin; Cho, Jung Keun; Park, Ki Hun; Ryu, Young Bae; Lee, Woo Song

2012-03-01

229

Effects of Atovaquone and Diospyrin-Based Drugs on Ubiquinone Biosynthesis in Pneumocystis carinii Organisms  

PubMed Central

The naphthoquinone atovaquone is effective against Plasmodium and Pneumocystis carinii carinii. In Plasmodium, the primary mechanism of drug action is an irreversible binding to the mitochondrial cytochrome bc1 complex as an analog of ubiquinone. Blockage of the electron transport chain ultimately inhibits de novo pyrimidine biosynthesis since dihydroorotate dehydrogenase, a key enzyme in pyrimidine biosynthesis, is unable to transfer electrons to ubiquinone. In the present study, the effect of atovaquone was examined on Pneumocystis carinii carinii coenzyme Q biosynthesis (rather than electron transport and respiration) by measuring its effect on the incorporation of radiolabeled p-hydroxybenzoate into ubiquinone in vitro. A triphasic dose-response was observed, with inhibition at 10 nM and then stimulation up to 0.2 ?M, followed by inhibition at 1 ?M. Since other naphthoquinone drugs may also act as analogs of ubiquinone, diospyrin and two of its derivatives were also tested for their effects on ubiquinone biosynthesis in P. carinii carinii. In contrast to atovaquone, these drugs did not inhibit the incorporation of p-hydroxybenzoate into P. carinii carinii ubiquinone.

Kaneshiro, Edna S.; Sul, Donggeun; Hazra, Banasri

2000-01-01

230

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

231

Synergistic TRAIL sensitizers from Barleria alluaudii and Diospyros maritima#  

PubMed Central

Barleria alluaudii and Diospyros maritima were both investigated as part of an ongoing search for synergistic TRAIL (tumor necrosis factor-?-related apoptosis-inducing ligand) sensitizers. As a result of this study, two naphthoquinone epoxides, 2,3-epoxy-2,3-dihydrolapachol (1) and 2,3-epoxy-2,3-dihydro-8-hydroxylapachol (2), both not previously isolated from natural sources, and the known 2-methyl anthraquinone (3) were identified from B. alluaudii. Time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra were utilized to establish the absolute configuration of 1 and 2. Additionally, five known naphthoquinone derivatives, maritinone (4), elliptinone (5), plumbagin (6), (+)-cis-isoshinanolone (7), and ethylidene-6,6?-biplumbagin (8) were isolated from D. maritima. Compounds 1, 2, and 4–6 showed varying levels of synergy with TRAIL. Maritinone (4) and elliptinone (5) showed the highest synergistic effect, with more than a three-fold increase in activity observed with TRAIL than with compound alone.

Whitson, Emily L.; Sun, Han; Thomas, Cheryl L.; Henrich, Curtis J.; Sayers, Thomas J.; McMahon, James B.; Griesinger, Christian; McKee, Tawnya C.

2012-01-01

232

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

233

Inhibitory effect of liposomal rhinacanthin-N isolated from Rhinacanthus nasutus on pulmonary metastasis in mice.  

PubMed

We previously observed that rhinacanthins, which are the main naphthoquinone esters isolated from the roots of a Thai medicinal plant, Rhinacanthus nasutus KURZ. (family Acanthaceae), suppress the growth of Meth-A sarcoma in the tumor-bearing mice and that rhinacanthin-N has the strongest antitumor activity among these naphthoquinone esters tested. In the present study, we investigated the effect of rhinacanthin-N on pulmonary metastasis induced by B16F10 melanoma cells in mice. C57BL/6 male mice were injected intravenously with B16F10 melanoma cells, and liposomal rhinacanthin-N was administered intraperitoneally from day 1 to 7 after tumor implantation. Liposomes were used to formulate an injectable form of the hydrophobic agent. Treatment of the mice with 5 or 10?mg/kg/d of liposomal rhinacanthin-N significantly inhibited the pulmonary metastatic colonization of the melanoma cells. Based on these data, our findings demonstrate that rhinacanthin-N possesses antimetastatic efficacy, which may make it a lead compound for the development of a new anticancer drug for use in cancer chemotherapy. PMID:22791173

Siripong, Pongpun; Yahuafai, Jantana; Piyaviriyakul, Suratsawadee; Kanokmedhakul, Kwanjai; Koide, Hiroyuki; Ishii, Takayuki; Shimizu, Kosuke; Ruchirawat, Somsak; Oku, Naoto

2012-01-01

234

Inhibition of in vitro leukotriene B4 biosynthesis in human neutrophil granulocytes and docking studies of natural quinones.  

PubMed

Quinones are compounds frequently contained in medicinal plants used for the treatment of inflammatory diseases. Therefore, the impact of plant-derived quinones on the arachidonic acid metabolic pathway is worthy of investigation. In this study, twenty-three quinone compounds of plant origin were tested in vitro for their potential to inhibit leukotriene B4 (LTB4) biosynthesis in activated human neutrophil granulocytes with 5-lipoxygenase (5-LOX) activity. The benzoquinones primin (3) and thymohydroquinone (4) (IC50 = 4.0 and 4.1 microM, respectively) showed activity comparable with the reference inhibitor zileuton (1C50 = 4.1 microM). Moderate activity was observed for the benzoquinone thymoquinone (2) (1C50 = 18.2 microM) and the naphthoquinone shikonin (1) (IC50 = 24.3 microM). The anthraquinone emodin and the naphthoquinone plumbagin (5) displayed only weak activities (IC50 > 50 microM). The binding modes of the active compounds were further evaluated in silico by molecular docking to the human 5-LOX crystal structure. This process supports the biological data and suggested that, although the redox potential is responsible for the quinone's activity on multiple targets, in the case of 5-LOX the molecular structure plays a vital role in the inhibition. The obtained results suggest primin as a promising compound for the development of dual COX-2/5-LOX inhibitors. PMID:23472470

Landa, Premysl; Kutil, Zsofia; Temml, Veronika; Malik, Jan; Kokoska, Ladislav; Widowitz, Ute; Pribylova, Marie; Dvorakova, Marcela; Marsik, Petr; Schuster, Daniela; Bauer, Rudolf; Vanek, Tomas

2013-01-01

235

Quinone-carbohydrate nonglucoside conjugates as a new type of cytotoxic agents: synthesis and determination of in vitro activity.  

PubMed

We have found that 2-methoxy-1,4-naphthoquinones easily react with primary alcohols to produce the corresponding 2-alkoxyderivatives. Using this reaction, we synthesized methyl-6-O-(naphthalene-1,4-dione-2-yl)-?-D-glucopyranosides, a new type of water soluble quinone-carbohydrate nonglucoside conjugates. The resulting conjugates induced apoptosis in human cancer HeLa and normal mouse JB6 P(+) Cl41 cells with simultaneous inhibition of p53-dependant transcriptional activity, suggesting that the observed cell death was p53-independent. Furthermore, we analyzed structure-activity relationship and bioactivity of 2-hydroxy- and 2-methoxy-1,4-naphthoquinones as well as carbohydrate nonglucoside conjugates. All compounds containing a quinone moiety were able to inhibit p53-dependant transcriptional activity and exerted moderate inhibitory effects on HeLa cell colony formation. Investigations of structure-activity relationships revealed that cytotoxicity depended on the type of substituent at C-2 of the quinone moiety, decreasing in the following order: methoxyderivatives > carbohydrate nonglucoside conjugates > hydroxyderivatives. Furthermore, cytotoxicity depended on the position of the hydroxy substituent in the quinone moiety in all derivatives and decreased in the following order: 8- > 5- > 5,8-derivatives. In conclusion, this is the first report on synthesis and biological structure-activity relationships of the new class of quinone-carbohydrate nonglucoside conjugates. PMID:24631733

Pelageev, Dmitry N; Dyshlovoy, Sergey A; Pokhilo, Nataly D; Denisenko, Vladimir A; Borisova, Ksenia L; Keller-von Amsberg, Gunhild; Bokemeyer, Carsten; Fedorov, Sergey N; Honecker, Friedemann; Anufriev, Victor Ph

2014-04-22

236

Improved understanding of bimolecular reactions in deceptively simple homogeneous media: From laboratory experiments to Lagrangian quantification  

NASA Astrophysics Data System (ADS)

heterogeneity affects reaction kinetics by controlling the mixing of reactant particles, but the linkage between medium properties and reaction kinetics is difficult to build, even for simple, relatively homogeneous media. This study aims to explore the dynamics of bimolecular reactions, aniline + 1,2-naphthoquinone-4-sulfonic acid ? 1,2-naphthoquinone-4-aminobenzene, in relatively homogeneous flow cells. Laboratory experiments were conducted to monitor the transport of both conservative and reactive tracers through columns packed with silica sand of specific diameters. The measured tracer breakthrough curves exhibit subdiffusive behavior with a late-time tail becoming more pronounced with decreasing sand size, probably due to the segregated flow regions formed more easily in columns packed with smaller size sand. Numerical analysis using a novel Lagrangian model shows that subdiffusion has a twofold effect on bimolecular reactions. While subdiffusion enhances the power-law growth rate of product mass by prolonging the exposure of reactant particles in the depletion zone, the global reaction rate is constrained because subdiffusion constrains the mobility of reactant particles. Reactive kinetics in deceptively simple homogeneous media is therefore controlled by subdiffusion, which is sensitive to the dimensions of packed sand.

Zhang, Yong; Qian, Jiazhong; Papelis, Charalambos; Sun, Pengtao; Yu, Zhongbo

2014-02-01

237

Synergistic TRAIL sensitizers from Barleria alluaudii and Diospyros maritima.  

PubMed

Barleria alluaudii and Diospyros maritima were both investigated as part of an ongoing search for synergistic TRAIL (tumor necrosis factor-?-related apoptosis-inducing ligand) sensitizers. As a result of this study, two naphthoquinone epoxides, 2,3-epoxy-2,3-dihydrolapachol (1) and 2,3-epoxy-2,3-dihydro-8-hydroxylapachol (2), both not previously isolated from natural sources, and the known 2-methylanthraquinone (3) were identified from B. alluaudii. Time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra were utilized to establish the absolute configuration of 1 and 2. Additionally, five known naphthoquinone derivatives, maritinone (4), elliptinone (5), plumbagin (6), (+)-cis-isoshinanolone (7), and ethylidene-6,6'-biplumbagin (8), were isolated from D. maritima. Compounds 1, 2, and 4-6 showed varying levels of synergy with TRAIL. Maritinone (4) and elliptinone (5) showed the highest synergistic effect, with more than a 3-fold increase in activity observed with TRAIL than with compound alone. PMID:22313254

Whitson, Emily L; Sun, Han; Thomas, Cheryl L; Henrich, Curtis J; Sayers, Thomas J; McMahon, James B; Griesinger, Christian; McKee, Tawnya C

2012-03-23

238

Naphthazarin has a protective effect on the 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson's disease model.  

PubMed

"Neurohormesis" refers to a response to a moderate level of stress that enhances the ability of the nervous systems to resist more severe stress that might be lethal or cause dysfunction or disease. Neurohormetic phytochemicals, such as, resveratrol, sulforaphane, curcumin, and catechins, protect neurons against injury and disease. Naphthoquinones, such as, juglone and plumbagin, induce robust hormetic stress responses. However, the possibility that subtoxic dose of 5,8-dihydroxy-1,4-naphthoquinone (naphthazarin) may protect against brain diseases via the activation of an adaptive stress response pathway in the brain has not been investigated. In this study, we examined the neurohormetic effect of a subtoxic dose of naphthazarin in a Parkinson's disease model. It was found that, under these conditions, naphthazarin enhanced movement ability, prevented loss of dopaminergic neurons, and attenuated neuroinflammation in a 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson's disease model. Furthermore, it was found that the neuroprotective effect of naphthazarin was mediated by the suppression of astroglial activation in response to 1-methyl-4-phenylpyridine treatment. In conclusion, we suggest that naphthazarin, in view of its hormetic effect on neuroprotection, be viewed as a potential treatment for Parkinson's disease and other neurodegenerative diseases associated with neuroinflammation. PMID:22513651

Choi, Seon Young; Son, Tae Gen; Park, Hee Ra; Jang, Young Jung; Oh, Shin Bi; Jin, Bora; Lee, Jaewon

2012-09-01

239

Anticancer compound plumbagin and its molecular targets: a structural insight into the inhibitory mechanisms using computational approaches.  

PubMed

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a naphthoquinone derivative from the roots of plant Plumbago zeylanica and belongs to one of the largest and diverse groups of plant metabolites. The anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin exerts inhibitory effects on multiple cancer-signaling proteins, however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. The present study is the first attempt to provide structural insights into the binding mode of plumbagin to five cancer signaling proteins viz. PI3K?, AKT1/PKB?, Bcl-2, NF-?B, and Stat3 using molecular docking and (un)binding simulation analysis. We validated plumbagin docking to these targets with previously known important residues. The study also identified and characterized various novel interacting residues of these targets which mediate the binding of plumbagin. Moreover, the exact modes of inhibition when multiple mode of inhibition existed was also shown. Results indicated that the engaging of these important interacting residues in plumbagin binding leads to inhibition of these cancer-signaling proteins which are key players in the pathogenesis of cancer and thereby ceases the progression of the disease. PMID:24586269

Jamal, Mohammad S; Parveen, Shadma; Beg, Mohd A; Suhail, Mohd; Chaudhary, Adeel G A; Damanhouri, Ghazi A; Abuzenadah, Adel M; Rehan, Mohd

2014-01-01

240

Indothiazinone, an indolyl thiazolyl ketone from a novel myxobacterium belonging to the Sorangiineae.  

PubMed

Indothiazinone (1), an indolyl thiazolyl ketone, was discovered in cultures of novel myxobacterial strain 706, recently isolated from compost in Germany. Molecular phylogenetic studies based on 16S rRNA gene sequences revealed strain 706 to be a representative of a new family of the Sorangiineae. A screening of the culture broth for antimicrobial metabolites followed by isolation and characterization of these compounds revealed six indole derivatives and a 1,4-naphthoquinone derivative. The structures were determined to be indothiazinone (1; 1H-indol-3-yl(1,3-thiazol-2-yl)methanone) and three 3-methylbuta-1,3-dien-1-yl-substituted indoles, indolyl ethanol 2 and the E- and Z-isomers of indolyl ethylidenehydroxylamine 4 and 5 by MS and NMR spectroscopic analyses. In the indolyl ethanol derivative 3 the unsaturated methylene group of the butadienyl residue was replaced by an oxygen atom to give the keto group of the butanone side chain. Further 1H-indol-3-ylacetonitrile (6) was identified, which was already known as a myxobacterial metabolite. 2-Hydroxyethyl-3-methyl-1,4-naphthoquinone (7) was recognized during dereplication as an antibiotic previously isolated from Actinoplanes capillaceus. Whereas 1, 4, 5, and 7 showed weak activity against yeasts and filamentous fungi, isomers 4 and 5 were weakly active against Gram-positive bacteria and mouse fibroblasts. Compound 6 is volatile, and 2 and 3 showed no activity in a number of assays. PMID:24697522

Jansen, Rolf; Mohr, Kathrin I; Bernecker, Steffen; Stadler, Marc; Müller, Rolf

2014-04-25

241

Selective growth-inhibiting effects of compounds identified in Tabebuia impetiginosa inner bark on human intestinal bacteria.  

PubMed

The growth-inhibiting activity of anthraquinone-2-carboxylic acid and lapachol identified in the inner bark of taheebo, Tabebuia impetiginosa, toward 10 human intestinal bacteria was evaluated by using a paper disk diffusion bioassay and compared to those of seven lapachol congeners (1,4-naphthoquinone, naphthazarin, menadione, lawsone, plumbagin, juglone, and dichlone) as well as two commercially available antibiotics, chloramphenicol and tetracycline. Anthraquinone-2-carboxylic acid exhibited very strong growth inhibition of Clostridium paraputrificum at 1 microg/disk while 100 microg/disk of lapachol was needed for moderate growth inhibition of the same organism. These two isolates exhibited weak inhibition of Clostridium perfringens and Escherichia coli at 100 microg/disk while no adverse effects were observed on the growth of Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium infantis, Lactobacillus acidophilus, and Lactobacillus casei at 1000 microg/disk. Structure-activity relationships indicate that a methyl group in the C-2 position of 1,4-naphthoquinone derivatives might play an important role in antibacterial activity. PMID:15713033

Park, Byeoung-Soo; Kim, Jun-Ran; Lee, Sung-Eun; Kim, Kyoung Soon; Takeoka, Gary R; Ahn, Young-Joon; Kim, Jeong-Han

2005-02-23

242

Investigating PAH relative reactivity using congener profiles, quinone measurements and back trajectories  

NASA Astrophysics Data System (ADS)

Vapour and particle-associated concentrations of 15 polycyclic aromatic hydrocarbons (PAH) and 11 PAH quinones have been measured in winter and summer campaigns at the rural site, Weybourne in eastern England. Concentrations of individual PAH are relatively smaller than average concentrations measured previously at urban sites in the UK. The concentrations of PAH of the air masses originating from southern England and mainland UK are significantly larger than those from Eastern Europe and the North Atlantic, while quinone to parent PAH ratios show an inverse behaviour, being highest in the more aged North Atlantic polar air masses. While concentrations of 1,2-naphthoquinone decline from winter to summer, those of 1,4-naphthoquinone and anthraquinone increase suggesting a photochemical formation pathway. A comparison of congener concentration profiles measured at Weybourne with those from an urban source area (Birmingham) reveals differential losses at the rural site, especially evident in fluoranthene : pyrene ratios and consistent with the known rates of vapour phase reactions of 3 and 4 ring compounds with hydroxyl radical. The ratios of quinones to their parent PAH at Weybourne are greater than those in the urban source area indicating either more rapid loss processes for PAH, or formation of quinones during advection of the air mass, or probably both.

Alam, M. S.; Delgado-Saborit, J. M.; Stark, C.; Harrison, R. M.

2014-03-01

243

o-PHENANTHROLINE AND DERIVATIVES OF VITAMIN K AS STABILIZERS OF PHOTOREDUCTION IN SCENEDESMUS.  

PubMed

It is known that with increasing concentrations of hydroxylamine the rate of photoreduction in the alga Scenedesmus drops to about one-half of the normal rate. From then on photoreduction remains insensitive to hydroxylamine. The present experiments prove that this strange effect is not specific for hydroxylamine. It can be produced with substances having quite different chemical properties, such as o-phenanthroline, 2-methyl-1,4-naphthoquinone (vitamin K), or 2-oxy-3-methyl-naphthoquinone (phthiocol). Once the rate of photoreduction has been brought down to the limit of exactly one-half by a sufficient dose of any one of these substances, the reaction is also stabilized against reversion under the influence of strong light. At saturation intensities the rate of the stabilized photoreduction may be several times that at which the unpoisoned cells revert to photosynthesis. The ratio of one-half between the rates of the stabilized and the normal photoreduction is found at very low light intensities. This indicates a change in the photochemical process. Since the assimilatory quotient remains unaltered, it is the quantum yield which is cut in half under the influence of the poisons. To explain these observations it is assumed that either just one-half of the primary photoproducts are lost, or that they react back entirely while causing a reduction of carbon dioxide in a way similar to that brought about by the oxyhydrogen reaction in the dark. PMID:19873420

Gaffron, H

1945-01-20

244

SOME EFFECTS OF DERIVATIVES OF VITAMIN K ON THE METABOLISM OF UNICELLULAR ALGAE.  

PubMed

Vitamin K(1), 2-methyl-3-phytyl-1,4-naphthoquinone, is a substance found in all plant chloroplasts. It is, therefore, interesting to know whether it has any influence upon the metabolism of plants. Experiments made with the phytol-free derivatives like 2-methyl-1,4-naphthoquinone or the corresponding 3-oxy compound, phthiocol, gave the following results. These substances accelerate the respiration of Chlorella or Scenedesmus in a way similar to the action of the dinitrophenols. They inhibit photosynthesis and the compensation of respiration in the light strongly like hydroxylamine. In Scenedesmus they hinder the adaptation to the anaerobic utilization of hydrogen. If given after adaptation in amounts sufficient to stop photosynthesis they do not prevent photoreduction but rather stabilize this reaction against reversion. Their presence destroys the coupling between the reduction of carbon dioxide in the dark and the oxyhydrogen reaction in adapted algae. One can expect, therefore, that the natural vitamin K present in plants in concentrations of about 10(-3)M takes part in some metabolic reaction as a catalyst or regulator. PMID:19873419

Gaffron, H

1945-01-20

245

Effects of different quinoid redox mediators on the simultaneous removal of p-cresol and sulphide in a denitrifying process.  

PubMed

The catalytic effects of different quinoid redox mediators (RM) on the simultaneous removal of sulphide and p-cresol in a denitrifying process were evaluated in batch studies. 2-Hydroxy-1,4-naphthoquinone (LAW) and anthraquinone-2,6-disulphonate (AQDS) did not significantly affect the sulphide oxidation rate, which, in contrast, was increased 14% in the presence of 1,2-naphthoquinone-4-sulphonate (NQS). The input of NQS on the oxidation of sulphide was also favourably reflected in a 13% higher sulphate production. All RM promoted a higher (up to 34% compared to the control lacking RM) degree of mineralization of p-cresol. LAW also supported a 47% higher denitrifying yield (Y(N2)), compared to the control lacking quinones. Nevertheless, AQDS and NQS decreased the Y(N2) by 12-13%. Our results suggest that a proper scrutiny should be conducted before deciding the sort of quinone to be applied in denitrifying processes. The heterogeneous effects observed also advise to consider both the respiratory rates and the yields as important parameters for deciphering the impact of RM on denitrifying processes. PMID:19474488

Meza-Escalante, Edna R; Texier, Anne-Claire; Cuervo-López, Flor; Gómez, Jorge; Cervantes, Francisco J

2009-01-01

246

Quantum mechanical/molecular mechanical modeling finds Diels-Alder reactions are accelerated less on the surface of water than in water.  

PubMed

Quantum and molecular mechanics calculations for the Diels-Alder reactions of cyclopentadiene with 1,4-naphthoquinone, methyl vinyl ketone, and acrylonitrile have been carried out at the vacuum-water interface and in the gas phase. In conjunction with previous studies of these cycloadditions in dilute solution, a more complete picture of aqueous environmental effects emerges with implications for the origin of observed rate accelerations using heterogeneous aqueous suspensions, "on water" conditions. The pure TIP4P water slab maintains the bulk density and hydrogen-bonding properties in central water layers. The bulk region merges to vacuum over a ca. 5 A band with progressive diminution of the density and hydrogen bonding. The relative free energies of activation and transition structures for the reactions at the interface are found to be intermediate between those calculated in the gas phase and in bulk water; i.e., for the reaction with 1,4-naphthoquinone, the DeltaDeltaG(++) values relative to the gas phase are -3.6 and -7.3 kcal/mol at the interface and in bulk water, respectively. Thus, the results do not support the notion that a water surface is more effective than bulk water for catalysis of such pericyclic reactions. The trend is in qualitative agreement with expectations based on density considerations and estimates of experimental rate constants for the gas phase, a heterogeneous aqueous suspension, and a dilute aqueous solution for the reaction of cyclopentadiene with methyl vinyl ketone. Computed energy pair distributions reveal a uniform loss of 0.5-1.0 hydrogen bond for the reactants and transition states in progressing from bulk water to the vacuum-water interface. Orientational effects are apparent at the surface; e.g., the carbonyl group in the methyl vinyl ketone transition structure is preferentially oriented into the surface. Also, the transition structure for the 1,4-naphthoquinone case is buried more in the surface, and the free energy of activation for this reaction is most similar to the result in bulk water. PMID:20148559

Thomas, Laura L; Tirado-Rives, Julian; Jorgensen, William L

2010-03-10

247

QM/MM Modeling Finds Diels-Alder Reactions are Accelerated Less On the Surface of Water than In Water  

PubMed Central

Quantum and molecular mechanics (QM/MM) calculations for the Diels-Alder reactions of cyclopentadiene with 1,4-naphthoquinone, methyl vinyl ketone, and acrylonitrile have been carried out at the vacuum-water interface and in the gas phase. In conjunction with previous studies of these cycloadditions in dilute solution, a more complete picture of aqueous environmental effects emerges with implications for the origin of observed rate accelerations using heterogeneous aqueous suspensions, “on water” conditions. The pure TIP4P water slab maintains bulk density and hydrogen bonding properties in central water layers. The bulk region merges to vacuum over a ca. 5-Å band with progressive diminution of density and hydrogen bonding. The relative free energies of activation and transition structures for the reactions at the interface are found to be intermediate between those calculated in the gas phase and in bulk water, i.e., for the reaction with 1,4-naphthoquinone, the ??G ‡’s relative to the gas phase are ?3.6 and ?7.3 kcal/mol at the interface and in bulk water, respectively. Thus, the results do not support the notion that a water surface is more effective than bulk water for catalysis of such pericyclic reactions. The trend is in qualitative agreement with expectations based on density considerations and estimates of experimental rate constants for the gas phase, a heterogeneous aqueous suspension, and dilute aqueous solution for the reaction of cyclopentadiene with methyl vinyl ketone. Computed energy pair distributions reveal a uniform loss of 0.5 – 1.0 hydrogen bond for the reactants and transition states in progressing from bulk water to the vacuum-water interface. Orientational effects are apparent at the surface, e.g., the carbonyl group in the methyl vinyl ketone transition structure is preferentially oriented into the surface. Also, the transition structure for the 1,4-naphthoquinone case is buried more in the surface, and the free energy of activation for this reaction is most similar to the result in bulk water.

Thomas, Laura L.; Tirado-Rives, Julian; Jorgensen, William L.

2010-01-01

248

Abiotic transformation of catechol and 1-naphthol in aqueous solution-influence of environmental factors.  

PubMed

The abiotic transformation of catechol and 1-naphthol singly and in mixtures was tested in sterile Tris-HCl buffer with regard to several environmental factors including temperature (7 degrees C, 20 degrees C and 30 degrees C), lighting conditions, pH (between 7.0 and 8.5) and dissolved oxygen (at partial pressures of 0.0, 220, 2200, 11000 and 22000 Pa). Irrespective of lighting conditions. catechol autoxidation was confirmed in aerated medium with a rate independent of the presence of 1-naphthol but proportional to the dissolved oxygen concentration, to the pH (its half-disappearance occurred in 24h at pH 8.5) and, to a lesser extent, to the incubating temperature (at 20 degrees C, 20% disappeared in 10 days at pH 7.0). Under alkaline conditions, the reaction of the anionic form (catecholate) with an equimolar concentration of molecular oxygen (O2) led presumably to hydrogen peroxide anion (HO2-) and coloured polymerization products. When tested alone, 1-naphthol was not significantly influenced either by lighting conditions, incubating temperature or dissolved oxygen concentration. It was also found to be quite stable with respect to pH, with a 15-fold weaker transformation rate than for catechol at the highest pH used. When tested in a mixture with catechol, 1-naphthol was found to be involved in a new chemical oxidation reaction catalyzed by catecholate. The transformation of one mole of 1-naphthol consumes four moles of oxygen. In the presence of catechol, the stoichiometry of the 1-naphthol transformation, under the influence of oxygen, suggests the possible formation of 2,5,6,8-tetrahydroxy 1,4-naphthoquinone via Lawsone (2-hydroxy 1,4-naphthoquinone) and naphthopurpurine (2,5,8-trihydroxy 1,4-naphthoquinone) as hypothetic intermediates. This is the first report of the autoxidation of 1-naphthol, catalyzed by catechol, in aqueous solution, in the absence of UV irradiation. PMID:11561636

Borraccino, R; Kharoune, M; Giot, R; Agathos, S N; Nyns, E J; Naveau, H P; Pauss, A

2001-10-01

249

A mechanistic examination of redox cycling activity in carbonaceous particulate matter  

NASA Astrophysics Data System (ADS)

Mechanistic aspects of carbonaceous aerosol toxicity were examined with respect to the ability of particles to catalyse reactive oxygen species-generating redox cycling reactions. To investigate the role of secondary organic material, we examined two systems. In the first, two-stroke engine exhaust particles were found to increase their ability to catalyse redox cycling in the presence of a reducing agent, dithiothreitol (DTT), when the exhaust was exposed to ozone. This occurred through deposition of redox-active secondary organic aerosol (SOA) onto the particle that was ten times more redox active per microgram than the primary engine particle. In the second system, naphthalene SOA formed highly redox active particles. Activity was strongly correlated to the amount of the 1,4- and 1,2-naphthoquinone measured in the particle phase. However, these species and the newly quantified naphthalene oxidation product 5-hydroxy-1,4-naphthoquinone accounted for only 30% of the observed DTT decay from the particles. Gas-particle partitioning coefficients suggest 1,4- and 1,2- naphthoquinone are not strong contributors to ambient particle redox activity at 25 °C. However, a large number of redox active species are unidentified. Some of these may be highly oxidised products of sufficiently low vapour pressure to be atmospherically relevant. DTT activity of diesel particles was found to be high per unit mass. The activity was found to be associated with the insoluble fraction as filtration of the particles nearly eliminated DTT decay. Neither methanol nor dichloromethane extracts of diesel particles exhibited redox activity, indicating that the redox active species are associated with the black carbon portion of the particles. Examination of particle concentration techniques found that use of water condensation to grow and concentrate particles introduced a large organic artefact to the particles. Experiments with concentrated inorganic particles suggest that the source of this artefact is from irreversible uptake of water-soluble volatile organic compounds. Overall, carbonaceous redox active species can be thought of as a continuum from small, water-soluble species to redox active functionalities on elemental carbon backbones. In addition to clearly defined, quantifiable species, future research may need to consider examining broader chemical classes or redox-active chemical functionalities to overcome the inherent complexity of these constituents.

McWhinney, Robert David

250

Lithium and Indium Quinoneoximic Complexes and Their Application in Scintillation Counting.  

NASA Astrophysics Data System (ADS)

Available from UMI in association with The British Library. Requires signed TDF. Several complexes of lithium derived from 1,2 -naphthoquinone 1-oxime and 1,2-naphthoquinone 2-oxime have been prepared and characterised using analytical, spectroscopic and thermal gravimetric techniques. I.r. studies indicate that the ligands in these complexes are essentially quinoneoximic in character. For the complex Li(1-nqo)(1-nqoH) cdotEtOH the quinoneoximic character has been confirmed by X-ray crystallography. All the lithium complexes were found to be stable towards atmospheric oxygen and water. Their reactivity towards dimethylacetylene dicarboxylate was investigated and compared to that of the copper quinoneoximato complexes. Each of the lithium complexes reacted readily with the acetylene dicarboxylate to give a novel nucleophilic addition product isomeric to the Diels-Alder adduct (1,4-oxazine) obtained from the copper complexes. Re-examination of the behaviour of the copper quinoneoximato complexes towards dimethylacetylene dicarboxylate has given an insight to the mechanism of the reaction and has shown that the copper complexes also act as catalysts in the conversion of 1,4-oxazine derivatives to 1,3-oxazoles. Several lithium carboxylato and dithiocarbamato complexes have been prepared. For the dithiocarbamato complexes a new synthetic method involving the reaction of carbon disulphide and the amine with lithium chloride was developed during this study. Solubility studies were carried out on several complexes of types Li(RCO_2), Li(R _2NCS_2)(R _2NCSSH), Li(nqo) and M(qo) _{rm n} (M = Li, Na ^2, K, Ni, Co) in polar and non-polar solvents. Maximum solubility was observed in pyridine, dimethylsulphoxide and ethanol. The scintillation efficiency of pyridine, dimethylsulphoxide and ethanol was examined in commercially available scintillator mixtures and in scintillator mixtures developed during this study. The scintillation efficiency of the lithium complexes derived from the mono-oximes of 1,2-naphthoquinone, carboxylic and dithiocarbamic acids was also investigated. The latter two set of complexes proved promising for loading liquid scintillation counters, when present as 'solid' in the scintillator mixture.

Gaganatsou, Paraskevi

1987-09-01

251

Pulsed microwave irradiation effects on the dynamic behavior of a photochemically generated radical pair in a micellar solution  

NASA Astrophysics Data System (ADS)

The radical pair dynamics in a photochemical hydrogen abstraction reaction of 2-methyl-1,4-naphthoquinone in a sodium dodecylsulfate micelle was modulated by a microwave pulse. After a short resonant 180° microwave pulse, the recombination of the radical pair was enhanced, its rate constant being determined to be (8.3±0.8)×10 6 s -1. Other kinetic parameters were determined by the scanning of the microwave pulse position as follows: the formation of the radical pair (3.3±0.3)×10 7 s -1, the relaxation rate from the triplet (T ±1) levels to the singlet-triplet (T 0) mixed one (3.3±0.3)×10 5 s -1 at 331 mT, and the radical escape rate (5.8±0.6)×10 5 s -1.

Sakaguchi, Yoshio; Astashkin, Andrei V.; Tadjikov, Boris M.

1997-12-01

252

Synthesis of 3-[(N-Carboalkoxy)ethylamino]-indazole-dione Derivatives and Their Biological Activities on Human Liver Carbonyl Reductase  

PubMed Central

A series of indazole-dione derivatives were synthesized by the 1,3-dipolar cycloaddition reaction of appropriate substituted benzoquinones or naphthoquinones and N-carboalkoxyamino diazopropane derivatives. These compounds were evaluated for their effects on human carbonyl reductase. Several of the analogs were found to serve as substrates for carbonyl reductase with a wide range of catalytic efficiencies, while four analogs display inhibitory activities with IC50 values ranging from 3 – 5 ?M. Two of the inhibitors were studied in greater detail and were found to be noncompetitive inhibitors against both NADPH and menadione with KI values ranging between 2 and 11 ?M. Computational studies suggest that conformation of the compounds may determine whether the indazole-diones bind productively to yield product or nonproductively to inhibit the enzyme.

Berhe, Solomon; Slupe, Andrew; Luster, Choice; Charlier, Henry A.; Warner, Don L.; Zalkow, Leon H.; Burgess, Edward M.; Enwerem, Nkechi M.; Bakare, Oladapo

2009-01-01

253

Comparison of the antiinflammatory effects of Drosera rotundifolia and Drosera madagascariensis in the HET-CAM assay.  

PubMed

The antiinflammatory effects of ethanol and aqueous extracts from Drosera rotundifolia and from Drosera madagascariensis were compared in vivo in the HET-CAM assay. Both extracts from D. rotundifolia and the ethanol extract from D. madagascariensis showed remarkable efficacy at doses of 500 microg/pellet. The inhibition of the inflammation by the extracts was stronger than that by 50 microg hydrocortisone/pellet. In contrast, there was only a very weak effect observed at a dose of 500 microg/pellet of the water extract from D. madagascariensis. The chemical analyses of the extracts showed that the effect cannot be attributed to naphthoquinones, but might be due to flavonoids. Ellagic acid obviously plays an important role in the antiangiogenic effect of the Drosera extracts. PMID:16041727

Paper, Dietrich H; Karall, Elisabeth; Kremser, Michaela; Krenn, Liselotte

2005-04-01

254

Secondary metabolites in in vitro cultured plants of the genus Drosera.  

PubMed

Extracts from plantlets of different species of the genus Drosera, grown as in vitro cultures, were evaluated for the level of phenolic secondary metabolites from the group of naphthoquinones and flavonols. The profiles of natural products in the extracts obtained from different species were monitored by HPLC with UV detection at 260 and 330 nm. On the basis of the data obtained, Drosera binata, the species with the highest amount of plumbagin, was selected for further studies. The most effective method of extraction of quinones was established and the composition of phenolic secondary metabolites in the tissues was determined. For the identification of phenolic compounds, HPLC-UV and HPLC-ESI/MS were applied. PMID:15997845

Marczak, L; Kawiak, A; Lojkowska, E; Stobiecki, M

2005-01-01

255

Heptaketides from Corynespora sp. inhabiting the cavern beard lichen, Usnea cavernosa: first report of metabolites of an endolichenic fungus.  

PubMed

Two new heptaketides, corynesporol (1) and 1-hydroxydehydroherbarin (2), along with herbarin (3) were isolated from an endolichenic fungal strain, Corynespora sp. BA-10763, occurring in the cavern beard lichen Usnea cavernosa. The structures of 1-3 were elucidated from their spectroscopic data. Aerial oxidation of corynesporol (1) yielded herbarin (3). Acetylation of 1 afforded the naphthalene derivative 4, whereas acetylation of 3 gave the corresponding naphthoquinone 6 and dehydroherbarin (5). All compounds were evaluated for their cytotoxicity and ability to inhibit migration of human metastatic breast and prostate cancer cell lines MDA-MB-231 and PC-3M, respectively. Dehydroherbarin (5) inhibited migration of both cell lines at concentrations not toxic to these cell lines. This is the first report of metabolites from an endolichenic fungus. PMID:17988097

Paranagama, Priyani A; Wijeratne, E M Kithsiri; Burns, Anna M; Marron, Marilyn T; Gunatilaka, Malkanthi K; Arnold, A Elizabeth; Gunatilaka, A A Leslie

2007-11-01

256

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

257

Antioxidant and immunomodulatory constituents of henna leaves.  

PubMed

The immunomodulatory bioassay-guided fractionation of the methanolic extract of henna (Lawsonia inermis L.; syn. Lawsonia alba L.) leaves resulted in the isolation of seven compounds; three have been isolated for the first time from the genus, namely p-coumaric acid, 2-methoxy-3-methyl-1,4-naphthoquinone and apiin, along with the previously isolated compounds: lawsone, apigenin, luteolin, and cosmosiin. Structural elucidation of the isolated compounds was based upon their physical, chemical as well as spectroscopic characters. Their immuomodulatory profile was studied using an in vitro immunoassay, the lymphocyte transformation assay. The ABTS [2,2'-azino-bis (3-ethyl benzthiazoline-6-sulfonic acid)], free radical scavenging assay depicted that all isolated compounds exhibited antioxidant activity comparable to that of ascorbic acid. PMID:15813363

Mikhaeil, Botros R; Badria, Farid A; Maatooq, Galal T; Amer, Mohamed M A

2004-01-01

258

Synthesis and cytotoxic activities of some 2-Arylnaphtho [2,3-d]oxazole-4,9-dione derivatives on androgen-dependent (LNCaP) and androgen-independent (PC3) human prostate cancer cell lines  

PubMed Central

Summary The synthesis of five 2-arylnaphtho[2,3-d]oxazole- 4,9-dione derivatives was accomplished by refluxing 2-amino-3-bromo-1,4-naphthoquinone with appropriate benzoyl chloride analogs at elevated temperatures. In vitro anticancer evaluation of these compounds was performed on androgen-dependent, LNCaP, and androgen-independent, PC3, human prostate cancer cell lines. In general, these compounds displayed slightly stronger cytotoxicity on the androgen-dependent LNCaP than on the androgen-independent PC3 prostate cancer cell lines. The meta-substituted 2-(3-Chloro-phenyl)-naphtho[2,3-d]oxazole-4,9- dione (10) appear to display the best cytotoxicity on both cell lines with an IC50 of 0.03 ?M on LNCaP and 0.08 ?M on PC3 after 5 days of exposure.

Brandy, Yakini; Ononiwu, Innocent; Adedeji, Dolapo; Williams, Vonetta; Mouamba, Claudia; Kanaan, Yasmine; Copeland, Robert L.; Wright, Dwayne A.; Butcher, Ray J.; Denmeade, Samuel R.

2013-01-01

259

Synthesis and cytotoxic activities of some 2-arylnaphtho[2,3-d]oxazole-4,9-dione derivatives on androgen-dependent (LNCaP) and androgen-independent (PC3) human prostate cancer cell lines.  

PubMed

The synthesis of five 2-arylnaphtho[2,3-d]oxazole-4,9-dione derivatives was accomplished by refluxing 2-amino-3-bromo-1,4-naphthoquinone with appropriate benzoyl chloride analogs at elevated temperatures. In vitro anticancer evaluation of these compounds was performed on androgen-dependent, LNCaP, and androgen-independent, PC3, human prostate cancer cell lines. In general, these compounds displayed slightly stronger cytotoxicity on the androgen-dependent LNCaP than on the androgen-independent PC3 prostate cancer cell lines. The meta-substituted 2-(3-Chloro-phenyl)-naphtho[2,3-d]oxazole-4,9-dione (10) appear to display the best cytotoxicity on both cell lines with an IC(50) of 0.03 ?M on LNCaP and 0.08 ?M on PC3 after 5 days of exposure. PMID:21243402

Brandy, Yakini; Ononiwu, Innocent; Adedeji, Dolapo; Williams, Vonetta; Mouamba, Claudia; Kanaan, Yasmine; Copeland, Robert L; Wright, Dwayne A; Butcher, Ray J; Denmeade, Samuel R; Bakare, Oladapo

2012-08-01

260

Modulation of intracellular iron levels by oxidative stress implicates a novel role for iron in signal transduction  

PubMed Central

Reactive oxygen species (ROS) display cytotoxicity that can be exacerbated by iron. Paradoxically, HeLa cells treated with the ROS-generators menadione and 2,3-dimethoxy-1,4-naphthoquinone display increased free labile iron. HeLa cells exposed to ROS undergo apoptosis but iron chelation limits the extent of cell death suggesting the rise in intracellular iron plays a signaling role in this pathway. This idea is supported by the fact that iron chelation also alters the pattern of ROS-induced phosphorylation of stress-activated protein kinases SAPK/JNK and p38 MAPK. Thus, ROS-induced increases in cellular free iron contribute to signaling events triggered during oxidative stress response.

Deb, Suman; Johnson, Erin E.; Robalinho-Teixeira, Raquel L.

2010-01-01

261

Photoinduced spin-polarized radical ion pair formation in a fixed-distance photosynthetic model system at 5 K  

SciTech Connect

Photoinduced, multistep charge separation in bacterial reaction centers proceeds from the lowest excited singlet state of the dimeric bacteriochlorophyll electron donor in two steps, to yield a weakly interacting dimer cation-quinone anion radical pair, P{sup +}-Q{sup {minus}}, separated by 28 {angstrom}. Recently, we developed criteria for achieving high quantum yield charge separation in porphyrin-based-donor-acceptor systems at cryogenic temperatures. Using this information as a predictive model, we synthesized compound 1, TAPD-ZP-NQ, which consists of a zinc porphyrin primary electron donor, ZP, positioned between a naphthoquinone electron acceptor, NQ, and an N,N,N,N-tetraalkyl-p-phenylenediamine secondary electron donor, TADP.

Wasielewski, M.R.; Gaines, G.L. III; O'Neil, M.P.; Svec, W.A.; Niemczyk, M.P. (Argonne National Laboratory, IL (USA))

1990-05-23

262

Pharmacological properties of shikonin - a review of literature since 2002.  

PubMed

The naphthoquinone shikonin is the main active principle of Zicao, a traditional Chinese herbal medicine made from the dried root of Lithospermum erythrorhizon. Studies carried out over the past 30 years have provided a scientific basis for the use of Zicao which has been long employed in folk medicine to treat a variety of inflammatory and infectious diseases. In particular, shikonin has been shown to possess many diverse properties, including antioxidant, anti-inflammatory, antithrombotic, antimicrobial, and wound healing effects. The fact that shikonin shows so many beneficial properties has increased the interest in this molecule dramatically, especially in the past few years. The aim of this review is to provide an update of the new data published on shikonin, whose wide spectrum of pharmacological effects as well as pharmacokinetic properties and toxicity make it a highly interesting target molecule. PMID:24155261

Andújar, Isabel; Ríos, José Luis; Giner, Rosa María; Recio, María Carmen

2013-12-01

263

Onosma L.: A review of phytochemistry and ethnopharmacology  

PubMed Central

The genus Onosma L. (Boraginaceae) includes about 150 species distributed world-wide in which only about 75 plants has been described for its morphology and less than 10 plants for their chemical constituents and clinical potential. The phytochemical reports of this genus revels that it comprise mainly aliphatic ketones, lipids, naphthazarins, alkaloids, phenolic compounds, naphthoquinones, flavones while most important are shikonins and onosmins. The plants are traditionally used as laxative, anthelmintic and for alexipharmic effects. The plants are also equally use in eye, blood diseases, bronchitis, abdominal pain, stangury, thirst, itch, lecoderma, fever, wounds, burns, piles and urinary calculi. The flowers of various plants are prescribed as stimulants, cardiotonic, in body swelling while leaves are used as purgative and in cutaneous eruptions. The roots are used for coloring food stuffs, oils and dying wool and in medicinal preparations. This review emphasizes the distribution, morphology, phytochemical constituents, ethnopharmacology, which may help in future research.

Kumar, Neeraj; Kumar, Rajnish; Kishore, Kamal

2013-01-01

264

Lithospermum erythrorhizon suppresses high-fat diet-induced obesity, and acetylshikonin, a main compound of Lithospermum erythrorhizon, inhibits adipocyte differentiation.  

PubMed

Lithospermum erythrorhizon, which has traditionally been used as a vegetable and to make the liquor Jindo Hongju, contains several naphthoquinone pigments, including shikonin. This study aimed to evaluate the antiobesity effects of Lithospermum erythrorhizon ethanol extract (LE) and elucidate the underlying mechanism. C57BL/6J mice were fed a normal or high-fat diet with or without LE supplementation for 8 weeks. LE reduced high-fat diet-induced increases in body weight, white adipose tissue mass, serum triglyceride and total cholesterol levels, and hepatic lipid levels while decreasing lipogenic and adipogenic gene expression. Furthermore, acetylshikonin suppressed adipocyte differentiation in a dose-dependent manner and significantly attenuated adipogenic transcription factor expression in 3T3-L1 cells. These findings suggest that Lithospermum erythrorhizon prevents obesity by inhibiting adipogenesis through downregulation of genes involved in the adipogenesis pathway and may be a useful dietary supplement for the prevention of obesity. PMID:22900585

Gwon, So Young; Ahn, Ji Yun; Chung, Chang Hwa; Moon, BoKyung; Ha, Tae Youl

2012-09-12

265

Shikonin blocks migration and invasion of human breast cancer cells through inhibition of matrix metalloproteinase-9 activation.  

PubMed

Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, has been reported to promote tumor cell death. However, there are few reports concerning its effect on metastasis-related cell invasion and migration behavior. In the present study, we investigated the effect of shikonin on human breast cancer invasion and migration. We found that shikonin inhibited phorbol 12-myristate 13-acetate (PMA)-induced cell migration and invasion in MCF-7 breast cancer cells, which was correlated with modulation of matrix metalloproteinase-9 (MMP-9) through suppression of both expression and proteolytic and promoter activity. We also found that shikonin inhibited both MMP-9 expression and promoter activity in MDA-MB?231 cells with high metastatic potential. These results indicated that shikonin induces the suppression of migration and invasion through modulation of MMP-9 in human breast cancer cells. Therefore, shikonin may be a potential anticancer drug for human breast cancer therapy. PMID:24789371

Jang, Soon Young; Lee, Jae Koan; Jang, Eun Hyang; Jeong, Seo Young; Kim, Jong-Ho

2014-06-01

266

Larvicidal activity of extracts from three Plumbago spp against Anopheles gambiae.  

PubMed

Three Plumbago spp have been tested for mosquito larvicidal activity. The crude extracts exhibiting the highest larvicidal activity against Anopheles gambiae were hexane (LC50 = 6.4 microg/mL) and chloroform (LC50 = 6.7 microg/mL) extracts from Plumbago zeylanica Linn, chloroform (LC50 = 6.7 ug/mL) extract from Plumbago stenophylla Bull and ethyl acetate (LC50 = 4.1 microg/mL) extract from Plumbago dawei Rolfe. These LC50 values were within 95% confidence limits. 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin) 1 (LC50 = 1.9 microg/mL) and beta-sitosterol 2 were characterised from ethyl acetate extract of root bark of P. dawei, a native medicinal plant growing in Kenya, based on spectral analysis and comparisons with data in literature. PMID:19876552

Maniafu, Barasa M; Wilber, Lwande; Ndiege, Isaiah O; Wanjala, Cornelius C; Akenga, Teresa Ayuko

2009-09-01

267

Solubilities of p-quinone and 9,10-anthraquinone in supercritical carbon dioxide  

SciTech Connect

Equilibrium solubilities of p-quinone (1,4-benzoquinone) and 9,10-anthraquinone at 35 C and 45 C in supercritical carbon dioxide over a pressure range of about (85--300) bar have been measured using a supercritical fluid extractor coupled with a high-pressure liquid chromatography apparatus. The solubility results, along with those reported in the literature for 1,4-naphthoquinone, are correlated with a modified Peng-Robinson equation of state. The ability of a supercritical fluid to separate a multicomponent mixture is unique, since it utilizes the salient features of both distillation and liquid extraction. The solubility of a solute in a supercritical fluid is the most important thermophysical property that has to be determined and modeled for an efficient design of any extraction based on supercritical solvents.

Coutsikos, P.; Magoulas, K.; Tassios, D. [National Technical Univ. of Athens (Greece)] [National Technical Univ. of Athens (Greece)

1997-05-01

268

A new dilactone from the seeds of Gaultheria yunnanensis.  

PubMed

Gaultheriadiolide (1), a new compound, together with the known dauosterol (2), ginkgetin (3), myricetin (4), 6-ethyl-5-hydroxy-2,7-dimethoxy-1,4-naphthoquinone (5), ursolic acid (6), methyl salicylate 2-O-beta-D-xylosyl(1-->6)beta-D-glucopyranoside (7), and methyl salicylate 2-O-beta-D-glucopyranoside (8) were isolated from Gaultheria yunnanensis. The structure was elucidated on the basic of spectral analysis, especially 1D and 2D NMR. Primary bioassays showed that compound 1 had medium cytotoxic activity against HEp-2 and HepG2 Cells, with IC(50) of 23.337 microM and 29.4497 microM, respectively. PMID:19628028

Li, Jun; Li, Fu; Lu, Yuan-Yuan; Su, Xiao-Jian; Huang, Cui-Ping; Lu, Xue-Wen

2010-01-01

269

Acute lethal toxicity of environmental pollutants to aquatic organisms.  

PubMed

The acute lethal toxicity of environment pollutants including chlorophenol, haloalkane, quinone, and substituted nitrobenzene (i.e., nitrophenol, nitrobenzene, nitrotoluene, and aniline) compounds to aquatic organisms was determined. Determination of toxicity of chemicals was performed with chlorella, daphnia, carp, and tilapia. The toxicity of chlorophenols had no relation to the number of chlorine atoms on the benzene ring, but monochlorophenol had lower activity than more chlorine-substituted compounds. The tolerance levels of daphnia and carp to haloalkanes was found to be higher than that of chlorella; toxicity to chlorella was several hundred times higher than to daphnia. The toxicity of naphthoquinone compounds to chlorella and carp was higher than that of anthraquinone. A compound with a monochloride substitution on anthraquinone ring was less toxic to carp than those substituted with amine, hydroxyl, and dichlorine groups. Nitrobenzene compounds with an additional substitution group on the p position were extremely toxic to daphnia and carp. PMID:12061826

Yen, Jui-Hung; Lin, Kuo-Hsiung; Wang, Yei-Shung

2002-06-01

270

One-pot, sequential four-component synthesis of benzo[c]pyrano[3,2-a]phenazine, bis-benzo[c]pyrano[3,2-a]phenazine and oxospiro benzo[c]pyrano[3,2-a]phenazine derivatives using 1,4-diazabicyclo[2.2.2]octane (DABCO) as an efficient and reusable solid base catalyst.  

PubMed

1,4-Diazabicyclo[2.2.2]octane (DABCO) has been used as an efficient and reusable solid base catalyst for the one-pot, two-step, four-component synthesis of pyrano[3,2-a]phenazine derivatives by the condensation reaction of 2-hydroxy-1,4-naphthoquinone, 1,2-diamines, carbonyl compounds and alkylmalonates under conventional heating as well as microwave irradiation. This procedure has also been applied successfully for the synthesis of novel bis- benzo[c]pyrano[3,2-a]phenazine and oxospiro benzo[c]pyrano[3,2-a]phenazine derivatives. Using this procedure, all the products were obtained in good to excellent yields. The catalyst has been recovered and reused several times without any loss of reactivity. PMID:23665995

Hasaninejad, Alireza; Firoozi, Somayeh

2013-08-01

271

Structural modification study of bis(substituted aminoalkylamino)anthraquinones. An evaluation of the relationship of the [2-[(2-hydroxyethyl)amino]ethyl]amino side chain with antineoplastic activity.  

PubMed

Several anthraquinones containing the [2-[(2-hydroxyethyl)amino]ethyl]amino, the [2-(dimethylamino)ethyl]amino, and the 2-(dimethylamino)ethoxy groups were prepared. Preparation of a lucanthone analogue, a 7-chloroquinoline derivative, and derivatives of naphthoquinones containing the [2-[(2-hydroxyethyl)amino]ethyl]amino side chain and related amino-substituted side chains was also conducted. It was found that the antineoplastic activity of anthraquinones containing the [2-[(2-hydroxyethyl)amino]ethyl]amino side chain is superior to those containing the tertiary amino side chain. However, the presence of the [2-[(2-hydroxyethyl)amino]ethyl]amino chain is an important, but not a sufficient, factor for good antineoplastic activity, as indicated by the lack of significant biological activity of other ring systems containing this side chain. PMID:458801

Zee-Cheng, R K; Podrebarac, E G; Menon, C S; Cheng, C C

1979-05-01

272

Derivatization strategies for the determination of biogenic amines in wines by chromatographic and electrophoretic techniques.  

PubMed

This paper revises the derivatization approaches for the determination of biogenic amines in wines. Since most of these amines display poor spectroscopic features to be detected by UV absorption or emission (fluorescence) spectroscopy, derivatization is necessary to attain the desired sensitivity. Reagents such as o-phthaldialdehyde, fluorenylmethylchloroformate, dansyl-Cl and dabsyl-Cl have widely been used for analytical labeling through amino group. A comparison of features of off- and on-line pre- and post chromatographic/electrophoretic labeling is given using 1,2-naphthoquinone-4-sulfonate (NQS) as an example. The evaluation of the influence of the wine sample composition on the derivatization process indicates that pre-column labeling may undergo more severe matrix effects. PMID:21185242

Hernández-Cassou, Santiago; Saurina, Javier

2011-05-15

273

Antibacterial activity of plumbagin derivative-rich Plumbago indica root extracts and chemical stability.  

PubMed

The extraction studies and a one-step purification of the crude extract of Plumbago indica using silica-gel vacuum chromatography provided a plumbagin derivative-rich P. indica root extract (PPE). The PPE was standardised to contain total plumbagin derivatives not less than 13% w/w. Antibacterial activities of the standardised PPE and three naphthoquinones, plumbagin, elliptinone and 3,3'-biplumbagin, against Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis were evaluated by using the microdilution assay. The bactericidal activities of the PPE against these bacteria were much stronger than those of elliptinone and 3,3'-biplumbagin and almost equal to those of plumbagin. Stability of the PPE was determined under various conditions through a period of four months. The PPE was stable over a period of four months when stored as a dried powder but only in a well-closed container protected from light under 4 ± 2°C. PMID:24483166

Kaewbumrung, Sermwut; Panichayupakaranant, Pharkphoom

2014-01-01

274

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

275

[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

276

Lapachol induces clastogenic effects in rats.  

PubMed

Lapachol is a naturally occurring naphthoquinone derivative found in the heartwood of several plants, particularly those of the genus Tabebuia (Bignoneaceae). Despite its use as a therapeutic product with anti-inflammatory, analgesic, antipsoriatic, trypanocidal effects, among others, its in vivo mutagenic potential has still not been investigated. This paper reports the effects after a single oral administration of lapachol in the in vivo micronucleus (MN) and chromosome aberration (CA) assays. Both assays were performed using bone marrow cells from male Wistar rats. The animals were treated by oral gavage with hydroalcoholic solutions of lapachol at the doses of 122, 244 and 365 mg/kg, chosen on the basis of the LD(50) in male rats. The results show that the higher administered lapachol dose induced a significant increase in the frequency of micronucleated polychromatic erythrocytes (MNPCE) and CAs in rat bone marrow cells, indicating that lapachol shows clastogenic effects under the experimental conditions used. PMID:20112181

Maistro, Edson Luis; Fernandes, Diego Mota; Pereira, Fernanda Maria; Andrade, Sergio Faloni

2010-06-01

277

Reproductive toxicity of lapachol in adult male Wistar rats submitted to short-term treatment.  

PubMed

Lapachol is a therapeutic naphthoquinone, but little is known about its general and reproductive toxicity. In female rats, a high incidence of resorptions and fetal mortality has been reported. This work analyses the effect of the short-term administration of lapachol on vital and reproductive organs, and sperm production in Wistar rats. Adult animals were treated with 1 mL of lapachol hydroalcohol solution (100 mg/kg of body weight) for 5 days and killed 3 (T1) and 14 days (T2) after the end of treatment. Body and organ weights and sperm production were evaluated. The administration of lapachol significantly reduced the weight of the seminal vesicle (T1 animals). No significant alteration of gamete production, body weight and the weight of the other organs analysed were detected. The results suggest a reproductive toxicity effect of lapachol, indicating the seminal vesicle as a possible target organ. PMID:17421057

de Cássia da Silveira E Sá, Rita; de Oliveira Guerra, Martha

2007-07-01

278

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

279

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

PubMed

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), 4-hydroxylonchocarpin (flavonoid) and MAB3 (coumarin) increased significantly against all studied MDR bacteria. Laurentixanthone B, 4-hydroxylonchocarpin and MAB3 contained the same pharmacophoric moiety as plumbagin. This study indicates that the AcrAB-TolC (Enterobacteriaceae) and MexAB-OprM (Pseudomonas aeruginosa) efflux pumps are involved in resistance of Gram-negative bacteria to most of the natural products. PMID:21163632

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

2011-02-01

280

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

281

Effects of Atovaquone and Diospyrin-Based Drugs on the Cellular ATP of Pneumocystis carinii f. sp. carinii  

PubMed Central

Atovaquone (also called Mepron, or 566C80) is a napthoquinone used for the treatment of infections caused by pathogens such as Plasmodium spp. and Pneumocystis carinii. The mechanism of action against the malarial parasite is the inhibition of dihydroorotate dehydrogenase (DHOD), a consequence of blocking electron transport by the drug. As an analog of ubiquinone (coenzyme Q [CoQ]), atovaquone irreversibly binds to the mitochondrial cytochrome bc1 complex; thus, electrons are not able to pass from dehydrogenase enzymes via CoQ to cytochrome c. Since DHOD is a critical enzyme in pyrimidine biosynthesis, and because the parasite cannot scavenge host pyrimidines, the drug is lethal to the organism. Oxygen consumption in P. carinii is inhibited by the drug; thus, electron transport has also been identified as the drug target in P. carinii. However, unlike Plasmodium DHOD, P. carinii DHOD is inhibited only at high atovaquone concentrations, suggesting that the organism may salvage host pyrimidines and that atovaquone exerts its primary effects on ATP biosynthesis. In the present study, the effect of atovaquone on ATP levels in P. carinii was measured directly from 1 to 6 h and then after 24, 48, and 72 h of exposure. The average 50% inhibitory concentration after 24 to 72 h of exposure was 1.5 ?g/ml (4.2 ?M). The kinetics of ATP depletion were in contrast to those of another family of naphthoquinone compounds, diospyrin and two of its derivatives. Whereas atovaquone reduced ATP levels within 1 h of exposure, the diospyrins required at least 48 h. After 72 h, the diospyrins were able to decrease ATP levels of P. carinii at nanomolar concentrations. These data indicate that although naphthoquinones inhibit the electron transport chain, the molecular targets in a given organism are likely to be distinct among members of this class of compounds.

Cushion, Melanie T.; Collins, Margaret; Hazra, Banasri; Kaneshiro, Edna S.

2000-01-01

282

MOF with hydroxynaphthoquinone as organic linker: Molecular structure of [Zn(Chlorolawsone)2(H2O)2] and thermogravimetric studies  

NASA Astrophysics Data System (ADS)

Zinc complexes as MOF with hydroxynaphthoquinone as organic linkers are synthesized and characterized. The complexes Zn-1; [Zn(lawsone)2(H2O)2]?3H2O and Zn-2; [Zn(chlorolawsone)2(H2O)2]?H2O, where lawsone is 2-hydroxy-1,4-naphthoquinone and chlorolawsone is 3-chloro-2-hydroxy-1,4-naphthoquinone, serve as hosts for adsorbed water molecules. ?Cdbnd O shows shift towards lower frequencies ˜25 cm-1 in Zn-1 and ˜35 cm-1 in Zn-2 in FTIR spectra. 1H NMR shows upfield shift in Zn-1 and downfield shift in Zn-2 to the benzenoid ring protons. Bathochromic shift has been observed to the charge transfer band in UV-visible spectra of both complexes. The mass loss of adsorbed water molecules have been observed <100 °C in thermogravimetric (TG) studies. Three adsorbed water molecules are present in Zn-1, while one in Zn-2. X-ray diffraction studies of Zn-2 show, distorted octahedral geometry around Zn(II). The two chlorolawsone ligands are in plane with the metal, while water molecules are trans to this plane. Formation of MOF has been observed in the synthesis of Zn-2 with chlorolawsone as organic linkers. The structure is stabilized by Osbnd H⋯O, Csbnd H⋯O hydrogen bonding H-bonding along with Cl⋯? interactions to form a beautiful MOF architecture. Zn(II) atoms along with organic ligand form a tetramer via Osbnd H?O interactions. The shortest Zn⋯Zn distance is 5.04 Å.

Salunke-Gawali, Sunita; Kathawate, Laxmi; Puranik, Vedavati G.

2012-08-01

283

Effect of venotropic drugs on the respiratory activity of isolated mitochondria and in endothelial cells.  

PubMed

Several drugs used in the treatment of chronic peripheral ischaemic and venous diseases, i.e. aescine, Cyclo 3, Ginkor Fort, hydroxyethylrutosides, naftidrofuryl, naphthoquinone and procyanidolic oligomers, were tested on the mitochondrial respiratory activity. The results show that all these drugs protected human endothelial cells against the hypoxia-induced decrease in ATP content. In addition, they all induced a concentration-dependent increase in respiratory control ratio (RCR) of liver mitochondria pre-incubated with the drugs for 60 min. The drugs were divided into two groups according to their effects. The first group (A), comprising aescine, Ginkor Fort, naftidrofuryl and naphthoquinone, increased RCR by decreasing state 4 respiration rate. The second group of drugs (B), comprising hydroxyethylrutosides, procyanidolic oligomers and Cyclo 3, increased RCR by increasing state 3 respiration rate. The drugs of group A were able to prevent the inhibition of complexes I and III respectively by amytal and antimycin A while the first two drugs of group B increased adenine nucleotide translocase activity. Cyclo 3 inhibited the carbonylcyanide m-chlorophenyl hydrazone (mCCP)-induced uncoupling of mitochondrial respiration. None of these seven drugs could protect complexes IV and V, respectively, from inhibition by cyanide and oligomycin. When tested on endothelial cells the drugs of group A, in contrast to group B, prevented the decrease in ATP content induced by amytal or antimycin A. The present results suggest that the protective effects on mitochondrial respiration activity by these venotropic drugs may explain their protective effect on the cellular ATP content in ischaemic conditions and some of their beneficial therapeutic effect in chronic vascular diseases. PMID:10928952

Janssens, D; Delaive, E; Houbion, A; Eliaers, F; Remacle, J; Michiels, C

2000-08-01

284

Effect of venotropic drugs on the respiratory activity of isolated mitochondria and in endothelial cells  

PubMed Central

Several drugs used in the treatment of chronic peripheral ischaemic and venous diseases, i.e. aescine, Cyclo 3, Ginkor Fort, hydroxyethylrutosides, naftidrofuryl, naphthoquinone and procyanidolic oligomers, were tested on the mitochondrial respiratory activity. The results show that all these drugs protected human endothelial cells against the hypoxia-induced decrease in ATP content. In addition, they all induced a concentration-dependent increase in respiratory control ratio (RCR) of liver mitochondria pre-incubated with the drugs for 60?min. The drugs were divided into two groups according to their effects. The first group (A), comprising aescine, Ginkor Fort, naftidrofuryl and naphthoquinone, increased RCR by decreasing state 4 respiration rate. The second group of drugs (B), comprising hydroxyethylrutosides, procyanidolic oligomers and Cyclo 3, increased RCR by increasing state 3 respiration rate. The drugs of group A were able to prevent the inhibition of complexes I and III respectively by amytal and antimycin A while the first two drugs of group B increased adenine nucleotide translocase activity. Cyclo 3 inhibited the carbonylcyanide m-chlorophenyl hydrazone (mCCP)-induced uncoupling of mitochondrial respiration. None of these seven drugs could protect complexes IV and V, respectively, from inhibition by cyanide and oligomycin. When tested on endothelial cells the drugs of group A, in contrast to group B, prevented the decrease in ATP content induced by amytal or antimycin A. The present results suggest that the protective effects on mitochondrial respiration activity by these venotropic drugs may explain their protective effect on the cellular ATP content in ischaemic conditions and some of their beneficial therapeutic effect in chronic vascular diseases.

Janssens, Dominique; Delaive, Edouard; Houbion, Andree; Eliaers, Francois; Remacle, Jose; Michiels, Carine

2000-01-01

285

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

286

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

287

Expression, purification, and characterization of anti-plumbagin single-chain variable fragment antibody in Sf9 insect cell.  

PubMed

Plumbagin (PL; 5-hydroxy-2-methyl-1, 4-naphthoquinone) is an important secondary metabolite, mainly produced in the Plumbago zeylanica L. (Plumbaginaceae). A single-chain variable fragment (scFv) antibody, fusion of the variable regions of the heavy chain and light chain of immunoglobulin against PL (PL-scFv) was expressed by Bac-to-Bac Baculovirus Expression System using Spodoptera frugiperda (Sf9) insect cells and characterized to investigate potential use of PL-scFv as a tool for plant immunomodulation. Functional PL-scFv expressed in the Sf9 insect cells were purified using cation exchange chromatography followed by immobilized metal ion affinity chromatography (IMAC). The yields of the purified PL-scFv in the culture supernatant and Sf9 insect cells were 2.0 mg and 5.2 mg per 1 liter of Sf9 culture medium, respectively. Recombinant purified PL-scFv was then characterized by the indirect competitive enzyme-linked immunosorbent assay (ELISA). The cross-reactivity and sensitivity of PL-scFv expressed in Sf9 insect cells were compared with PL-scFv expressed in Escherichia coli and its parental anti-plumbagin monoclonal antibody (MAb 3A3) secreted from hybridoma cells. Intriguingly, the specificity of the PL-scFv expressed in Sf9 insect cells was found to be different from that expressed in E. coli and parental MAb 3A3, although the detectable level (0.2-25 ?g/mL) was the same in ELISA using each antibody. Even more interestingly, the characteristics of PL-scFv, which have wide cross-reactivity against 1,4-napththoquinone, suggest its potential use as a tool for plant immunomodulation not only for breeding Plumbaginacea family containing PL but also for breeding other medicinal plants containing bioactive naphthoquinones. PMID:21087101

Sakamoto, Seiichi; Taura, Futoshi; Tsuchihashi, Ryota; Putalun, Waraporn; Kinjo, Junei; Tanaka, Hiroyuki; Morimoto, Satoshi

2010-12-01

288

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

289

Preparations and properties of novel positive photosensitive polyimides  

NASA Astrophysics Data System (ADS)

Polyamic acid esters with phenol moieties (Ph-ES) were synthesized from diamines and dicarboxylic acids bonding to phenol moieties through ester linkage. To synthesize the dicarboxylic acids, 1 mol of BTDA was reacted with 2 mol of m-hydroxybenzyl alcohol in NMP. The resultant dicarboxylic acid are predominantly benzyl esters, not phenyl esters, was condensed with ODA, using DCC as condensing agent. The polyimide precursors Ph-ES was actually soluble in basic aqueous solutions. However, its dissolution rate was too low for binder resins used for resists. To increase the resist dissolution rate, polyamic acid PA, which is assumed to be more soluble in the base developer, was added to Ph-ES. The PA was synthesized from BTDA and ODA. Resists containing Ph-ES (60 wt%), PA (20 wt%) and naphthoquinone diazide (20 wt%) gave 4 micron line and space pattern with 5 micron thickness. There was no pattern deformation, even after the polyamic acid ester was heated at 320 degree(s)C to form the polyimides. The PA content was critical to the high resolution achievement. As the content of the PA to Ph-ES increases, the pattern shape of the resist deteriorated rapidly. At more than 40 wt% PA rate, patterns could not be obtained, because fine patterns peeled off form the silicon wafer substrate during the development. This proved that adjusting dissolution rates in basic aqueous solutions is one of the significant points for realizing fine resist patterns.

Hayase, Rumiko H.; Kihara, Naoko; Oyasato, Naohiko; Matake, S.; Oba, Masayuki

1991-06-01

290

Magnetic field dependence of spin dynamics of radical pairs studied by time-resolved RYDMR  

NASA Astrophysics Data System (ADS)

The photochemical reaction of 2-methyl-1,4-naphthoquinone in sodium dodecyl-sulphate micellar solution was investigated with an optical detection ESR apparatus working at 17.44 GHz (Ku-band). The Ku-band RYDMR spectra are obtained from the transient optical absorption and the stationary absorption of the reaction product, and the shift of the spectral peak compared with the spectra at 331 mT is reproduced well by the difference in g of the component radicals. The microwave pulse length dependence shows the quantum beat originated from the conversion between triplet ±1 states and the mixed state of singlet and triplet 0 states by the microwave field. The decay rate of the radical pair in triplet ±1 at 622 mT was determined to be 7.1 ±1.1 ×10 5 s -1 by changing the irradiation time of a short (20 ns) microwave pulse with reference to the laser excitation. This value is smaller than that at 331 mT, as expected by the relaxation mechanism.

Sakaguchi, Yoshio

291

Absorption spectrometric and thermodynamic study of charge transfer complexes of menadione (Vitamin K 3) with a series of phenols  

NASA Astrophysics Data System (ADS)

The electron donor-acceptor (EDA) interactions between menadione (i.e., 2-methyl-1,4-naphthoquinone, which is also called 'Vitamin K 3') and a series of phenols (viz., phenol, resorcinol and p-quinol) have been studied in CCl 4 medium. In all the cases, charge transfer (CT) bands have been located. The CT transition energies ( h?CT) of the complexes are found to change systematically with change in the number and position of the -OH groups in the aromatic ring of the phenol moiety. From the trends in the h?CT values, the Hückel parameters ( hÖ and kC-Ö) for the -OH group have been obtained. The CT transition energies are well correlated with the ionisation potentials of the phenols. From an analysis of this variation the electron affinity of Vitamin K 3 has been found to be 2.28 eV. The stoichiometry of the complexes in each case has been found to be 1(menadione):2 (phenol). Formation constants of the complexes have been determined at four different temperatures from which the enthalpies and entropies of formation of the complexes have been estimated.

Pal, Purnendu; Bhattacharya, Sumanta; Mukherjee, Asok K.; Mukherjee, Dulal C.

2005-03-01

292

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

293

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

294

Development of a microscale cell culture analog to probe naphthalene toxicity.  

PubMed

Prediction of human response to drugs or chemicals is difficult as a result of the complexity of living organisms. We describe an in vitro model that can realistically and inexpensively study the adsorption, distribution, metabolism, elimination, and potential toxicity (ADMET) of chemicals. A microscale cell culture analog (microCCA) is a physical replica of the physiologically based pharmacokinetics (PBPK) model. Such a microfabricated device consists of a fluidic network of channels to mimic the circulatory system and chambers containing cultured mammalian cells representing key functions of animal "organ" systems. This paper describes the application of a two-cell system, four-chamber microCCA ("lung"-"liver"-"other tissue"-"fat") device for proof-of-concept study using naphthalene as a model toxicant. Naphthalene is converted into reactive metabolites (i.e., 1,2-naphthalenediol and 1,2-naphthoquinone) in the "liver" compartment, which then circulate to the "lung" depleting glutathione (GSH) in lung cells. Such microfabricated in vitro devices are potential human surrogates for testing chemicals and pharmaceutics for toxicity and efficacy. PMID:14763858

Viravaidya, Kwanchanok; Sin, Aaron; Shuler, Michael L

2004-01-01

295

?-Lapachone activity in synergy with conventional antimicrobials against methicillin resistant Staphylococcus aureus strains.  

PubMed

The aim of this study was to evaluate the antimicrobial activity of lapachol, ?-lapachone, ?-lapachone and six antimicrobials (ampicillin, amoxicillin/clavulanic acid, cefoxitin, gentamicin, ciprofloxacin and meropenem) against twelve strains of Staphylococcus aureus from which resistance phenotypes were previously determined by the disk diffusion method. Five S. aureus strains (LFBM 01, LFBM 26, LFBM 28, LFBM 31 and LFBM 33) showed resistance to all antimicrobial agents tested and were selected for the study of the interaction between ?-lapachone and antimicrobial agents, busing checkerboard method. The criteria used to evaluate the synergistic activity were defined by the Fractional Inhibitory Concentration Index (FICI). Among the naphthoquinones, ?-lapachone was the most effective against S. aureus strains. FICI values ranged from 0.07 to 0.5, suggesting a synergistic interaction against multidrug resistant S. aureus (MRSA) strains. An additive effect was observed with the combination ?-lapachone/ciprofloxacin against the LFBM 33 strain. The combination of ?-lapachone with cefoxitin showed no added benefit against LFBM 31 and LFBM 33 strains. This study demonstrated that, in general, ?-lapachone combined with beta lactams antimicrobials, fluoroquinolones and carbapenems acts synergistically inhibiting MRSA strains. PMID:24035227

Macedo, L; Fernandes, T; Silveira, L; Mesquita, A; Franchitti, A A; Ximenes, E A

2013-12-15

296

Nitrosative and oxidative stress induced heme oxygenase-1 accumulation in rat mesangial cells.  

PubMed

The formation of nitric oxide (NO.) and superoxide (O2-) promotes rat mesangial cell death. Apoptotic death is characterized by DNA fragmentation, caspase-3 activation and concomitant poly(ADPribose) polymerase cleavage, as well as accumulation of the tumor suppressor protein p53. In close association with apoptotic parameters we noticed upregulation of heme oxygenase by the NO donor S-nitrosoglutathione (GSNO) and the redox cycler 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in a time- and concentration-dependent manner. In response to the NO. donor, heme oxygenase-1 expression was more easily obtained than initiation of apoptosis. Radical (NO./O2-) cogeneration abrogated DNA fragmentation, suppressed caspase activation and lowered p53 accumulation, thereby promoting cell survival of mesangial cells. In contrast, heme oxygenase-1 expression remained elevated under conditions of GSNO/DMNQ coadministration. Conclusively, heme oxygenase-1 is a stress marker for both nitrosative and oxidative stress. Accumulation of heme oxygenase-1 is found under conditions of both, apoptotic cell death and cell survival, thereby questioning a specific cytoprotective role of heme oxygenase-1 under conditions of NO. and/or O2- formation in rat mesangial cells. PMID:9544795

Sandau, K; Pfeilschifter, J; Brüne, B

1998-01-19

297

Menaquinone analogs inhibit growth of bacterial pathogens.  

PubMed

Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, and Streptococcus agalactiae at concentrations of 10 to 200 ?g/ml. Coenzyme Q1 reduced the ability of S. aureus to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit S. aureus growth. The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic reactive oxygen species and affect bacterial plasma membranes and biosynthetic machinery to interfere with two-component systems, respiration, and macromolecular synthesis. These compounds represent a novel class of potential topical therapeutic agents. PMID:23959313

Schlievert, Patrick M; Merriman, Joseph A; Salgado-Pabón, Wilmara; Mueller, Elizabeth A; Spaulding, Adam R; Vu, Bao G; Chuang-Smith, Olivia N; Kohler, Petra L; Kirby, John R

2013-11-01

298

Cytotoxic and antibacterial marfuraquinocins from the deep South China Sea-derived Streptomyces niveus SCSIO 3406.  

PubMed

Four new sesquiterpenoid naphthoquinones, marfuraquinocins A-D (1-4), and two new geranylated phenazines, phenaziterpenes A (5) and B (6), were isolated from the fermentation broth of Streptomyces niveus SCSIO 3406, which originated from a South China Sea sediment sample obtained from a depth of 3536 m. The structures of 1-6 were elucidated on the basis of extensive MS and one-dimensional and two-dimensional NMR spectroscopic analyses. In a panel of cytotoxicity and antibacterial assays, 1 and 3 were found to inhibit a NCI-H460 cancer cell line with IC50 values of 3.7 and 4.4 ?M, respectively. Compounds 1, 3, and 4 exhibited antibacterial activities against Staphylococcus aureus ATCC 29213 with equivalent MIC values of 8.0 ?g/mL; compounds 3 and 4 each showed antibacterial activity against methicillin-resistant Staphylococcus epidermidis (MRSE) shhs-E1 with MIC values of 8.0 ?g/mL. PMID:24251399

Song, Yongxiang; Huang, Hongbo; Chen, Yuchan; Ding, Jie; Zhang, Yun; Sun, Aijun; Zhang, Weimin; Ju, Jianhua

2013-12-27

299

Effects of several quinones on insulin aggregation.  

PubMed

Protein misfolding and aggregation are associated with more than twenty diseases, such as neurodegenerative diseases and metabolic diseases. The amyloid oligomers and fibrils may induce cell membrane disruption and lead to cell apoptosis. A great number of studies have focused on discovery of amyloid inhibitors which may prevent or treat amyloidosis diseases. Polyphenols have been extensively studied as a class of amyloid inhibitors, with several polyphenols under clinical trials as anti-neurodegenerative drugs. As oxidative intermediates of natural polyphenols, quinones widely exist in medicinal plants or food. In this study, we used insulin as an amyloid model to test the anti-amyloid effects of four simple quinones and four natural anthraquinone derivatives from rhubarb, a traditional herbal medicine used for treating Alzheimer's disease. Our results demonstrated that all eight quinones show inhibitory effects to different extent on insulin oligomerization, especially for 1,4-benzoquinone and 1,4-naphthoquinone. Significantly attenuated oligomerization, reduced amount of amyloid fibrils and reduced hemolysis levels were found after quinones treatments, indicating quinones may inhibit insulin from forming toxic oligomeric species. The results suggest a potential action of native anthraquinone derivatives in preventing protein misfolding diseases, the quinone skeleton may thus be further explored for designing effective anti-amyloidosis compounds. PMID:25008537

Gong, Hao; He, Zihao; Peng, Anlin; Zhang, Xin; Cheng, Biao; Sun, Yue; Zheng, Ling; Huang, Kun

2014-01-01

300

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

301

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

302

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

303

Spectrophotometric determination of boron based on charge transfer reaction  

NASA Astrophysics Data System (ADS)

Boron determination by a charge transfer spectophotometric 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 + 0.01326 C (?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.

Ma, Linjin; Zhang, Zhenxuan; Li, Quanmin

2011-08-01

304

Induction of apoptosis in HL-60 cells through the ROS-mediated mitochondrial pathway by ramentaceone from Drosera aliciae.  

PubMed

Ramentaceone (1) is a naphthoquinone constituent of Drosera aliciae that exhibits potent cytotoxic activity against various tumor cell lines. However, its molecular mechanism of cell death induction has still not been determined. The present study demonstrates that 1 induces apoptosis in human leukemia HL-60 cells. Typical morphological and biochemical features of apoptosis were observed in 1-treated cells. Compound 1 induced a concentration-dependent increase in the sub-G1 fraction of the cell cycle. A decrease in the mitochondrial transmembrane potential (??m) was also observed. Furthermore, 1 reduced the ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax and Bak, induced cytochrome c release, and increased the activity of caspase 3. The generation of reactive oxygen species (ROS) was detected in 1-treated HL-60 cells, which was attenuated by the pretreatment of cells with a free radical scavenger, N-acetylcysteine (NAC). NAC also prevented the increase of the sub-G1 fraction induced by 1. These results indicate that ramentaceone induces cell death through the ROS-mediated mitochondrial pathway. PMID:22250825

Kawiak, Anna; Zawacka-Pankau, Joanna; Wasilewska, Aleksandra; Stasilojc, Grzegorz; Bigda, Jacek; Lojkowska, Ewa

2012-01-27

305

Plumbagin induces apoptosis via the p53 pathway and generation of reactive oxygen species in human osteosarcoma cells.  

PubMed

Osteosarcoma, which is the most common primary bone tumor, occurs most frequently in adolescents. A number of studies have indicated that plumbagin (PL) (5-hydroxy-2-methyl-1, 4-naphthoquinone), a compound found in the plants of the Plumbaginaceae and Droseraceae families, possesses anticancer activity. However, its anticancer effects and mechanisms against osteosarcoma have not been explored. To determine the anticancer effect of PL on osteosarcoma cell lines MG-63 and U2OS, cell viability, apoptosis, cell cycle distribution, caspase-3 and caspase-9 activity and intracellular reactive oxygen species (ROS) generation were measured, and Western blot analyses were performed. PL significantly inhibited the growth of osteosarcoma cells, particularly U2OS cells. PL up-regulated the expression of p53 in U2OS cells and p21 in the two osteosarcoma cell lines causing cell cycle arrest by decreasing the expression of murine double minute 2 (MDM2)/cyclin B1 and cyclin D1. Furthermore, PL altered the ratio of Bax/Bcl-2, and may have triggered the mitochondrial apoptotic pathway, resulting in caspase-3 and caspase-9 activation. We also found that PL induced the generation of ROS in osteosarcoma cell lines. To conclude, PL exerted anticancer activity on osteosarcoma cells by inducing pro-apoptotic signaling and modulating the intracellular ROS that causes induction of apoptosis. These effects may relate to the p53 status. PMID:21993662

Tian, Linqiang; Yin, Delong; Ren, Ye; Gong, Chen; Chen, Anmin; Guo, Feng-Jin

2012-01-01

306

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.

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

307

Antidermatophyte and antimelanogenesis compound from Eleutherine americana grown in Indonesia.  

PubMed

An active compound from the bulb of Eleutherine americana L. Merr. (Iridaceae) collected from East Kalimantan, Indonesia, was tested for its antidermatophyte and antimelanogenesis activity. Antifungal assay-directed fractionation of the n-hexane-soluble fraction of the methanolic extract of the bulb of E. americana led to the isolation of 1 as an active compound. The compound was identified as the naphthoquinone eleutherin by EI-MS and (1)H-, (13)C-, and two-dimensional NMR analyses. Antidermatophyte assay of 1 at concentrations of 10, 20, 40, 60, and 80 microg/disk and myconazole, a commercial antidermatophyte, at 10 microg/disk displayed 7, 8, 13, 16, 17, and 14 mm of inhibition zone against Trichophyton mentagrophytes, respectively. In a melanin formation inhibition assay, compound 1 displayed potent antimelanogenesis activity at 5 ppm with low toxicity compared with arbutin, a commercial skin-whitening agent. The results showed the high potential of 1, an active compound from E. americana, to be applied as an antidermatophyte and antimelanogenesis agent. PMID:20155402

Kusuma, Irawan Wijaya; Arung, Enos Tangke; Rosamah, Enih; Purwatiningsih, Sri; Kuspradini, Harlinda; Syafrizal; Astuti, Juli; Kim, Yong-Ung; Shimizu, Kuniyoshi

2010-04-01

308

Lower intracellular hydrogen peroxide levels in cells overexpressing CuZn-superoxide dismutase  

PubMed Central

Transfection of V79 Chinese hamster cells produced clones in which CuZn-superoxide dismutase (CuZn-SOD) activities were 2.2- to 3.5-fold higher than in the parental cells. An overall reduction of antioxidant enzyme activities and both total and oxidized glutathione levels had been found in these clones. Aconitase activities in these cells were determined to indirectly measure the O2? steady-state levels. As expected, in cells overexpressing CuZn-SOD, both total and cytosolic aconitase activities have increased. Because these clones showed reduced oxidized glutathione contents, it is unlikely that they present higher H2O2 steady-state levels as a consequence of the higher SOD levels. This was confirmed by measuring H2O2 steady-state levels in cells by flow cytometric analysis of 2?,7?-dichlorofluorescein diacetate-treated cells. Despite the decreased antioxidant defenses, three of the clones overexpressing CuZn-SOD showed reduced H2O2 steady-state levels. These reduced H2O2 steady-state levels were found even when the cells were treated with the O2? generator 2,3-dimethoxy-1,4-naphthoquinone. These data provide in vivo support for the hypothesis proposed by Liochev and Fridovich [Liochev, S. I. & Fridovich, I. (1994) Free Radical Biol. Med. 16, 29–33] that O2? dismutation prevents the formation of higher H2O2 levels by other reactions.

Teixeira, Henrique D.; Schumacher, Robert I.; Meneghini, Rogerio

1998-01-01

309

Catabolism of phloroglucinol by the rumen anaerobe coprococcus.  

PubMed

A rumen isolate, Coprococcus, sp. Pe(1)5, was found to carry phloroglucinol reductase, which catalyzed the initial step in the breakdown of phloroglucinol. The organism uses phloroglucinol as the sole source of carbon and energy when grown in the absence of oxygen. Induced levels of enzyme were detected in cells grown either on phloroglucinol or on other carbon sources in the presence of limiting quantities of phloroglucinol. Although the organism is a strict anaerobe, the enzyme from anaerobically grown cells was insensitive to air. The partially purified enzyme required reduced nicotinamide adenine dinucleotide phosphate as an electron donor and was specific for phloroglucinol. However, partial enzyme activity (14 to 17%) was also detected in the presence of 2-methyl-1,4-naphthoquinone but not in the presence of several other phenolic compounds. The enzyme exhibited a higher affinity for phloroglucinol than for reduced nicotinamide adenine dinucleotide phosphate, with K(m) values of 3.0 x 10 M and 29.0 x 10 M, respectively. The optimum pH for maximal enzyme activity was 7.4, and the molecular weight of the native protein was about 130,000, as determined by the Sephadex gel filtration technique. PMID:16345897

Patel, T R; Jure, K G; Jones, G A

1981-12-01

310

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

311

Vinyl ketone reduction by three distinct Gluconobacter oxydans 621H enzymes.  

PubMed

Three cytosolic NADPH-dependent flavin-associated proteins (Gox2107, Gox0502, and Gox2684) from Gluconobacter oxydans 621H were overproduced in Escherichia coli, and the recombinant enzymes were purified and characterized. Apparent native molecular masses of 65.2, 78.2, and 78.4 kDa were observed for Gox2107, Gox0502, and Gox2684, corresponding to a trimeric structure for Gox2107 and dimers for Gox0502 and Gox2684. Analysis of flavin content revealed Gox2107 was flavin adenine dinucleotide dependent, whereas Gox0502 and Gox2684 contained flavin mononucleotide. The enzymes were able to reduce vinyl ketones and quinones, reducing the olefinic bond of vinyl ketones as shown by (1)H nuclear magnetic resonance. Additionally, Gox0502 and Gox2684 stereospecifically reduced 5S-(+)-carvone to 2R,5S-dihydrocarvone. All enzymes displayed highest activities with 3-butene-2-one and 1,4-naphthoquinone. Gox0502 and Gox2684 displayed a broader substrate spectrum also reducing short-chain alpha-diketones, whereas Gox2107 was most catalytically efficient. PMID:18629490

Schweiger, Paul; Gross, Harald; Wesener, Shane; Deppenmeier, Uwe

2008-10-01

312

Studies on Aristolochia III. Isolation and biological evaluation of constituents of Aristolochia indica roots for fertility-regulating activity.  

PubMed

An ethanol extract of Aristolochia indica roots decreased fertility in both rats and hamsters when administered postcoitally (days 1-10 and 1-6, respectively). Petroleum ether (A), CHCl3 (B), and aqueous (C) fractions, tested similarly in rats, were inactive and/or toxic. Partition of fraction B afforded non-acidic (D) and acidic (E) fractions. Savinin (1), isolated from fraction D and not previously reported from the Aristolochiaceae , was inactive when administered postcoitally to rats. Aristolochic acid-I (2), reported previously from A. indica and isolated from fraction E, was inactive when administered postcoitally to rats and toxic when administered postcoitally to hamsters. (12S)-7,12- Secoishwaran -12-ol (3), previously reported from A. indica and isolated from fraction A, did not interrupt pregnancy when administered to mice on day 6 of pregnancy. Four additional compounds, aristolic acid (4) [prepared from aristolochic acid-I (2)], methyl aristolate (5) [prepared by methylating aristolic acid (4)], and cis- and trans-p-coumaric acid (both oblate commercially), were similarly tested in mice and found to be inactive. Aristolic acid (4), and the cis- and trans-p-coumaric acids also were inactive when administered postcoitally (days 1-10) to rats. Seven compounds reported previously from A. indica were also isolated, as were a new naphthoquinone, aristolindiquinone (6) (fraction E), and magnoflorine (fraction C). PMID:6539809

Che, C T; Ahmed, M S; Kang, S S; Waller, D P; Bingel, A S; Martin, A; Rajamahendran, P; Bunyapraphatsara, N; Lankin, D C; Cordell, G A

1984-01-01

313

Molecular pharmacology and antitumor activity of palmarumycin based inhibitors of thioredoxin reductase.  

PubMed Central

The cytosolic thioredoxin (Trx) redox system comprising Trx-1 and the NADPH dependent thioredoxin reductase -1 reductase (TrxR-1) is an important regulator of cell growth and survival. Trx-1 is overexpressed in many human tumors where it is associated with increased cell proliferation, decreased apoptosis and decreased patient survival. We hypothesized that TrxR-1 provides a target to inhibit the activity of overexpressed Trx-1 for the development of novel anticancer agents. We found that the naphthoquinone spiroketal fungal metabolite palmarumycin CP1 is a potent inhibitor of TrxR-1, but attempts to exploit the activity of palmarumycin CP1 analogs as antitumor agents in vivo were hampered by their insolubility. We have therefore developed PX-916, a water soluble prodrug of a palmarumycin CP1 analog. PX-916 rapidly releases the parent compound at physiological pH and in plasma, but is stable at acid pH allowing its iv administration. PX-916 is a potent inhibitor of purified human TrxR-1 and of TrxR-1 activity in cells and tumor xenografts when administered to mice, and inhibits the down stream targets of Trx-1 signaling, HIF-1? and VEGF, in tumors. PX-916 showed excellent antitumor activity against several animal tumor models with some cures. Thus, the study demonstrates that water soluble inhibitors of TrxR-1 such as PX-916 can block Trx-1 signaling in tumors producing marked inhibition of tumor growth.

Wipf, Peter; Lynch, Stephen M.; Birmingham, Anne; Kirkpatrick, D. Lynn

2006-01-01

314

A novel lung slice system with compromised antioxidant defenses  

SciTech Connect

In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 {mu}M) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP{sup +}, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of {sup 14}CO{sub 2} from D-({sup 14}C(U))-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.

Hardwick, S.J.; Adam, A.; Cohen, G.M. (Univ. of London (England)); Smith, L.L. (Imperial Chemical Industries PLC, Cheshire (England))

1990-04-01

315

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

316

Expression patterns of Glutathione Transferase Gene (GstI) in maize seedlings under juglone-induced oxidative stress.  

PubMed

Juglone (5-hydroxy-1,4-naphthoquinone) has been identified in organs of many plant species within Juglandaceae family. This secondary metabolite is considered as a highly bioactive substance that functions as direct oxidant stimulating the production of reactive oxygen species (ROS) in acceptor plants. Glutathione transferases (GSTs, E.C.2.5.1.18) represent an important group of cytoprotective enzymes participating in detoxification of xenobiotics and limiting oxidative damages of cellular macromolecules. The purpose of this study was to investigate the impact of tested allelochemical on growth and development of maize (Zea mays L.) seedlings. Furthermore, the effect of juglone-induced oxidative stress on glutathione transferase (GstI) gene expression patterns in maize seedlings was recorded. It was revealed that 4-day juglone treatment significantly stimulated the transcriptional activity of GstI in maize seedlings compared to control plants. By contrast, at the 6th and 8th day of experiments the expression gene responses were slightly lower as compared with non-stressed seedlings. Additionally, the specific gene expression profiles, as well as the inhibition of primary roots and coleoptile elongation were proportional to juglone concentrations. In conclusion, the results provide strong molecular evidence that allelopathic influence of juglone on growth and development of maize seedlings may be relevant with an induction of oxidative stress in acceptor plants. PMID:22174645

Sytykiewicz, Hubert

2011-01-01

317

Effect of initial carbon sources on the electrochemical detection of glucose by Gluconobacter oxydans.  

PubMed

An electrochemical system consisted of Gluconobacter oxydans as a microorganism and 2-hydroxy-1,4-naphthoquinone (HNQ) as a mediator has been setup to examine the effect of initial carbon sources on the detection of glucose. Catalytic current due to the oxidation of glucose was observed only when both G. oxydans and HNQ were present. From amperometric measurements, it was found that the sensitivity strongly depended on the initial carbon sources. The sensitivity was highest for the cells cultured in a fructose-containing medium and decreased in the order, mannitol > sucrose > glucose > galactose > glycerol. The difference in sensitivity was explained by considering the current rising pattern at an initial stage of a microbial fuel cell constructed with the same components. The rising time, not the fuel cell efficiency, could directly be related to the sensitivity order. A sensor where G. oxydans was confined at the vicinity of the electrode by the semipermeable membrane was constructed. A linear response over a millimolar range of glucose concentration was observed with a cell grown in galactose-containing medium. This work demonstrates that the initial carbon source play an important role on glucose sensoring and should be considered in a real application. PMID:12160615

Lee, Sung Ae; Choi, Youngjin; Jung, Seunho; Kim, Sunghyun

2002-09-01

318

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 0.03ngmL(-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

319

Electro-Fenton and photoelectro-Fenton degradations of the drug beta-blocker propranolol using a Pt anode: identification and evolution of oxidation products.  

PubMed

The beta-blocker propranolol hydrochloride has been degraded by electrochemical advanced oxidation processes like electro-Fenton (EF) and photoelectro-Fenton (PEF) using a single cell with a Pt anode and an air diffusion cathode (ADE) for H(2)O(2) electrogeneration and a combined system containing the above Pt/ADE pair coupled in parallel to a Pt/carbon-felt (CF) cell. Organics are mainly oxidized with hydroxyl radical (OH) formed from Fenton's reaction between added Fe(2+) and electrogenerated H(2)O(2). The PEF treatment in Pt/ADE-Pt/CF system yields almost total mineralization because OH production is enhanced by Fe(2+) regeneration from Fe(3+) reduction at the CF cathode and Fe(III) complexes with generated carboxylic acids are rapidly photodecarboxylated under UVA irradiation. Lower mineralization degree is found for PEF in Pt/ADE cell due to the little influence of UVA light on Fe(2+) regeneration. The homologous EF processes are much less potent as a result of the persistence of Fe(III)-carboxylate complexes. Aromatic intermediates such as 1-naphthol, 1,4-naphthoquinone and phthalic acid and generated carboxylic acids such as pyruvic, glycolic, malonic, maleic, oxamic, oxalic and formic are identified. While chloride ion remains stable, NH(4)(+) and NO(3)(-) ions are released to the medium. A reaction sequence for propranolol hydrochloride mineralization is proposed. PMID:21056539

Isarain-Chávez, Eloy; Cabot, Pere Lluís; Centellas, Francesc; Rodríguez, Rosa María; Arias, Conchita; Garrido, José Antonio; Brillas, Enric

2011-01-30

320

Synthesis of 1,2-annulated and 1,2-unsubstituted pyrrolo[2,1,5-de]quinolizin-5-ones (cycl[3.3.2]azin-5-ones) via [3+2] cycloadditions of 1-oxoquinolizinium ylides with cyclic alkenes.  

PubMed

1,2-Annulated pyrrolo[2,1,5-de]quinolizin-5-ones (cycl[3.3.2]azin-5-ones) 6a-6k, 8a-8b and 9 have been synthesized by one pot tandem reactions of 2-acetyl-N-phenacylpyridinium bromides (1a-1d) with electron-deficient cyclic alkenes (N-alkyl(aryl)maleimides, benzoquinones and naphthoquinone) in the presence of sodium carbonate as a base and tetrakispyridinecobalt(II) dichromate (TPCD) as an oxidant. These products are formed by 1.3-dipolar cycloaddition of the 1-oxoquinolizinium ylides generated in situ from 1a-1d with the alkene followed by dehydrogenation of the primary cycloadduct under the action of TPCD. Similar reactions of the ylides generated in situ from 1a-1f with maleic anhydride gave the 1,2-unsubstituted pyrrolo[2,1,5-de]quinolizin-5-ones 7a-7f via oxidative bisdecarboxylation and dehydrogenation of the primary cycloadducts under the action of TPCD. PMID:20740245

Liu, Yun; Hu, Hua-You; Zhang, Yan; Hu, Hong-Wen; Xu, Jian-Hua

2010-11-01

321

Effects of several quinones on insulin aggregation  

PubMed Central

Protein misfolding and aggregation are associated with more than twenty diseases, such as neurodegenerative diseases and metabolic diseases. The amyloid oligomers and fibrils may induce cell membrane disruption and lead to cell apoptosis. A great number of studies have focused on discovery of amyloid inhibitors which may prevent or treat amyloidosis diseases. Polyphenols have been extensively studied as a class of amyloid inhibitors, with several polyphenols under clinical trials as anti-neurodegenerative drugs. As oxidative intermediates of natural polyphenols, quinones widely exist in medicinal plants or food. In this study, we used insulin as an amyloid model to test the anti-amyloid effects of four simple quinones and four natural anthraquinone derivatives from rhubarb, a traditional herbal medicine used for treating Alzheimer's disease. Our results demonstrated that all eight quinones show inhibitory effects to different extent on insulin oligomerization, especially for 1,4-benzoquinone and 1,4-naphthoquinone. Significantly attenuated oligomerization, reduced amount of amyloid fibrils and reduced hemolysis levels were found after quinones treatments, indicating quinones may inhibit insulin from forming toxic oligomeric species. The results suggest a potential action of native anthraquinone derivatives in preventing protein misfolding diseases, the quinone skeleton may thus be further explored for designing effective anti-amyloidosis compounds.

Gong, Hao; He, Zihao; Peng, Anlin; Zhang, Xin; Cheng, Biao; Sun, Yue; Zheng, Ling; Huang, Kun

2014-01-01

322

A new type of pterocarpanquinone that affects Toxoplasma gondii tachyzoites in vitro.  

PubMed

Toxoplasma gondii, the agent of Toxoplasmosis, is an obligate intracellular protozoan able to infect a wide range of vertebrate cells, including nonprofessional and professional phagocytes. Therefore, drugs must have intracellular activities in order to control this parasite. The most common therapy for Toxoplasmosis is the combination of sulfadiazine and pyrimethamine. This treatment is associated with adverse reactions, thus, the development of new drugs is necessary. In previous studies, naphthoquinone derivatives showed anti-cancer activity functioning as agents capable of acting on groups of DNA, preventing cancer cells duplication. These derivatives also display anti-parasitic activity against Plasmodium falciparum and Leishmania amazonensis. The derivative pterocarpanquinone tested in this work resulted from the molecular hybridization between pterocarpans and naphtoquinone that presents anti-tumoral and anti-parasitic activities of lapachol. The aim of this work was to determine if this derivative is able to change T. gondii growth within LLC-MK2 cells. The drug did not arrest host cell growth, but was able to decrease the infection index of T. gondii with an IC(50) of 2.5 ?M. Scanning and transmission electron microscopy analysis showed morphological changes of parasites including membrane damage. The parasite that survived tended to encyst as seen by Dolichos biflorus lectin staining and Bag-1 expression. These results suggest that pterocarpanquinones are drugs potentially important for the killing and encystment of T. gondii. PMID:22177332

Portes, Juliana de Araujo; Netto, Chaquip Daher; da Silva, Alcides José Monteiro; Costa, Paulo Roberto Ribeiro; DaMatta, Renato Augusto; dos Santos, Thiago Alves Teixeira; De Souza, Wanderley; Seabra, Sergio Henrique

2012-05-25

323

Homogeneous purification and characterization of LePGT1--a membrane-bound aromatic substrate prenyltransferase involved in secondary metabolism of Lithospermum erythrorhizon.  

PubMed

Membrane-bound type prenyltransferases for aromatic substrates play crucial roles in the biosynthesis of various natural compounds. Lithospermum erythrorhizon p-hydroxybenzoate: geranyltransferase (LePGT1), which contains multiple transmembrane ?-helices, is involved in the biosynthesis of a red naphthoquinone pigment, shikonin. Taking LePGT1 as a model membrane-bound aromatic substrate prenyltransferase, we utilized a baculovirus-Sf9 expression system to generate a high yield LePGT1 polypeptide, reaching ~ 1000-fold higher expression level compared with a yeast expression system. Efficient solubilization procedures and biochemical purification methods were developed to extract LePGT1 from the membrane fraction of Sf9 cells. As a result, 80 ?g of LePGT1 was purified from 150 mL culture to almost homogeneity as judged by SDS/PAGE. Using purified LePGT1, enzymatic characterization, e.g. substrate specificity, divalent cation requirement and kinetic analysis, was done. In addition, inhibition experiments revealed that aromatic compounds having two phenolic hydroxyl groups effectively inhibited LePGT1 enzyme activity, suggesting a novel recognition mechanism for aromatic substrates. As the first example of solubilization and purification of this membrane-bound protein family, the methods established in this study will provide valuable information for the precise biochemical characterization of aromatic prenyltransferases as well as for crystallographic analysis of this novel enzyme family. PMID:23490165

Ohara, Kazuaki; Mito, Koji; Yazaki, Kazufumi

2013-06-01

324

Shikonin directly targets mitochondria and causes mitochondrial dysfunction in cancer cells.  

PubMed

Chemotherapy is a mainstay of cancer treatment. Due to increased drug resistance and the severe side effects of currently used therapeutics, new candidate compounds are required for improvement of therapy success. Shikonin, a natural naphthoquinone, was used in traditional Chinese medicine for the treatment of different inflammatory diseases and recent studies revealed the anticancer activities of shikonin. We found that shikonin has strong cytotoxic effects on 15 cancer cell lines, including multidrug-resistant cell lines. Transcriptome-wide mRNA expression studies showed that shikonin induced genetic pathways regulating cell cycle, mitochondrial function, levels of reactive oxygen species, and cytoskeletal formation. Taking advantage of the inherent fluorescence of shikonin, we analyzed its uptake and distribution in live cells with high spatial and temporal resolution using flow cytometry and confocal microscopy. Shikonin was specifically accumulated in the mitochondria, and this accumulation was associated with a shikonin-dependent deregulation of cellular Ca(2+) and ROS levels. This deregulation led to a breakdown of the mitochondrial membrane potential, dysfunction of microtubules, cell-cycle arrest, and ultimately induction of apoptosis. Seeing as both the metabolism and the structure of mitochondria show marked differences between cancer cells and normal cells, shikonin is a promising candidate for the next generation of chemotherapy. PMID:23118796

Wiench, Benjamin; Eichhorn, Tolga; Paulsen, Malte; Efferth, Thomas

2012-01-01

325

Shikonin shortens the circadian period: possible involvement of Top2 inhibition.  

PubMed

The naphthoquinone pigment, shikonin, is a natural product derived from Lithospermum erythrorhizon and an active component of a Chinese traditional herbal therapeutic. We identified shikonin as a candidate for shortening the circadian period using real-time reporter gene assays based on NIH3T3-derived stable reporter cells. Period length that became shortened in cells incubated with shikonin or etoposide reverted to that of control cells after continued incubation without these compounds. These findings indicated that shikonin and etoposide shorten the circadian period reversibly and through similar mechanisms. Topoisomerase II (Top2)-specific decatenation assays confirmed that shikonin, liker etoposide, is a Top2 inhibitor. Shikonin was incorporated into the nucleus and Top2 was located in the Bmal1 promoter, suggesting the relationship between Bmal1 transcription and Top2 inhibition. Top2a siRNA also shortened period length, suggesting that Top2 is involved in this process. Promoter assays showed that Top2a siRNA, etoposide and shikonin reduce Bmal1 promoter activity. These findings indicated that Top2 is involved in Bmal1 transcription and influences the circadian period, and that shikonin is a novel contributor to the control of period length in mammalian cells. PMID:24321095

Ogawa, Yoshikatsu; Kawano, Yasuhiro; Yamazaki, Yoshimitsu; Onishi, Yoshiaki

2014-01-01

326

Shikonin Directly Targets Mitochondria and Causes Mitochondrial Dysfunction in Cancer Cells  

PubMed Central

Chemotherapy is a mainstay of cancer treatment. Due to increased drug resistance and the severe side effects of currently used therapeutics, new candidate compounds are required for improvement of therapy success. Shikonin, a natural naphthoquinone, was used in traditional Chinese medicine for the treatment of different inflammatory diseases and recent studies revealed the anticancer activities of shikonin. We found that shikonin has strong cytotoxic effects on 15 cancer cell lines, including multidrug-resistant cell lines. Transcriptome-wide mRNA expression studies showed that shikonin induced genetic pathways regulating cell cycle, mitochondrial function, levels of reactive oxygen species, and cytoskeletal formation. Taking advantage of the inherent fluorescence of shikonin, we analyzed its uptake and distribution in live cells with high spatial and temporal resolution using flow cytometry and confocal microscopy. Shikonin was specifically accumulated in the mitochondria, and this accumulation was associated with a shikonin-dependent deregulation of cellular Ca2+ and ROS levels. This deregulation led to a breakdown of the mitochondrial membrane potential, dysfunction of microtubules, cell-cycle arrest, and ultimately induction of apoptosis. Seeing as both the metabolism and the structure of mitochondria show marked differences between cancer cells and normal cells, shikonin is a promising candidate for the next generation of chemotherapy.

Wiench, Benjamin; Eichhorn, Tolga; Paulsen, Malte; Efferth, Thomas

2012-01-01

327

?,?-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species  

PubMed Central

Shikonin, a naphthoquinone derivative, has been shown to possess antitumor activity. In the present study, the effects of shikonin and its analog, ?,?-dimethylacrylshikonin, were investigated as radiosensitizers on the human colon cancer cell line, HCT-116. Shikonin and, to a greater extent, its analog-induced apoptosis of HCT-116 cells further synergistically potentiated the induction of apoptosis when combined with ionizing radiation (IR) treatment. Shikonins also stimulated an increase in reactive oxygen species (ROS) production and IR-induced DNA damage. Pre-treatment with the ROS scavenger, N-acetylcysteine, suppressed the enhancement of IR-induced DNA damage and apoptosis stimulated by shikonins, indicating that shikonins exert their radiosensitizing effects through ROS upregulation. The radiosensitizing effect of shikonins was also examined in vivo using the xenograft mouse model. Consistent with the in vitro results, injection of ?,?-dimethylacrylshikonin combined with IR treatment significantly suppressed tumor growth of the HCT-116 xenograft. Taken together, the results show that ?,?-dimethylacrylshikonin is a promising agent for developing an improved strategy for radiotherapy against tumors.

KWAK, SEO-YOUNG; JEONG, YOUN KYOUNG; KIM, BU-YEON; LEE, JI YOUNG; AHN, HYUN-JOO; JEONG, JAE-HOON; KIM, MI-SOOK; KIM, JOON; HAN, YOUNG-HOON

2014-01-01

328

Shikonin exerts anti-inflammatory effects in a murine model of lipopolysaccharide-induced acute lung injury by inhibiting the nuclear factor-kappaB signaling pathway.  

PubMed

Shikonin, an analog of naphthoquinone pigments isolated from the root of Lithospermum erythrorhyzon, was recently reported to exert beneficial anti-inflammatory effects both in vivo and in vitro. The present study aimed to investigate the potential therapeutic effect of shikonin in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Dexamethasone was used as a positive control to evaluate the anti-inflammatory effect of shikonin in the study. Pretreatment with shikonin (intraperitoneal injection) significantly inhibited LPS-induced increases in the macrophage and neutrophil infiltration of lung tissues and markedly attenuated myeloperoxidase activity. Furthermore, shikonin significantly reduced the concentrations of TNF-?, IL-6 and IL-1? in bronchoalveolar lavage fluid induced by LPS. Compared with the LPS group, lung histopathologic changes were less pronounced in the shikonin-pretreated mice. Additionally, Western blotting results showed that shikonin efficiently decreased nuclear factor-kappaB (NF-?B) activation by inhibiting the degradation and phosphorylation of I?B?. These results suggest that shikonin exerts anti-inflammatory properties in LPS-mediated ALI, possibly through inhibition of the NF-?B signaling pathway, which mediates the expression of pro-inflammatory cytokines. Shikonin may be a potential agent for the prophylaxis of ALI. PMID:23651796

Liang, Dejie; Sun, Yong; Shen, Yongbin; Li, Fengyang; Song, Xiaojing; Zhou, Ershun; Zhao, Fuyi; Liu, Zhicheng; Fu, Yunhe; Guo, Mengyao; Zhang, Naisheng; Yang, Zhengtao; Cao, Yongguo

2013-08-01

329

Integration of Different "-omics" Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells.  

PubMed

Hematological malignancies frequently have a poor prognosis and often remain incurable. Drug resistance, severe side effects, and relapse are major problems of currently used drugs, and new candidate compounds are required for improvement of therapy success. The naphthoquinone shikonin derived from the Chinese medicinal herb, Lithospermum erythrorhizon, is a promising candidate for the next generation of chemotherapy. The basal cellular mechanism of shikonin is the direct targeting of mitochondria. Cytotoxicity screenings showed that the compound is particularly effective against leukemia cells suggesting an additional cellular mechanism. mRNA and miRNA microarrays were used to analyze changes in gene expression in leukemia cells after shikonin treatment and combined with stable-isotope dimethyl labeling for quantitative proteomics. The integration of bioinformatics and the three "-omics" assays showed that the PI3K-Akt-mTOR pathway was affected by shikonin. Deregulations of this pathway are frequently associated with cancerogenesis, especially in a wide range of hematological malignancies. The effect on the PI3K-Akt-mTOR axis was validated by demonstrating a decreased phosphorylation of Akt and a direct inhibition of the IGF1R kinase activity after shikonin treatment. Our results indicate that inhibiting the IGF1R-Akt-mTOR signaling cascade is a new cellular mechanism of shikonin strengthening its potential for the treatment of hematological malignancies. PMID:23861714

Wiench, Benjamin; Chen, Yet-Ran; Paulsen, Malte; Hamm, Rebecca; Schröder, Sven; Yang, Ning-Sun; Efferth, Thomas

2013-01-01

330

Integration of Different "-omics" Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells  

PubMed Central

Hematological malignancies frequently have a poor prognosis and often remain incurable. Drug resistance, severe side effects, and relapse are major problems of currently used drugs, and new candidate compounds are required for improvement of therapy success. The naphthoquinone shikonin derived from the Chinese medicinal herb, Lithospermum erythrorhizon, is a promising candidate for the next generation of chemotherapy. The basal cellular mechanism of shikonin is the direct targeting of mitochondria. Cytotoxicity screenings showed that the compound is particularly effective against leukemia cells suggesting an additional cellular mechanism. mRNA and miRNA microarrays were used to analyze changes in gene expression in leukemia cells after shikonin treatment and combined with stable-isotope dimethyl labeling for quantitative proteomics. The integration of bioinformatics and the three “-omics” assays showed that the PI3K-Akt-mTOR pathway was affected by shikonin. Deregulations of this pathway are frequently associated with cancerogenesis, especially in a wide range of hematological malignancies. The effect on the PI3K-Akt-mTOR axis was validated by demonstrating a decreased phosphorylation of Akt and a direct inhibition of the IGF1R kinase activity after shikonin treatment. Our results indicate that inhibiting the IGF1R-Akt-mTOR signaling cascade is a new cellular mechanism of shikonin strengthening its potential for the treatment of hematological malignancies.

Chen, Yet-Ran; Paulsen, Malte; Hamm, Rebecca; Schroder, Sven; Yang, Ning-Sun; Efferth, Thomas

2013-01-01

331

Beneficial effect of shikonin on experimental colitis induced by dextran sulfate sodium in BALB/c mice.  

PubMed

The naphthoquinone shikonin, a major component of the root of Lithospermum erythrorhizon, now is studied as an anti-inflammatory agent in the treatment of ulcerative colitis (UC). Acute UC was induced in Balb/C mice by oral administration of 5% dextran sodium sulfate (DSS). The disease activity index was evaluated, and a histologic study was carried out. Orally administered shikonin reduces induced UC in a dose-dependent manner, preventing the shortening of the colorectum and decreasing weight loss by 5% while improving the appearance of feces and preventing bloody stools. The disease activity index score was much lower in shikonin-treated mice than in the colitic group, as well as the myeloperoxidase activity. The expression of cyclooxygenase-2 was reduced by 75%, activation of NF-?B was reduced by 44%, and that of pSTAT-3 by 47%, as well as TNF-?, IL-1?, and IL-6 production. Similar results were obtained in primary macrophages culture. This is the first report of shikonin's ability to attenuate acute UC induced by DSS. Shikonin acts by blocking the activation of two major targets: NF-?B and STAT-3, and thus constitutes a promising potential therapeutic agent for the management of the inflammatory bowel disease. PMID:23346196

Andújar, Isabel; Ríos, José Luis; Giner, Rosa María; Miguel Cerdá, José; Recio, María Del Carmen

2012-01-01

332

Apoptosis induced by ?,?-dimethylacrylshikonin is associated with Bcl-2 and NF-?B in human breast carcinoma MCF-7 cells  

PubMed Central

?,?-dimethylacrylshikonin (DA) is a natural naphthoquinone derivative compound of Lithospermum erythrorhizon with various biological activities. The present study aimed to investigate the inhibitory effects and underlying mechanisms of DA in human breast carcinoma MCF-7 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that DA inhibited the proliferation of MCF-7 cells in a dose- and time-dependent manner. The half maximal inhibitory concentration of DA with regard to the proliferation of MCF-7 cells was 0.050±0.016 mM. The characteristics of cell apoptosis, including cell shrinkage, nuclear pyknosis and chromatin condensation, were all observed in DA-treated cells. DA decreased the expression levels of Bcl-2 and increased the expression of Bax and caspase-3 compared with those in the control. DA inhibited the activity of the nuclear factor (NF)-?B pathway, by downregulating the expression of the p65 subunit, and inhibited the I?b phosphorylation. DA inhibits the proliferation of MCF-7 cells in vitro by inducing apoptosis through the downregulation of Bcl-2, upregulation of Bax and partial inactivation of the NF-?B pathway.

XIONG, YAO; MA, XIU-YING; ZHANG, ZIRAN; SHAO, ZHEN-JUN; ZHANG, YUAN-YUAN; ZHOU, LI-MING

2013-01-01

333

Effects of KTJ740, a novel antithrombotic agent, on platelet-derived growth factor-induced rat aortic smooth muscle cell proliferation and cell cycle progression.  

PubMed

Hyperproliferation of platelet-derived growth factor (PDGF)-BB-induced vascular smooth muscle cell (VSMC) is a hallmark of atherosclerosis and related vascular disorders. In the previous study, we reported that KTJ740 [2-chloro-3-(4-(ethylcarboxy)-phenyl)-amino-1,4-naphthoquinone], a newly synthesized vitamin K derivative, has potent antithrombotic effects in mice and antiplatelet activity in vitro and ex vivo. In the present study, we have tested that KTJ740 could inhibit PDGF-BB-stimulated VSMC proliferation. We have examined the potential inhibitory effect of this compound on rat aortic smooth muscle cells (RASMCs). Our results show that this compound significantly inhibits PDGF-BB-stimulated RASMC number and DNA synthesis in a concentration-dependent manner. Furthermore, we have examined its effect on cell cycle progression by flow cytometry. KTJ740 treatment resulted in a significant arrest in cell cycle progression of RASMCs induced by PDGF-BB, and this effect was achieved by suppressing activation of PDGF-beta receptor (PDGF-Rbeta) tyrosine kinase pathway. These results suggest that a possibility of KTJ740 can be a potential agent to control vascular disorders and its antiproliferative mechanism may be mediated through PDGF-Rbeta tyrosine kinase-dependent signaling pathway. PMID:17513946

Kim, Tack-Joong; Jeon, Jinseon; Jin, Yong-Ri; Son, Dong-Ju; Yoo, Hwan-Soo; Hong, Jin-Tae; Ryu, Chung-Kyu; Shin, Hwa-Sup; Lee, Kwang-Ho; Yun, Yeo-Pyo

2007-05-01

334

Semisynthetic derivatives of purpuromycin as potential topical agents for vaginal infections.  

PubMed

Purpuromycin (1) is an antibiotic with a broad spectrum of antimicrobial activity, encompassing bacteria, fungi, and protozoa, particularly those involved in vaginal infections. With the aim of enhancing the solubility and reducing the serum binding, a chemical program of modifications was undertaken on the natural compound, and a new interesting series of derivatives at the naphthoquinone system was synthesized and evaluated as potential topical agents for vaginal infections. In particular three semisynthetic derivatives, 7'-amino (8a), 7'-methylamino (8b), 7'-ethylamino (8c), of 7'-demethoxypurpuromycin seemed to be the most promising. They were tested for in vitro activity against three of the most important vaginal pathogens and showed activity similar to that of purpuromycin against Candida isolates while they were significantly more active against Trichomonas vaginalis and Gardnerella vaginalis, which are cultured in media containing blood or serum. This is probably due to the fact that the activity of the derivatives is less antagonized by these supplements than that of purpuromycin. PMID:9083486

Trani, A; Dallanoce, C; Panzone, G; Ripamonti, F; Goldstein, B P; Ciabatti, R

1997-03-14

335

Studies on tetrachloroethene respiration in Dehalospirillum multivorans.  

PubMed

Tetrachloroethene (PCE) respiration was studied in the tetrachloroethene-utilizing anaerobe, Dehalospirillum multivorans, with respect to localization of the catabolic enzymes, the electron carriers potentially involved in electron transport, and the response to ionophores and specific inhibitors. Hydrogenase and formate dehydrogenase were recovered in the periplasmic cell fraction and were membrane-associated. Electron-accepting tetrachloroethene dehalogenase was found in the cytoplasmic fraction. In the PCE dehalogenase assay, only artificial electron donors with a standard redox potential of D. multivorans (Eo' = -445 mV) could serve as electron donor for PCE reduction. However, the reaction rate with ferredoxin was only 1% of that with methyl viologen, whereas the pyruvate-ferredoxin oxidoreductase exhibited almost the same reaction rates with methyl viologen and ferredoxin as electron acceptors for pyruvate oxidation. Reduced menadione (2-methyl-1, 4-naphthoquinone) did not serve as electron donor in the PCE dehalogenase reaction. 2-Heptyl-4-hydroxyquinoline-N-oxide (HOQNO) had no significant effect on PCE dechlorination in cell suspensions and in crude extracts. Whole cells catalyzed the reductive dechlorination of PCE with H2 or formate as electron donors. The dechlorination in cell suspensions rather than in cell extracts was inhibited by the ionophores carbonylcyanide-p-(trifluoromethoxy)phenylhydrazone (FCCP) and tetrachlorosalicylanilide (TCS), indicating that a membrane potential and/or a pH gradient may be required for the reaction in vivo. PMID:9082914

Miller, E; Wohlfarth, G; Diekert, G

1996-12-01

336

Effects of 9,10-dihydroxy-4,4-dimethyl-5,8-dihydro-1(4H)-anthracenone derivatives on tumor cell respiration.  

PubMed

A series of tricyclic hydroquinones, incorporating a carbonyl group in the ortho position relative to the phenol function, were tested as inhibitors of oxygen uptake against the TA3 mouse carcinoma cell line and its multidrug-resistant variant TA3-MTX-R. The title compound, which proved to be the most active one, also exhibited low micromolar dose-dependent growth inhibition of the human tumor U937 cell line (human monocytic leukemia). A tentative structure-activity relationship is proposed for these substances. A comparison between the cytotoxicities of the title compound and 4,4-dimethyl-5,8-dihydroxynaphthalene-1-one, with their activities as inhibitors of oxygen uptake by the TA3-MTX-R cell line, is presented. Also, the inhibition of oxygen uptake by 6-(4-methylpent-3-enyl)-1,4-naphthoquinone was determined and compared with its reported cytotoxicity toward P-388 (murine lymphocytic leukemia), A-549 (human lung carcinoma), HT-29 (human colon carcinoma), and MEL-28 (human melanoma) cells. The inhibition of oxygen uptake by TA3-MTX-R cells is useful as a quick test for preliminary screening of possible anticancer activity. PMID:16504517

Araya-Maturana, Ramiro; Cardona, Wilson; Cassels, Bruce K; Delgado-Castro, Tomás; Ferreira, Jorge; Miranda, Dante; Pavani, Mario; Pessoa-Mahana, Hernán; Soto-Delgado, Jorge; Weiss-López, Boris

2006-07-01

337

Effects of Salvia officinalis and Thymus vulgaris on oxidant-induced DNA damage and antioxidant status in HepG2 cells.  

PubMed

Salvia officinalis (SO) and Thymus vulgaris (TV) are medicinal plants well known for their curative powers. However, the molecular mechanisms responsible for these abilities of sage and thyme have not been fully understood yet. In this study we investigated the composition and the quantitative estimation of plant extracts, the protective effects of plant extracts against hydrogen peroxide- and 2,3-dimethoxy-1,4-naphthoquinone-induced DNA damage, and levels of enzymatic and non-enzymatic antioxidants (superoxide dismutase, glutathione peroxidase, glutathione) in human HepG2 cells. To measure antioxidative activity of plant extracts we used three assays: 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The results showed that the oxidant-induced DNA lesions were significantly reduced in cells pre-treated with the plant extracts studied. The observed DNA-protective activity could be explained by both elevation of GPx activity in cells pre-treated with SO and TV and antioxidant activity of SO and TV. PMID:23870948

Kozics, Katarína; Klusová, Veronika; Sran?íková, Annamária; Mu?aji, Pavol; Slame?ová, Darina; Hunáková, Lubica; Kusznierewicz, Barbara; Horváthová, Eva

2013-12-01

338

Vitamins K interact with N-terminus ?-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and ?-synuclein.  

PubMed

In the last decades, a series of compounds, including quinones and polyphenols, has been described as having anti-fibrillogenic action on ?-synuclein (?-syn) whose aggregation is associated to the pathogenesis of Parkinson's disease (PD). Most of these molecules act as promiscuous anti-amyloidogenic agents, interacting with the diverse amyloidogenic proteins (mostly unfolded) through non-specific hydrophobic interactions. Herein we investigated the effect of the vitamins K (phylloquinone, menaquinone and menadione), which are 1,4-naphthoquinone (1,4-NQ) derivatives, on ?-syn aggregation, comparing them with other anti-fibrillogenic molecules such as quinones, polyphenols and lipophilic vitamins. Vitamins K delayed ?-syn fibrillization in substoichiometric concentrations, leading to the formation of short, sheared fibrils and amorphous aggregates, which are less prone to produce leakage of synthetic vesicles. In seeding conditions, menadione and 1,4-NQ significantly inhibited fibrils elongation, which could be explained by their ability to destabilize preformed fibrils of ?-syn. Bidimensional NMR experiments indicate that a specific site at the N-terminal ?-syn (Gly31/Lys32) is involved in the interaction with vitamins K, which is corroborated by previous studies suggesting that Lys is a key residue in the interaction with quinones. Together, our data suggest that 1,4-NQ, recently showed up by our group as a potential scaffold for designing new monoamine oxidase inhibitors, is also capable to modulate ?-syn fibrillization in vitro. PMID:23064431

da Silva, Fernanda Luna; Coelho Cerqueira, Eduardo; de Freitas, Mônica Santos; Gonçalves, Daniela Leão; Costa, Lilian Terezinha; Follmer, Cristian

2013-01-01

339

Human Vitamin K 2,3-Epoxide Reductase Complex Subunit 1-like 1 (VKORC1L1) Mediates Vitamin K-dependent Intracellular Antioxidant Function*  

PubMed Central

Human vitamin K 2,3-epoxide reductase complex subunit 1-like 1 (VKORC1L1), expressed in HEK 293T cells and localized exclusively to membranes of the endoplasmic reticulum, was found to support both vitamin K 2,3-epoxide reductase (VKOR) and vitamin K reductase enzymatic activities. Michaelis-Menten kinetic parameters for dithiothreitol-driven VKOR activity were: Km (?m) = 4.15 (vitamin K1 epoxide) and 11.24 (vitamin K2 epoxide); Vmax (nmol·mg?1·hr?1) = 2.57 (vitamin K1 epoxide) and 13.46 (vitamin K2 epoxide). Oxidative stress induced by H2O2 applied to cultured cells up-regulated VKORC1L1 expression and VKOR activity. Cell viability under conditions of no induced oxidative stress was increased by the presence of vitamins K1 and K2 but not ubinquinone-10 and was specifically dependent on VKORC1L1 expression. Intracellular reactive oxygen species levels in cells treated with 2,3-dimethoxy-1,4-naphthoquinone were mitigated in a VKORC1L1 expression-dependent manner. Intracellular oxidative damage to membrane intrinsic proteins was inversely dependent on VKORC1L1 expression and the presence of vitamin K1. Taken together, our results suggest that VKORC1L1 is responsible for driving vitamin K-mediated intracellular antioxidation pathways critical to cell survival.

Westhofen, Philipp; Watzka, Matthias; Marinova, Milka; Hass, Moritz; Kirfel, Gregor; Muller, Jens; Bevans, Carville G.; Muller, Clemens R.; Oldenburg, Johannes

2011-01-01

340

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

341

Synthesis of 2,3-dihydronaphtho[2,3-d][1,3]thiazole-4,9-diones and 2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones and novel ring contraction and fusion reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] into 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones.  

PubMed

Treatment of N-substituted 2-(methylamino)naphthoquinones 3 and -anthracene-1,4-diones 4 with S2Cl2 and DABCO in chlorobenzene gave the corresponding 2,3-dihydronaphtho[2,3-d][1,3]thiazole-4,9-diones 1 and 2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones 2 by triethylamine addition, in high to moderate yields. The DABCO replacement for N-ethyldiisopropylamine in the reaction of anthracene-1,4-diones 4 led unexpectedly to the corresponding 2-thioxo-2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones 10. The reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] 1d, 2d with Et3N in chlorobenzene under reflux yielded 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones 15, 16, i.e., ring contraction and fusion products. A plausible mechanism was proposed for the formation of the products. PMID:23616798

Konstantinova, Lidia S; Lysov, Kirill A; Souvorova, Ljudmila I; Rakitin, Oleg A

2013-01-01

342

Chimaphilin induces apoptosis in human breast cancer MCF-7 cells through a ROS-mediated mitochondrial pathway.  

PubMed

Chimaphilin, 2,7-dimethyl-1,4-naphthoquinone, is extracted from pyrola [Passiflora incarnata Fisch.]. In this study, the anticancer activity and underlying mechanisms of chimaphilin toward human breast cancer MCF-7 cells are firstly investigated. Chimaphilin could inhibit the viability of MCF-7 cells in a concentration-dependent manner, and the IC50 value was 43.30?M for 24h. Chimaphilin markedly induced apoptosis through the investigation of characteristic apoptotic morphological changes, nuclear DNA fragmentation, annexin V-FITC/propidium iodide (PI) double staining. Flow cytometry assay revealed that chimaphilin triggered a significant generation of ROS and disruption of mitochondrial membrane potential. Additionally, western blotting assay showed that chimaphilin suppressed Bcl-2 level and enhanced Bad level, then activated caspase-9 and caspase-3, and further activated the poly ADP-ribose polymerase (PARP), finally induced cell apoptosis involving the mitochondrial pathway. Furthermore, free radical scavengers N-acetyl-L-cysteine (NAC) pretreatment test testified that chimaphilin could increase the generation of ROS, then induce cell apoptosis. In general, the present results demonstrated that chimaphilin induced apoptosis in human breast cancer MCF-7 cells via a ROS-mediated mitochondrial pathway. PMID:24793375

Ma, Wei-Dong; Zou, Yong-Peng; Wang, Peng; Yao, Xiao-Hui; Sun, Yao; Duan, Ming-Hui; Fu, Yu-Jie; Yu, Bo

2014-08-01

343

Piezoelectric pumping in flow analysis: Application to the spectrophotometric determination of gabapentin.  

PubMed

Solutions propelling devices are fundamental components of a flow-based analytical manifold. In this work different manifold configurations were implemented to evaluate the performance of multiple piezoelectric micro-pumps used as solutions insertion and propulsion devices. The micro-pumps are piezo-actuated micro-diaphragm pumps with passive check valves characterised by a small compact size and low power demands, and are able to produce reproducible flow rates of up to 4 mL min(-1). The flow rate is controlled by the frequency of the piezoelectric actuator (up to 20 Hz). As an additional feature, piezoelectric micro-pumps actuation generates a pulsed flowing stream that ensures a faster sample/reagent mixing contributing to improved reaction development. The developed flow approach was assessed in the spectrophotometric determination of gabapentin in pharmaceutical preparations upon reaction with 1,2-naphthoquinone-4-sulfonate in alkaline medium. Distinct flow manifold configurations were designed for achievement of different solutions management. Linear calibrations plots for gabapentin concentrations of up to 150 mg L(-1), with relative standard deviations of less than 1.50% (n=10) and a sample throughput of about 28 determinations per hour, were obtained. PMID:17903459

Ribeiro, Marta F T; Santos, João L M; Lima, José L F C

2007-09-26

344

Antimicrobial and antiinflammatory activities of extracts and constituents of Oroxylum indicum (L.) Vent.  

PubMed

Dichloromethane extracts of the stembark and root of Oroxylum indicum were found to have antimicrobial activities against Gram positive bacteria (Bacillus subtilis and Staphylococcus aureus), Gramnegative bacteria (Escherichia coli and Pseudomonas aeruginosa) and a yeast (Candida albicans). Bioassay-guided chromatographic fractionation led to the isolation of flavonoids (bacailein and chrysin) and a naphthoquinone, lapachol. Lapachol was found active against the Gram-positive bacteria, 5 ?g giving a zone of inhibition equivalent to that shown by 5 ?g streptomycin, whereas 5 ?g chrysin gave inhibition zones of equal size to 5 ?g streptomycin against Candida albicans and Pseudomonas aeruginosa. The inhibitory activity of lapachol from O. indicum root against soya 5-lipoxygenase (IC(50) 0.79 ?g/ml) was equivalent to that of the positive control fisetin (IC(50) 0.97 ?g/ml) and 50 ?g/ml of the dichloromethane extract of the rootbark gave 100% inhibition of leukocyte lipoxygenase. These activities might indicate an antiinflammatory effect for the dichloromethane extract, mainly due to the lapachol content. PMID:23195987

Mat Ali, R; Houghton, P J; Raman, A; Hoult, J R

1998-10-01

345

Fragmentation studies and electrospray ionization mass spectrometry of lapachol: protonated, deprotonated and cationized species.  

PubMed

Electrospray ionization mass spectrometric analysis of lapachol (2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone) was accomplished in order to elucidate the gas-phase dissociation reactions of this important biologically active natural product. The occurrence of protonated and cationized species in the positive mode and of deprotonated species in the negative mode was explored by means of collision-induced dissociation (CID) experiments. For the protonated molecule, the H(2)O and C(4)H(8) losses occur by two competitive channels. For the deprotonated molecule, the even-electron rule is not conserved, and the radicalar species are eliminated by formation of distonic anions. The fragmentation mechanism for each ion was suggested on the basis of computational thermochemistry. Atomic charges, relative energies, and frontier orbitals were employed aiming at a better understanding of the gas-phase reactivity of lapachol. Potential energy surfaces for fragmentation reactions were obtained by the B3LYP/6-31+G(d,p) model. PMID:20552691

Vessecchi, Ricardo; Emery, Flavio S; Galembeck, Sérgio E; Lopes, Norberto P

2010-07-30

346

Expression Patterns of Glutathione Transferase Gene (GstI) in Maize Seedlings Under Juglone-Induced Oxidative Stress  

PubMed Central

Juglone (5-hydroxy-1,4-naphthoquinone) has been identified in organs of many plant species within Juglandaceae family. This secondary metabolite is considered as a highly bioactive substance that functions as direct oxidant stimulating the production of reactive oxygen species (ROS) in acceptor plants. Glutathione transferases (GSTs, E.C.2.5.1.18) represent an important group of cytoprotective enzymes participating in detoxification of xenobiotics and limiting oxidative damages of cellular macromolecules. The purpose of this study was to investigate the impact of tested allelochemical on growth and development of maize (Zea mays L.) seedlings. Furthermore, the effect of juglone-induced oxidative stress on glutathione transferase (GstI) gene expression patterns in maize seedlings was recorded. It was revealed that 4-day juglone treatment significantly stimulated the transcriptional activity of GstI in maize seedlings compared to control plants. By contrast, at the 6th and 8th day of experiments the expression gene responses were slightly lower as compared with non-stressed seedlings. Additionally, the specific gene expression profiles, as well as the inhibition of primary roots and coleoptile elongation were proportional to juglone concentrations. In conclusion, the results provide strong molecular evidence that allelopathic influence of juglone on growth and development of maize seedlings may be relevant with an induction of oxidative stress in acceptor plants.

Sytykiewicz, Hubert

2011-01-01

347

Modulatory effects of Tabebuia impetiginosa (Lamiales, Bignoniaceae) on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster  

PubMed Central

The wing Somatic Mutation and Recombination Test (SMART) in D. melanogaster was used to study genotoxicity of the medicinal plant Tabebuia impetiginosa. Lapachol (naphthoquinone) and ?-lapachone (quinone) are the two main chemical constituents of T. impetiginosa. These compounds have several biological properties. They induce apoptosis by generating oxygen-reactive species, thereby inhibiting topoisomerases (I and II) or inducing other enzymes dependent on NAD(P)H:quinone oxidoreductase 1, thus affecting cell cycle checkpoints. The SMART was used in the standard (ST) version, which has normal levels of cytochrome P450 (CYP) enzymes, to check the direct action of this compound, and in the high bioactivation (HB) version, which has a high constitutive level of CYP enzymes, to check for indirect action in three different T. impetiginosa concentrations (10%, 20% or 40% w/w). It was observed that T. impetiginosa alone did not modify the spontaneous frequencies of mutant spots in either cross. The negative results observed prompted us to study this phytotherapeuticum in association with the reference mutagen doxorubicin (DXR). In co-treated series, T. impetiginosa was toxic in both crosses at higher concentration, whereas in the HB cross, it induced a considerable potentiating effect (from ~24.0 to ~95.0%) on DXR genotoxity. Therefore, further research is needed to determine the possible risks associated with the exposure of living organisms to this complex mixture.

2009-01-01

348

Mechanistic and structural basis for inhibition of thymidylate synthase ThyX  

PubMed Central

Nature has established two mechanistically and structurally unrelated families of thymidylate synthases that produce de novo thymidylate or dTMP, an essential DNA precursor. Representatives of the alternative flavin-dependent thymidylate synthase family, ThyX, are found in a large number of microbial genomes, but are absent in humans. We have exploited the nucleotide binding pocket of ThyX proteins to identify non-substrate-based tight-binding ThyX inhibitors that inhibited growth of genetically modified Escherichia coli cells dependent on thyX in a manner mimicking a genetic knockout of thymidylate synthase. We also solved the crystal structure of a viral ThyX bound to 2-hydroxy-3-(4-methoxybenzyl)-1,4-naphthoquinone at a resolution of 2.6 Å. This inhibitor was found to bind within the conserved active site of the tetrameric ThyX enzyme, at the interface of two monomers, partially overlapping with the dUMP binding pocket. Our studies provide new chemical tools for investigating the ThyX reaction mechanism and establish a novel mechanistic and structural basis for inhibition of thymidylate synthesis. As essential ThyX proteins are found e.g. in Mycobacterium tuberculosis and Helicobacter pylori, our studies have also potential to pave the way towards the development of new anti-microbial compounds.

Basta, Tamara; Boum, Yap; Briffotaux, Julien; Becker, Hubert F.; Lamarre-Jouenne, Isabelle; Lambry, Jean-Christophe; Skouloubris, Stephane; Liebl, Ursula; Graille, Marc; van Tilbeurgh, Herman; Myllykallio, Hannu

2012-01-01

349

Oxygen-Insensitive Nitroreductases NfsA and NfsB of Escherichia coli Function under Anaerobic Conditions as Lawsone-Dependent Azo Reductases  

PubMed Central

Quinones can function as redox mediators in the unspecific anaerobic reduction of azo compounds by various bacterial species. These quinones are enzymatically reduced by the bacteria and the resulting hydroquinones then reduce in a purely chemical redox reaction the azo compounds outside of the cells. Recently, it has been demonstrated that the addition of lawsone (2-hydroxy-1,4-naphthoquinone) to anaerobically incubated cells of Escherichia coli resulted in a pronounced increase in the reduction rates of different sulfonated and polymeric azo compounds. In the present study it was attempted to identify the enzyme system(s) responsible for the reduction of lawsone by E. coli and thus for the lawsone-dependent anaerobic azo reductase activity. An NADH-dependent lawsone reductase activity was found in the cytosolic fraction of the cells. The enzyme was purified by column chromatography and the amino-terminal amino acid sequence of the protein was determined. The sequence obtained was identical to the sequence of an oxygen-insensitive nitroreductase (NfsB) described earlier from this organism. Subsequent biochemical tests with the purified lawsone reductase activity confirmed that the lawsone reductase activity detected was identical with NfsB. In addition it was proven that also a second oxygen-insensitive nitroreductase of E. coli (NfsA) is able to reduce lawsone and thus to function under adequate conditions as quinone-dependent azo reductase.

Rau, Jorg; Stolz, Andreas

2003-01-01

350

The molecular mechanisms and gene expression profiling for shikonin-induced apoptotic and necroptotic cell death in U937 cells.  

PubMed

Shikonin (SHK), a natural naphthoquinone derived from the Chinese medical herb Lithospermum erythrorhizon, induces both apoptosis and necroptosis in several cancer cell lines. However, the detailed molecular mechanisms involved in the initiation of cell death are still unclear. In the present study, caspase-dependent apoptosis was induced by SHK treatment at 1?M after 6h in U937 cells, with increase in DNA fragmentation, generation of intracellular reactive oxygen species (ROS), fraction of cells with low mitochondrial membrane potential (MMP), and in the expression of BH3 only proteins Noxa and tBid. Interestingly, caspase-independent cell death was also detected with SHK treatment at 10?M, observed as increase in SYTOX® Green staining and release of lactate dehydrogenase (LDH). Necrostatin-1 (Nec-1) completely inhibited the SHK-induced leakage of LDH and SYTOX® Green staining. Cell permeable exogenous glutathione (GSH) completely inhibited 1?M SHK-induced apoptosis and converted 10?M SHK-induced necroptosis to apoptosis. Gene expression profiling revealed that 353 genes were found to be significantly regulated by 1?M and 85 genes by 10?M of SHK treatment, respectively. Among these genes, the transcription factor 3 (ATF3) and DNA-damage-inducible transcript 3 (DDIT3) were highly expressed at 1?M of SHK treatment, while tumor necrosis factor (TNF) expression mainly increased at 10?M treatment. These findings provide novel information for the molecular mechanism of SHK-induced apoptosis and necroptosis. PMID:23811387

Piao, Jin-Lan; Cui, Zheng-Guo; Furusawa, Yukihiro; Ahmed, Kanwal; Rehman, Mati Ur; Tabuchi, Yoshiaki; Kadowaki, Makoto; Kondo, Takashi

2013-09-25

351

A Novel Class of Small Molecule Inhibitors of HDAC6  

PubMed Central

Histone deacetylases (HDACs) are a family of enzymes that play significant roles in numerous biological processes and diseases. HDACs are best known for their repressive influence on gene transcription through histone deacetylation. Mapping of non-histone acetylated proteins and acetylation-modifying enzymes involved in various cellular pathways has shown protein acetylation/deacetylation also plays key roles in a variety of cellular processes including RNA splicing, nuclear transport, and cytoskeletal-remodeling. Studies of HDACs have accelerated due to the availability of small molecule HDAC inhibitors, most of which contain a canonical hydroxamic acid or benzamide that chelates the metal catalytic site. To increase the pool of unique and novel HDAC inhibitor pharmacophores, a pharmacological active compound screen was performed. Several unique HDAC inhibitor pharmacophores were identified in vitro. One class of novel HDAC inhibitors, with a central naphthoquinone structure, displayed a selective inhibition profile against HDAC6. Here we present the results of a unique class of HDAC6 inhibitors identified using this compound library screen. In addition, we demonstrated treatment of human acute myeloid leukemia cell line MV4-11 with the selective HDAC6 inhibitors decreases levels of mutant FLT-3 and constitutively active STAT5, and attenuates Erk phosphorylation, all of which are associated with the inhibitor’s selective toxicity against leukemia.

Inks, Elizabeth S.; Josey, Benjamin J.; Jesinkey, Sean R.; Chou, C. James

2011-01-01

352

Interaction of chlorinated phenolics and quinones with the mitochondrial respiration: a comparison of the o- and p-chlorinated quinones and hydroquinones  

SciTech Connect

Interest in the environmental toxicology of chlorinated catechols and their analogous quinones was prompted by their acute toxicity towards fish and other aquatic organisms. Chlorophenols, such as pentachlorophenol, as well as tetrachlorocatechol have been suggested to uncouple mitochondrial oxidative phosphorylation while chloranil and tetrachloro-o-benzoquinone have been shown to inhibit liver mitochondrial respiration, which may be related to their cytotoxicity. Another chlorinated quinone fungicide, 2,3 dichloro-1,4-naphthoquinone (CNQ) has been studied and shown to both uncouple oxidative phosphorylation and inhibit respiration in liver and heart mitochondria. CNQ was shown to undergo redox cycling with mitochondria, with a concomitant production of toxic oxygen species including superoxide and hydrogen peroxide. These reactive oxygen species were associated with the generation of mitochondrial oxidative stress, and were related to the toxic action of CNQ. Based upon these previous findings, the authors examined the interaction of both the ortho and para isomers of tetrachloro-benzoquinone and their corresponding hydroquinones with mitochondria in order to prove their mechanism of actions and compare the reactions of the various isomers.

Pritsos, C.A.; Pointon, M.; Pardini, R.S.

1987-05-01

353

Microplate analytical method for quinones by pulse photo-irradiation and chemiluminescence detection.  

PubMed

Quinones are widely distributed in nature and have various bioactivities. Besides, quinones are also considered as toxicological intermediates which cause severe dangerous effects. Hereby, a sensitive, simple, and rapid method is reported for quinones determination. The proposed method employed time resolved fluorescence (TRF) microplate reader based chemiluminescent (CL) detection for the first time as a novel approach for measurement. Under pulse photo-irradiation, the unique photochemical characteristic of quinones is exploited to liberate reactive oxygen species (ROS) which reacted with photosensitized CL reagent. L-012, luminol analogue, was selected for its high sensitivity. Under our investigation, para-quinones showed high CL response when compared to ortho-quinones. A linear response was obtained for studied quinone concentrations in the range of 0.05-50 ?M for 1,4-naphthquinone and of 0.05-150 ?M for 2-methyl-1,4-naphthoquinone (menadione) and 9,10-anthraquinone with detection limit (blank + 3SD) of 0.01 ?M. The proposed method allowed the rapid determination of large number of samples in very short time (96 sample/125 s). The proposed method was successfully applied for determination of menadione in spiked human serum. PMID:22910835

Elgawish, Mohamed Saleh; Shimomai, Chikako; Kishikawa, Naoya; Ohyama, Kaname; Nakashima, Kenichiro; Kuroda, Naotaka

2012-10-21

354

Enhanced Ca2+ entry, ceramide formation, and apoptotic death of erythrocytes triggered by plumbagin.  

PubMed

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, 1), a natural product from plants with potential anticancer potency, induces apoptosis. Mechanisms involved in 1-induced apoptosis include mitochondrial depolarization, inactivation of NF-?B, and altered expression of anti- and proapoptotic Bcl proteins. Similar to nucleated cells, erythrocytes may undergo suicidal death or eryptosis, which, like apoptosis, results in cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include increase of cytosolic Ca(2+) activity ([Ca(2+)]i) and ceramide formation. The present study explored whether 1 stimulates eryptosis. Cell volume was estimated from forward scatter, phosphatidylserine exposure from annexin-V-binding, hemolysis from hemoglobin release, [Ca(2+)]i from Fluo-3 fluorescence, and ceramide abundance utilizing antibodies. A 48 h exposure to 1 (2 ?M) decreased forward scatter and increased annexin-V-binding significantly, events paralleled by increased [Ca(2+)]i and ceramide formation. Exposure to 1 was followed by a slight but significant increase of hemolysis. Removal of extracellular Ca(2+) slightly, but significantly blunted the effect of 1 (2 ?M) on annexin-V-binding. The present observations demonstrate that 1 may trigger suicidal death of erythrocytes, cells devoid of mitochondria and nuclei. PMID:23110447

Lupescu, Adrian; Jilani, Kashif; Zbidah, Mohanad; Lang, Elisabeth; Lang, Florian

2012-11-26

355

CRM1 is a direct cellular target of the natural anti-cancer agent plumbagin.  

PubMed

Plumbagin, a naphthoquinone derived from the medicinal plant Plumbago zeylanica, has been shown to exert anti-cancer and anti-proliferative activities in vitro as well as in animal tumor models. However, the mechanism underlying its anti-tumor action still remains unclear. CRM1 is a nuclear export receptor involved in the active transport of tumor suppressors whose function is altered in cancer due to increased expression and overactive transport. We showed that CRM1 is a direct cellular target of plumbagin. The nuclei of cells incubated with plumbagin accumulated tumor-suppressor proteins and inhibited the interactions between CRM1 and these proteins. Particularly, we demonstrated that plumbagin could specifically react with the conserved Cys(528) of CRM1 but not with a Cys(528) mutant peptide through Mass spectrometric analysis. More importantly, cancer cells that are transfected with mutant CRM1 (C528S) are resistant to the inhibitory effects of plumbagin, demonstrating that the inhibition is through direct interaction with Cys(528) of CRM1. The inhibition of nuclear traffic by plumbagin may account for its therapeutic properties in cancer and inflammatory diseases. Our findings could contribute to the development of a new class of CRM1 inhibitors. PMID:24739265

Liu, Xuejiao; Niu, Mingshan; Xu, Xiaoyu; Cai, Wei; Zeng, Lingyu; Zhou, Xiuping; Yu, Rutong; Xu, Kailin

2014-01-01

356

Novel anti-cancer role of naphthazarin in human gastric cancer cells.  

PubMed

Gastric cancer is one of the most common malignant tumors and the second cause of cancer-related deaths worldwide. Naphthoquinones such as juglone and plumbagin are compounds used extensively to overcome resistance to chemotherapeutic agents in cancers due to their cytotoxic role. This study is the first to investigate the anti-cancer effect of naphthazarin (Naph), one of the naphthaquinones, in human gastric cancer AGS cells. We showed that Naph exhibited effective preferential cell growth inhibition via G2/M phase arrest and apoptosis, which was associated with reduced levels of Cdc2 and Cdc25C expression. Naph also increased cleaved caspase-3 and Poly ADR(adenosine diphosphate ribose) Polymerase expression, ?-H2AX expression (an indicator of DNA double strand breaks) and DNA fragmentation. We also found the generation of reactive oxygen species is a critical mediator in Naph-induced cell growth inhibition and apoptosis. The non-protein antioxidant, glutathione significantly abolished Naph-mediated inhibition of cell growth and apoptosis. Taken together, our findings showed that Naph not only inhibited cell growth, but also induced apoptosis of AGS cells, suggesting that Naph may be a potential candidate for cancer therapy against gastric cancers. PMID:21904775

Kim, Jin-Ah; Lee, Eun Kyeong; Park, Seong Joon; Kim, Nam Deuk; Hyun, Dong-Hoon; Lee, Chang Geun; Lee, Jae Ho; Yang, Kwang Mo; Heo, Kyu; Son, Tae Gen

2012-01-01

357

Interventional effects of plumbagin on experimental ulcerative colitis in mice.  

PubMed

Plumbagin (1) is a naphthoquinone constituent of plants that have been used in traditional systems of medicine since ancient times. In the present study, the role of 1 was examined on the amelioration of ulcerative colitis, an inflammatory bowel disease that is not curable currently. Plumbagin was tested at a dose of 6-10 mg/kg body weight in acute and chronic disease models. Diseased mice receiving 1 at 8-10 mg/kg demonstrated a significant suppression of disease symptoms in both models. However, body weight loss was not restored in either of the models. Levels of proinflammatory cytokines (TNF-?, IFN-?, and IL-17) were reduced significantly by 1 in mice suffering from chronic disease, while cytokine levels remained unaffected in mice with acute disease. However, the percentage of inflammatory (CD14+/CD16+) monocytes present in peripheral blood was significantly reduced by >3-fold (p < 0.05) in treatment groups relative to controls in the acute model. Histological evaluations exhibited the restoration of goblet cells, crypts, and the submucosa along with a significant reduction in monocyte aggregation in colon sections from mice receiving treatment with 1. Restoration in colon size was also observed in the treatment groups. PMID:23742275

Pile, Justin E; Navalta, James W; Davis, Cheryl D; Sharma, Nilesh C

2013-06-28

358

Comparative study of three Plumbago L. species (Plumbaginaceae) by microscopy, UPLC-UV and HPTLC.  

PubMed

This paper presents a comparative study of anatomy of leaves, stems and roots of three species of Plumbago, namely P. auriculata Lam., P. indica L. and P. zeylanica L. by light microscopy. The paper also provides qualitative and quantitative analysis of the naphthoquinone, plumbagin-a major constituent present in these species-using UPLC-UV. Microscopic examinations revealed the presence of distinctive differences in the anatomical features of the leaf, stem and root of the three species, and these can thus be used for identification and authentication of these species. UPLC-UV analysis showed the highest concentration of plumbagin in the roots of P. zeylanica (1.62% w/w) followed by the roots of P. indica (0.97% w/w) and then P. auriculata (0.33-0.53% w/w). In contrast, plumbagin was not detected in the stems and leaves of P. indica and in the leaves of P. auriculata, whereas very low concentrations (<0.02% w/w) of plumbagin were detected in the stems and leaves of P. zeylanica and in the stems of P. auriculata. HPTLC fingerprints of the leaf and root of the three species exhibited distinguishable profiles, while those of the stems were undifferentiated. PMID:23151906

Galal, Ahmed M; Raman, Vijayasankar; Avula, Bharathi; Wang, Yan-Hong; Rumalla, Chidananda Swamy; Weerasooriya, Aruna Dharmapriya; Khan, Ikhlas A

2013-07-01

359

Possible mechanism of superoxide formation through redox cycling of plumbagin in pig heart.  

PubMed

The purpose of this study is to elucidate the possible mechanism of superoxide formation through redox cycling of plumbagin (PLG) in pig heart. Of four 1,4-naphthoquinones tested in this study, PLG was most efficiently reduced in the cytosolic fraction of pig heart. On the other hand, lawsone (LAS) was little reduced. Thus, whether or not PLG and LAS induce the formation of superoxide anion radical in pig heart cytosol was examined, by using the methods of cytochrome c reduction and chemiluminescence. PLG significantly induced the formation of superoxide anion radical, even though LAS had no ability to mediate superoxide formation. PLG was a significant inhibitor for the stereoselective reduction of 4-benzoylpyridine (4-BP) catalyzed by tetrameric carbonyl reductase (TCBR) in pig heart cytosol. Furthermore, PLG was confirmed to competitively inhibit the 4-BP reduction, and the optimal pH for the PLG reduction was around 6.0 similar to that for the 4-BP reduction. These results suggest that PLG mediates superoxide formation through its redox cycling involved in the two-electron reduction catalyzed by TCBR, and induces oxidative stress in pig heart. PMID:22198053

Shimada, Hideaki; Yamaoka, Yusuke; Morita, Reiko; Mizuno, Takayuki; Gotoh, Kousei; Higuchi, Toshiyuki; Shiraishi, Takayuki; Imamura, Yorishige

2012-03-01

360

Mediators-assisted reductive biotransformation of tetrabromobisphenol-A by Shewanella sp. XB.  

PubMed

The anaerobic biotransformation of tetrabromobisphenol A (TBBPA) was mainly observed in the consortia so far. The role of redox mediators in anaerobic TBBPA biotransformation by Shewanella sp. distributed widely in environments was investigated for the first time. The results showed the flavins secretion of Shewanella sp. XB was highly dependent on initial TBBPA concentration. The corresponding first-order rate constants (k) of TBBPA transformation decreased to 0.007 d(-1) when TBBPA concentration increased up to 80 mg/L. Moreover, the removal rate of TBBPA (80 mg/L) was significantly enhanced in treatments amended with cyanocobalamin, riboflavin, 2-hydroxy-1,4-naphthoquinone and Aldrich humic acid with k values of 0.42, 0.19, 0.16, and 0.07 d(-1), respectively. In addition, some redox proteins were secreted and played a role in flavins-mediated extracellular biotransformation of TBBPA by Shewanella sp. XB. These findings are beneficial to better understand TBBPA fate in natural environments and to develop efficient biotreatment strategies of TBBPA pollutions. PMID:23735802

Wang, Jing; Fu, Zhenzhen; Liu, Guangfei; Guo, Ning; Lu, Hong; Zhan, Yaoyao

2013-08-01

361

Interaction of Keap1 modified by 2-tert-butyl-1,4-benzoquinone with GSH: evidence for S-transarylation.  

PubMed

2-tert-Butyl-1,4-benzoquinone (TBQ), an electrophilic metabolite of butylated hydroxyanisole (BHA), causes activation of Nrf2 together with S-arylation of its negative regulator Keap1 in RAW264.7 cells. In a previous study, we found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) covalently modified with 1,2-naphthoquinone (1,2-NQ) undergoes S-transarylation by GSH, resulting in a decline of the GAPDH-1,2-NQ adduct and formation of a 1,2-NQ-SG adduct ( Miura , T. et al. ( 2011 ) Chem. Res. Toxicol. 24 , 1836 -1844 ). In the present study, we explored the possibility of GSH-dependent S-transarylation of the Keap1-TBQ adduct. Pretreatment with l-buthionine-(S,R)-sulfoximine and N-acetylcysteine prior to TBQ exposure of HepG2 cells suggested that the Keap1-TBQ adduct appears to undergo GSH-mediated S-transarylation because the resulting alterations in the intracellular GSH concentration affected Nrf2 activation caused by TBQ. In support of this hypothesis, a cell-free study demonstrated that incubation of the Keap1-TBQ adduct with GSH results in the removal of TBQ from Keap1 with the production of mono- and di-GSH adducts of TB(H)Q. These results suggest that GSH plays a role in reversible covalent modification of TBQ derived from BHA to Keap1 through the formation of a C-S bond. PMID:23718696

Abiko, Yumi; Kumagai, Yoshito

2013-07-15

362

Selective arylation, alkenylation, and cyclization of dibromonaphthols, using visible light, via carbene intermediates.  

PubMed

The photoreactivity of several 3-substituted-1,6-dibromo-2-naphthols has been investigated in neat acetonitrile in the presence of diluted Et3N and in aqueous buffered acetonitrile (pH 8, phosphate buffered), using visible light (450 nm). Hydrobromic acid loss in the presence of the base, for the unsubstituted naphthol, or heterolytic C-Br cleavage directly from the naphtholates, for the more acid 3-substutited naphthols (R = COOCH3, CONH2, CONMe2), generates electrophilic carbene intermediates, which have been successfully trapped by molecular oxygen, pyrrole, acrylonitrile, ethyl vinyl ether, and allyltrimethylsilane. Product distribution analysis reveals three types of products arising from (i) arylation, (ii) alkenylation, and (iii) cyclization reactions. The generation and the reactivity of alpha-ketocarbene intermediates, as electrophilc diradicals, has been supported by laser flash photolysis, with the detection of both the carbene (lambda(max) 510 nm) and 1,2-naphthoquinone-O-oxide (R = CONMe2, lambda(max) 600 nm) in the presence of O2. PMID:19522477

Verga, Daniela; Doria, Filippo; Mella, Mariella; Freccero, Mauro

2009-08-01

363

Photoarylation/alkylation of bromonaphthols.  

PubMed

The photochemistry of 6-bromo-2-naphthols has been studied in acetonitrile, aqueous acetonitrile, and isopropyl alcohol in the absence and in the presence of triethylamine by product distribution analysis, laser flash photolysis (LFP), fluorescence, phosphorescence, electrochemical measurements, and DFT calculations. Hydrobromic acid loss in the presence of Et(3)N occurs from the triplet state of 6-bromo-2-naphthol, generating an electrophilic carbene intermediate, which has been successfully trapped by oxygen, allyltrimethylsilane, 2,3-dimethylbut-2-ene, pyrrole, acrylonitrile, 1,4-dimethoxybenzene, and also pyridine. The generation and the reactivity of a triplet carbene intermediate has been supported by LFP, with the detection of 2,6-naphthoquinone-O-oxide (530 < lambda < 650 nm) in the presence of O(2). The electrophilic diradical character of the carbene has been supported by DFT calculations, using the B3LYP, PBE0, and MPWB1K functionals, with the 6-31+G(d,p) basis set and PCM solvation model. PMID:19123847

Pretali, Luca; Doria, Filippo; Verga, Daniela; Profumo, Antonella; Freccero, Mauro

2009-02-01

364

Modulatory effects of Tabebuia impetiginosa (Lamiales, Bignoniaceae) on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster.  

PubMed

The wing Somatic Mutation and Recombination Test (SMART) in D. melanogaster was used to study genotoxicity of the medicinal plant Tabebuia impetiginosa. Lapachol (naphthoquinone) and ?-lapachone (quinone) are the two main chemical constituents of T. impetiginosa. These compounds have several biological properties. They induce apoptosis by generating oxygen-reactive species, thereby inhibiting topoisomerases (I and II) or inducing other enzymes dependent on NAD(P)H:quinone oxidoreductase 1, thus affecting cell cycle checkpoints. The SMART was used in the standard (ST) version, which has normal levels of cytochrome P450 (CYP) enzymes, to check the direct action of this compound, and in the high bioactivation (HB) version, which has a high constitutive level of CYP enzymes, to check for indirect action in three different T. impetiginosa concentrations (10%, 20% or 40% w/w). It was observed that T. impetiginosa alone did not modify the spontaneous frequencies of mutant spots in either cross. The negative results observed prompted us to study this phytotherapeuticum in association with the reference mutagen doxorubicin (DXR). In co-treated series, T. impetiginosa was toxic in both crosses at higher concentration, whereas in the HB cross, it induced a considerable potentiating effect (from ~24.0 to ~95.0%) on DXR genotoxity. Therefore, further research is needed to determine the possible risks associated with the exposure of living organisms to this complex mixture. PMID:21637695

de Sousa, Neila C; de Rezende, Alexandre A A; da Silva, Regildo M G; Guterres, Zaira R; Graf, Ulrich; Kerr, Warwick E; Spanó, Mário A

2009-04-01

365

Screening of Potential anti-Trypanosoma cruzi Candidates: In Vitro and In Vivo Studies  

PubMed Central

Chagas disease (CD), caused by the intracellular protozoan Trypanosoma cruzi, is a parasitic illness endemic in Latin America. In the centennial after CD discovery by Carlos Chagas (1909), although it still represents an important public health problem in these affected areas, the existing chemotherapy, based on benznidazole and nifurtimox (both introduced more than four decades ago), is far from being considered ideal due to substantial toxicity, variable effect on different parasite stocks and well-known poor activity on the chronic phase. CD is considered one of the major “neglected” diseases of the world, as commercial incentives are very limited to guarantee investments for developing and discovering novel drugs. In this context, our group has been pursuing, over the last years, the efficacy, selectivity, toxicity, cellular targets and mechanisms of action of new potential anti-T. cruzi candidates screened from an in-house compound library of different research groups in the area of medicinal chemistry. A brief review regarding these studies will be discussed, mainly related to the effect on T. cruzi of (i) diamidines and related compounds, (ii) natural naphthoquinone derivatives, and (iii) megazol derivatives.

Soeiro, Maria de Nazare C; de Castro, Solange Lisboa

2011-01-01

366

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

367

Plants of Haiti used as antifertility agents.  

PubMed

Haitian empirical medicine sprang from both European (16th to 19th century) and African (especially voodoo) traditional therapies. The use of medicinal herbs is highly developed. Our purpose was to list the plants held to be antifertility agents in the island. We identified about twenty species more or less currently used by the women as abortifacients or emmenagogues. The chemistry and active components of a few species are well-known. However, for most of them, some were partially studied, and no relation could be established between their chemical composition and their potential activities, and the rest are chemically unknown. We chemically screened extracts of Casearia ilicifolia, Eleutherine bulbosa, Rhoeo spathacea and Stemodia durantifolia, and identified flavonoids, triterpenes and sterols in the leaves of C. ilicifolia, and naphthoquinones, and a new anthraquinone, anthracene-9,10-dione-1,5-diol-4-methoxy-3-methyl-2-carboxylic acid methyl ester, in the bulbs of E, bulbosa. R. spathacea showed a stimulative activity on mouse uterus. Antifertility screening tests of C. ilicifolia and E. bulbosa showed activity in rats, but also probably toxicity. PMID:7109665

Weniger, B; Haag-Berrurier, M; Anton, R

1982-07-01

368

Addition of hydrogen sulfide to juglone.  

PubMed

Evidence of the addition of hydrogen sulfide to 5-hydroxy-1,4-naphthoquinone (juglone) in aqueous solution was obtained by nuclear magnetic resonance spectrometry (NMR), electron paramagnetic resonance spectrometry (EPR), UV-visible absorbance spectroscopy, and kinetic measurements. Although numerous addition reactions of thiolated alkane and aromatic compounds to quinones have been previously reported, this study indicates that inorganic forms of S(-II) act as nucleophiles and electrophiles in addition reactions to the alpha,beta-conjugated system of the quinone. The results obtained are consistent with competing Michael and radical addition reactions, with radical addition favored with increasing pH. The simplest structure that simulated the NMR spectrum was a sulfur molecule containing sulfur bonded between two juglone molecules at C-2 or C-3, while EPR measurements of aqueous reaction solutions indicated the presence of a stable semiquinone that contained a sulfur substituent at C-2 or C-3. Quinones are present in trace amounts in natural organic matter, and the addition of S(-II) has important implications with respect to transport and transformation of a variety of compounds that react with natural organic matter. PMID:12099462

Perlinger, J A; Kalluri, V M; Venkatapathy, R; Angst, W

2002-06-15

369

Effect of biogenic photochromic electron acceptors on chlorophyll fluorescence  

NASA Astrophysics Data System (ADS)

It is shown that the photophysical properties of chlorophyll a (Chl) depend on the nature and relative amounts of 2-methyl-1,4-naphthoquinone (MNQ) and nicotinamide adenine dinucleotide phosphate (NADP). Photoinduced charge separation occurs in aqueous ethanol solutions of Chl (1 × 10-5 M) and NADP (5 × 10-6-5 × 10-4 M), resulting in the dynamic quenching of Chl fluorescence. Coordination interaction between Chl and NADP is established at an NADP concentration of ?5 × 10-4 M. The nonlinear Stern-Volmer dependence in this range is due to the input from static quenching. It is shown that the quenching of Chl fluorescence in an MNQ solution at Chl and MNQ concentrations of 1 × 10-5 M and 6.7 × 10-5-1 × 10-4 M, respectively, is described by a linear dependence in the Stern-Volmer coordinates; no complex formation is observed for Chl and MNQ under these conditions, and electron transfer is of the dynamic type. Static or mixed-type energy transfer from MNQ to Chl dominates at elevated MNQ concentrations.

Lobanov, A. V.; Klimenko, I. V.; Nevrova, O. V.; Zhuravleva, T. S.

2014-05-01

370

Photochemistry of a photosynthetic reaction center immobilized in lipidic cubic phases  

SciTech Connect

Photosynthetic reaction centers, isolated and purified from the facultative phototrophic bacterium Chloroflexus aurantiacus, were immobilized in optically transparent lipidic cubic phases composed of 42% (w/w) 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine and 58% (w/w) water. The immobilized photosynthetic protein retains its native properties, as indicated by visible and circular dichroic spectra. The ground state visible spectrum of the immobilized reaction centers is very similar to the corresponding spectrum in aqueous solution, indicating that the protein pigments are not extracted into the lipidic regions of the cubic phase. The secondary structure of the protein is maintained in the immobilized state, as determined by far-UV circular dichroism spectroscopy in the 200- to 250-nm range. Moreover, immobilized reaction centers retain their photochemical activity: a reversible photo-oxidation of the primary electron donor (P) is seen upon continuous illumination. Furthermore, the entrapment of reaction centers does not affect the kinetics of charge recombination between the photo-oxidized primary donor (P{sup +}) and the photoreduced primary quinone acceptor, generated by a short flash of light. Reaction centers devoided of the secondary quinone acceptor can be easily reconstituted in cubic phases by means of their coimmobilization with 1,4-naphthoquinone.

Hochkoeppler, A.; Venturoli, G.; Zannoni, D. [Univ. of Bologna (Italy). Dept. of Biology; Landau, E.M.; Luisi, P.L. [ETH Zentrum, Zuerich (Switzerland). Inst. fuer Polymere; Feick, R. [Max-Planck Inst. fuer Biochemie, Martinsried (Germany)

1995-04-20

371

Extracellular signal-regulated kinase, receptor interacting protein, and reactive oxygen species regulate shikonin-induced autophagy in human hepatocellular carcinoma.  

PubMed

Shikonin, a naphthoquinone derived from the Chinese medicinal plant Lithospermum erythrorhizon, shows potential to be a cancer chemotherapeutic agent. Our previous data demonstrate that high doses (about 6?M) of shikonin induce apoptosis in human hepatocellular carcinoma (HCC) cells. Here, we discovered that a low dose of shikonin (2.5?M) and a short treatment time (12h) induced autophagy, as evidenced by the upregulation of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, the formation of acidic autophagic vacuoles (AVOs), and the punctate fluorescence pattern of GFP-LC3 protein. Next, we investigated the mechanism and found reactive oxygen species accumulation after shikonin treatment. The reactive oxygen species scavengers NAC and Tiron completely blocked autophagy. We further found activation of ERK by generation of reactive oxygen species and inhibition of RIP pathway, which are at least partially connected to shikonin-induced autophagy. Moreover, experiments in vivo revealed similar results: shikonin caused the accumulation of reactive oxygen species and phospho-ERK and thus induced autophagy in a tumor xenograft model. These findings suggest that shikonin is an inducer of autophagy and may be a promising clinical antitumor drug. PMID:24886888

Gong, Ke; Zhang, Zhenxing; Chen, Yicheng; Shu, Hong-Bing; Li, Wenhua

2014-09-01

372

CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts  

PubMed Central

Cytochrome P450 enzymes (CYPs) play major roles in generating highly functionalized terpenoids, but identifying the exact biotransformation step(s) catalyzed by plant CYP in terpenoid biosynthesis is extremely challenging. Tanshinones are abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components of the Chinese medicinal herb danshen (Salvia miltiorrhiza). Whereas the diterpene synthases responsible for the conversion of (E,E,E)-geranylgeranyl diphosphate into the abietane miltiradiene, a potential precursor to tanshinones, have been recently described, molecular characterization of further transformation of miltiradiene remains unavailable. Here we report stable-isotope labeling results that demonstrate the intermediacy of miltiradiene in tanshinone biosynthesis. We further use a next-generation sequencing approach to identify six candidate CYP genes being coregulated with the diterpene synthase genes in both the rhizome and danshen hairy roots, and demonstrate that one of these, CYP76AH1, catalyzes a unique four-electron oxidation cascade on miltiradiene to produce ferruginol both in vitro and in vivo. We then build upon the previous establishment of miltiradiene production in Saccharomyces cerevisiae, with incorporation of CYP76AH1 and phyto-CYP reductase genes leading to heterologous production of ferruginol at 10.5 mg/L. As ferruginol has been found in many plants including danshen, the results and the approaches that were described here provide a solid foundation to further elucidate the biosynthesis of tanshinones and related diterpenoids. Moreover, these results should facilitate the construction of microbial cell factories for the production of phytoterpenoids.

Guo, Juan; Zhou, Yongjin J.; Hillwig, Matthew L.; Shen, Ye; Yang, Lei; Wang, Yajun; Zhang, Xianan; Liu, Wujun; Peters, Reuben J.; Chen, Xiaoya; Zhao, Zongbao K.; Huang, Luqi

2013-01-01

373

Determination of organic acids by high-performance liquid chromatography with electrochemical detection during wine brewing.  

PubMed

Voltammetric determination of acids by means of the electrochemical reduction of quinone was applied to high-performance liquid chromatography (HPLC) with electrochemical detection (ED) for determining organic acids in fruit wines. A two-channel HPLC-ED system was fabricated by use of an ion-exclusion column and an electrochemical detector with a glassy carbon working electrode. Aqueous solution of 0.1 mM HClO(4) and ethanol containing 2-methyl-1,4-naphthoquinone served as a mobile phase and reagent solution, respectively. Determination of acetic, citric, lactic, malic, succinic, and tartaric acids was made by measuring the peak areas of the flow signals due to the reduction current of quinone caused by the eluted acids. The peak area was found to be linearly related to the acid amount ranging from 0.1 to 40 nmol per 20 microL injection. The present method was characterized by reproducibility with the simple and rapid procedure without derivatization of analytes. The method was shown as an effective means for following acid contents in fruit juices during fermentation with wine yeast. PMID:15030193

Kotani, Akira; Miyaguchi, Yuji; Tomita, Eiji; Takamura, Kiyoko; Kusu, Fumiyo

2004-03-24

374

Structure-activity relationships and colorimetric properties of specific probes for the putative cancer biomarker human arylamine N-acetyltransferase 1.  

PubMed

A naphthoquinone inhibitor of human arylamine N-acetyltransferase 1 (hNAT1), a potential cancer biomarker and therapeutic target, has been reported which undergoes a distinctive concomitant color change from red to blue upon binding to the enzyme. Here we describe the use of in silico modeling alongside structure-activity relationship studies to advance the hit compound towards a potential probe to quantify hNAT1 levels in tissues. Derivatives with both a fifty-fold higher potency against hNAT1 and a two-fold greater absorption coefficient compared to the initial hit have been synthesized; these compounds retain specificity for hNAT1 and its murine homologue mNat2 over the isoenzyme hNAT2. A relationship between pKa, inhibitor potency and colorimetric properties has also been uncovered. The high potency of representative examples against hNAT1 in ZR-75-1 cell extracts also paves the way for the development of inhibitors with improved intrinsic sensitivity which could enable detection of hNAT1 in tissue samples and potentially act as tools for elucidating the unknown role hNAT1 plays in ER+ breast cancer; this could in turn lead to a therapeutic use for such inhibitors. PMID:24758871

Egleton, James E; Thinnes, Cyrille C; Seden, Peter T; Laurieri, Nicola; Lee, Siu Po; Hadavizadeh, Kate S; Measures, Angelina R; Jones, Alan M; Thompson, Sam; Varney, Amy; Wynne, Graham M; Ryan, Ali; Sim, Edith; Russell, Angela J

2014-06-01

375

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.

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

2010-01-01

376

Analysis of atmospheric concentrations of quinones and polycyclic aromatic hydrocarbons in vapour and particulate phases  

NASA Astrophysics Data System (ADS)

Polycyclic aromatic hydrocarbons (PAH) are often measured in studies of atmospheric chemistry or health effects of air pollution, due to their known human carcinogenicity. In recent years, PAH quinone derivatives have also become a focus of interest, primarily because they can contribute to oxidative stress. This work reports concentrations of 17 PAH and 15 quinones measured in air samples collected at a trafficked roadside. Data are presented for four compounds not previously reported in ambient air: 2-methyl-1,4-naphthoquinone, 2,6-di-tert-butyl-1,4-benzoquinone, methyl-1,4-benzoquinone and 2,3-dimethylanthraquinone, and a large vapour phase component is measured, not analysed in most earlier studies. Analyses are reported also for SRM 1649a and 1649b, including many compounds (8 for SRM 1649a and 12 for SRM 1649b) for which concentrations have not previously been reported. This work assesses the vapour/particle phase distribution of PAHs and quinones in relation to their molecular weight, vapour pressure, polarity and Henry's Law constant, finding that both molecular weight and vapour pressure (which are correlated) are good predictors of the partitioning.

Delgado-Saborit, Juana Maria; Alam, Mohammed S.; Godri Pollitt, Krystal J.; Stark, Christopher; Harrison, Roy M.

2013-10-01

377

Electron shuttling across the interface of CdSe nanoparticles monitored by femtosecond laser spectroscopy  

SciTech Connect

The formation and decay of the optical hole (bleach) for 4 nm CdSe nanoparticles (NPs) with adsorbed electron acceptors (1,4-benzoquinone and 1,2-naphthoquinone) and the rise and decay of the reduced electron acceptors formed after interfacial electron transfer from the CdSe NPs were investigated by femtosecond laser spectroscopy. The ultrashort (200--400 fs) rise times of the bleach at the band-gap energy of the CdSe NP as well as of the acceptor radical anion are found to increase with increasing the excitation energy. This suggests that the electron transfer from the CdSe NP to the quinone electron acceptor occurs after thermalization of the excited hot electrons. The decay times of the transient absorption for the electron acceptor radical anions are found to be comparable to that of the CdSe NP bleach recovery time (3 ps). This suggests that the surface quinones shuttle the electron from the conduction band to the valence band of the excited NP. The authors contrast this behavior with the excited-state dynamics of the recently investigated CdS-MV{sup 2+} system in which the electron acceptor does not shuttle the accepted electron back to the hole in CdS.

Burda, C.; Green, T.C.; Link, S.; El-Sayed, M.A. [Georgia Inst. of Tech., Atlanta, GA (United States). Laser Dynamics Lab.] [Georgia Inst. of Tech., Atlanta, GA (United States). Laser Dynamics Lab.

1999-03-18

378

Biological evaluation of hydroxynaphthoquinones as anti-malarials  

PubMed Central

Background The hydroxynaphthoquinones have been extensively investigated over the past 50 years for their anti-malarial activity. One member of this class, atovaquone, is combined with proguanil in Malarone®, an important drug for the treatment and prevention of malaria. Methods Anti-malarial activity was assessed in vitro for a series of 3-alkyl-2-hydroxy-1,4-naphthoquinones (N1-N5) evaluating the parasitaemia after 48 hours of incubation. Potential cytotoxicity in HEK293T cells was assessed using the MTT assay. Changes in mitochondrial membrane potential of Plasmodium were measured using the fluorescent dye Mitrotracker Red CMXROS. Results Four compounds demonstrated IC50s in the mid-micromolar range, and the most active compound, N3, had an IC50 of 443 nM. N3 disrupted mitochondrial membrane potential, and after 1 hour presented an IC50??mit of 16 ?M. In an in vitro cytotoxicity assay using HEK 293T cells N3 demonstrated no cytotoxicity at concentrations up to 16 ?M. Conclusions N3 was a potent inhibitor of mitochondrial electron transport, had nanomolar activity against cultured Plasmodium falciparum and showed minimal cytotoxicity. N3 may serve as a starting point for the design of new hydroxynaphthoquinone anti-malarials.

2013-01-01

379

Menaquinone Analogs Inhibit Growth of Bacterial Pathogens  

PubMed Central

Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, and Streptococcus agalactiae at concentrations of 10 to 200 ?g/ml. Coenzyme Q1 reduced the ability of S. aureus to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit S. aureus growth. The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic reactive oxygen species and affect bacterial plasma membranes and biosynthetic machinery to interfere with two-component systems, respiration, and macromolecular synthesis. These compounds represent a novel class of potential topical therapeutic agents.

Merriman, Joseph A.; Salgado-Pabon, Wilmara; Mueller, Elizabeth A.; Spaulding, Adam R.; Vu, Bao G.; Chuang-Smith, Olivia N.; Kohler, Petra L.; Kirby, John R.

2013-01-01

380

Shikonin inhibits the growth of human prostate cancer cells via modulation of the androgen receptor  

PubMed Central

Shikonin, a natural naphthoquinone isolated from the traditional Chinese medicine Zi Cao (gromwell), has been shown to possess tumor cell killing activity. The human androgen receptor (AR) is a nuclear transcription factor that serves as a major therapeutic target for prostate cancer. However, AR regulation by shikonin has not been reported. We investigated the effects of shikonin on the growth of prostate cancer cells. We observed that shikonin decreased the expression of AR at both the mRNA and the protein levels in LNCaP and 22RV1 human prostate cancer cells. The results from a luciferase assay showed that shikonin decreased the transcriptional activity of AR. Moreover, shikonin treatment inhibited AR target gene expression, PSA and growth inhibition of prostate cancer cells. In conclusion, the present study shows for the first time that shikonin treatment causes transcriptional repression of AR and inhibition of its nuclear localization in human prostate cancer cells. We propose that shikonin, an anticancer drug extracted from natural sources, induces inhibition of cell growth through modulation of AR in androgen-responsive prostate cancer cells and is a candidate for use in cancer chemotherapy for human prostate cancer.

JANG, SOON YOUNG; JANG, EUN HYANG; JEONG, SEO YOUNG; KIM, JONG-HO

2014-01-01

381

Oxidative stress induction by (+)-cordiaquinone J triggers both mitochondria-dependent apoptosis and necrosis in leukemia cells.  

PubMed

(+)-Cordiaquinone J is a 1,4-naphthoquinone isolated from the roots of Cordia leucocephala that has antifungal and larvicidal effects. However, the cytotoxic effects of (+)-cordiaquinone J have never being explored. In the present study, the effect of (+)-cordiaquinone J on tumor cells viability was investigated, showing IC(50) values in the range of 2.7-6.6muM in HL-60 and SF-295 cells, respectively. Studies performed in HL-60 leukemia cells indicated that (+)-cordiaquinone J (1.5 and 3.0muM) reduces cell viability and 5-bromo-2-deoxyuridine incorporation after 24h of incubation. (+)-Cordiaquinone J showed rapid induction of apoptosis, as indicated by phosphatidylserine externalization, caspase activation, DNA fragmentation, morphologic changes, and rapid induction of necrosis, as indicated by the loss of membrane integrity and morphologic changes. (+)-Cordiaquinone J altered the redox potential of cells by inducing the depletion of reduced GSH intracellular content, the generation of reactive oxygen species and the loss of mitochondrial membrane potential. However, pre-treatment of cells with N-acetyl-l-cysteine abolished most of the observed effects related to (+)-cordiaquinone J treatment, including those involving apoptosis and necrosis induction. PMID:19962971

Marinho-Filho, José Delano B; Bezerra, Daniel P; Araújo, Ana J; Montenegro, Raquel C; Pessoa, Claudia; Diniz, Jaécio C; Viana, Francisco A; Pessoa, Otília D L; Silveira, Edilberto R; de Moraes, Manoel O; Costa-Lotufo, Letícia V

2010-02-12

382

Identification of transcriptome profiles and signaling pathways for the allelochemical juglone in rice roots.  

PubMed

Juglone (5-hydroxy-1,4-naphthoquinone) is known allelochemical, but its molecular mode of action is not well understood. We found that juglone induced reactive oxygen species production and calcium accumulation. To gain more insight into these cellular responses, we performed large-scale analysis of the rice transcriptome during juglone stress. Exposure to juglone triggered changes in transcript levels of genes related to cell growth, cell wall formation, chemical detoxification, abiotic stress response and epigenesis. The most predominant transcription-factor families were AP2/ERF, HSF, NAC, C2H2, WRKY, MYB and GRAS. Gene expression profiling of juglone-treated rice roots revealed upregulated signaling and biosynthesis of abscisic acid and jasmonic acid and inactivation of gibberellic acid. In addition, juglone upregulated the expression of two calcium-dependent protein kinases (CDPKs), 6 mitogen-activated protein kinase (MAPK) genes and 1 MAPK gene and markedly increased the activities of a CDPK-like kinase and MAPKs. Further characterization of these juglone-responsive genes may be helpful for better understanding the mechanisms of allelochemical tolerance in plants. PMID:22065257

Chi, Wen-Chang; Fu, Shih-Feng; Huang, Tsai-Lien; Chen, Yun-An; Chen, Chi-Cien; Huang, Hao-Jen

2011-12-01

383

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

384

Vitamin K 3 family members - Part II: Single crystal X-ray structures, temperature-induced packing polymorphism, magneto-structural correlations and probable anti-oncogenic candidature  

NASA Astrophysics Data System (ADS)

Temperature-induced packing polymorphism is observed for vitamin K 3 (menadione, 3-methyl-1,4-naphthoquinone, 1). Form 1a crystallizes at 300 K and 1b at 277 K both in the same space group P2 1/ c. Form 1b contains one molecule per asymmetric unit, performing anisotropy in g-factor viz. g z = 2.0082, g y = 2.0055 and g x = 2.0025, whereas form 1a contains two molecules in its asymmetric unit. Vitamin K 3 family members 2, [2-hydroxy vitamin K 3] and 3, [2-hydroxy-1-oximino vitamin K 3] also perform intrinsic neutral active naphthosemiquinone valence tautomers even in dark having spin concentrations due to hydrogen bonding and aromatic stacking interactions which are compared to vitamin K 3. The significant lateral C-H⋯O and O-H⋯? bifurcated or ?-? ? interactions are discussed for molecular associations and radical formations. X-ray structure of 3 revealed ?-? ? stack dimers as radicals signatured in EPR as triplet with five hyperfine splits [ ?( 14N) = 11.9 G]. The centrosymmetric biradicals in 3 show diamagnetism at high temperature but below 10 K it shows paramagnetism with ?eff as 0.19 B.M. Vitamin K 3 and its family members inhibit biological activities of acid phosphatase ( APase), which are proportional to their spin concentrations. This may relate to their probable anti-oncogenic candidature in future.

Rane, Sandhya; Ahmed, Khursheed; Salunke-Gawali, Sunita; Zaware, Santosh B.; Srinivas, D.; Gonnade, Rajesh; Bhadbhade, Mohan

2008-12-01

385

Development of Redox-Switchable Resorcin[4]arene Cavitands.  

PubMed

Conspectus Within the framework of miniaturization of electromechanical devices, the development of a redox-switchable molecular gripper as a tool for nanorobotics is appealing both from an academic and from a practical perspective. Such a tool should be able to controllably grab a molecular cargo, translocate it over considerable distances and time scales, and release it. Resorcin[4]arene cavitands seem to be an ideal platform for the development of molecular grippers due to their ability to adopt two spatially well-defined conformations: an expanded kite and a contracted vase. Furthermore, they possess "legs" for functionalization and attachment to metal surfaces. While changes in temperature, pH, and metal-ion concentration were known to induce conformational switching, redox-switchable cavitands remained a challenge. In this Account, we describe our efforts toward the development of a new class of resorcin[4]arene cavitands that are redox-switchable. First, we introduced the naphthoquinone moiety as a redox-active wall component and showed that cavitands containing four quinone walls strongly prefer the open kite conformation in both the quinone and hydroquinone redox states, while cavitands that contain two quinone and two quinoxaline walls can adopt both the vase and the kite conformations depending on solvent but not on redox state. Next, in order to introduce a driving force for the conformational switching process in diquinone cavitands, we designed cavitands with hydrogen bond acceptor groups on the quinoxaline walls. These acceptors were sought to establish hydrogen bonds with the hydroquinone groups in the reduced redox state, thereby stabilizing the vase form. Oxidation to the quinone state would remove these interactions, switching the cavitand back to the kite form. Cavitands equipped with different hydrogen bond acceptor groups were synthesized and evaluated. We found that carboxamide moieties are best suited to assist redox-induced switching of conformational and binding properties. With the goal of further increasing association constants and reducing guest-exchange rates via steric congestion, we exchanged the naphthoquinone with the triptycene-quinone moiety. The congesting influence of the triptycene-quinone moiety on the binding properties was quantified both in the presence and in the absence of additional hydrogen bond interactions that stabilize the vase form. X-ray crystallographic studies provided insights into the solid-state structures of the cavitands in different solvents and redox states. A significant enhancement of association constants and reduction in guest release rates was observed in the reduced redox state compared with the top-open system, yielding redox-switchable cavitand baskets. These studies represent a step towards the development of redox-switchable molecular grippers on metal surfaces. Future challenges will consist in the development of cavitands that will no longer rely on an external proton source for the switching process, allowing redox-switching to be performed in purely aprotic media. Finally, suitable leg functionalization would enable the grippers to be interfaced with metal surfaces. PMID:24814219

Pochorovski, Igor; Diederich, François

2014-07-15

386

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 agaisnt the Gram-positive bacteria Bacillus subtilis, Sarcinia lutea, and Staphyllococcus 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 15µg/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. Maximu

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

2014-07-01

387

Reactive Oxygen Species Prevent Imiquimod-Induced Psoriatic Dermatitis through Enhancing Regulatory T Cell Function  

PubMed Central

Psoriasis is a chronic inflammatory skin disease resulting from immune dysregulation. Regulatory T cells (Tregs) are important in the prevention of psoriasis. Traditionally, reactive oxygen species (ROS) are known to be implicated in the progression of inflammatory diseases, including psoriasis, but many recent studies suggested the protective role of ROS in immune-mediated diseases. In particular, severe cases of psoriasis vulgaris have been reported to be successfully treated by hyperbaric oxygen therapy (HBOT), which raises tissue level of ROS. Also it was reported that Treg function was closely associated with ROS level. However, it has been only investigated in lowered levels of ROS so far. Thus, in this study, to clarify the relationship between ROS level and Treg function, as well as their role in the pathogenesis of psoriasis, we investigated imiquimod-induced psoriatic dermatitis (PD) in association with Treg function both in elevated and lowered levels of ROS by using knockout mice, such as glutathione peroxidase-1?/? and neutrophil cytosolic factor-1?/? mice, as well as by using HBOT or chemicals, such as 2,3-dimethoxy-1,4-naphthoquinone and N-acetylcysteine. The results consistently showed Tregs were hyperfunctional in elevated levels of ROS, whereas hypofunctional in lowered levels of ROS. In addition, imiquimod-induced PD was attenuated in elevated levels of ROS, whereas aggravated in lowered levels of ROS. For the molecular mechanism that may link ROS level and Treg function, we investigated the expression of an immunoregulatory enzyme, indoleamine 2,3-dioxygenase (IDO) which is induced by ROS, in PD lesions. Taken together, it was implied that appropriately elevated levels of ROS might prevent psoriasis through enhancing IDO expression and Treg function.

Choi, Eun-Jeong; Hong, Min-Pyo; Kie, Jeong-Hae; Lim, Woosung; Lee, Hyeon Kook; Moon, Byung-In; Seoh, Ju-Young

2014-01-01

388

Induction of apoptosis by plumbagin through reactive oxygen species-mediated inhibition of topoisomerase II.  

PubMed

Reactive oxygen species (ROS) have been recognized as key molecules, which can selectively modify proteins and therefore regulate cellular signalling including apoptosis. Plumbagin, a naphthoquinone exhibiting antitumor activity, is known to generate ROS and has been found to inhibit the activity of topoisomerase II (Topo II) through the stabilization of the Topo II-DNA cleavable complex. The objective of this research was to clarify the role of ROS and Topo II inhibition in the induction of apoptosis mediated by plumbagin. As determined by the comet assay, plumbagin induced DNA cleavage in HL-60 cells, whereas in a cell line with reduced Topo II activity-HL-60/MX2, the level of DNA damage was significantly decreased. The onset of DNA strand break formation in HL-60 cells was delayed in comparison with the generation of intracellular ROS. In HL-60/MX2 cells, ROS were generated at a similar rate, whereas a significant reduction in the level of DNA damage was detected. The pretreatment of cells with N-acetylcysteine (NAC) attenuated plumbagin-induced DNA damage, pointing out to the involvement of ROS generation in cleavable complex formation. These results suggest that plumbagin-induced ROS does not directly damage DNA but requires the involvement of Topo II. Furthermore, experiments carried out using light spectroscopy indicated no direct interactions between plumbagin and DNA. The induction of apoptosis was significantly delayed in HL-60/MX2 cells indicating the involvement of Topo II inhibition in plumbagin-mediated apoptosis. Thus, these findings strongly suggest ROS-mediated inhibition of Topo II as an important mechanism contributing to the apoptosis-inducing properties of plumbagin. PMID:17618663

Kawiak, Anna; Piosik, Jacek; Stasilojc, Grzegorz; Gwizdek-Wisniewska, Anna; Marczak, Lukasz; Stobiecki, Maciej; Bigda, Jacek; Lojkowska, Ewa

2007-09-15

389

Anti-inflammatory and analgesic effect of plumbagin through inhibition of nuclear factor-?B activation.  

PubMed

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) (PL) is a naturally occurring yellow pigment found in the plants of the Plumbaginaceae, Droseraceae, Ancistrocladaceae, and Dioncophyllaceae families. It has been reported that PL exhibits anticarcinogenic, anti-inflammatory, and analgesic activities. However, the mechanism underlying its anti-inflammatory action remains unknown. In the current study, we investigated and characterized the anti-inflammatory and analgesic effects of PL orally administrated in a range of dosages from 5 to 20 mg/kg. We also examined the role of nuclear factor ?B (NF-?B) and proinflammatory cytokines and mediators in this effect. The results showed that PL significantly and dose-dependently suppressed the paw edema of rats induced by carrageenan and various proinflammatory mediators, including histamine, serotonin, bradykinin, and prostaglandin E(2). PL reduced the number of writhing episodes of mice induced by the intraperitoneal injection of acetic acid, but it did not reduce the writhing episode numbers induced by MgSO(4) in mice or prolong the tail-flick reaction time of rats to noxious thermal pain. Mechanistic studies showed that PL effectively decreased the production of the proinflammatory cytokines interleukin 1?, interleukin 6, and tumor necrosis factor ?. It also inhibited the expression of the proinflammatory mediators inducible nitric-oxide synthase and cyclooxygenase 2, whereas it did not inhibit the expression of cyclooxygenase 1. Further studies demonstrated that PL suppressed inhibitor of ?B? phosphorylation and degradation, thus inhibiting the phosphorylation of the p65 subunit of NF-?B. This study suggests that PL has a potential to be developed into an anti-inflammatory agent for treating inflammatory diseases. PMID:20858709

Luo, Pei; Wong, Yuen Fan; Ge, Lin; Zhang, Zhi Feng; Liu, Yuan; Liu, Liang; Zhou, Hua

2010-12-01

390

Plumbagin, Vitamin K3 Analogue, Suppresses STAT3 Activation Pathway through Induction of Protein Tyrosine Phosphatase, SHP-1: Potential Role in Chemosensitization  

PubMed Central

The activation of STAT3 has been linked with carcinogenesis through survival, proliferation, and angiogenesis of tumor cells. Agents that can suppress STAT3 activation have potential not only for prevention but also for treatment of cancer. In the present report, we investigated whether plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), an analogue of Vitamin K and isolated from chitrak (Plumbago zeylanica), an Ayurvedic medicinal plant, can modulate the STAT3 pathway. We found that plumbagin inhibited both constitutive and IL-6-inducible STAT3 phosphorylation in multiple myeloma (MM) cells and this correlated with the inhibition of c-Src, JAK1, and JAK2 activation. Vanadate, however, reversed the plumbagin-induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that plumbagin induced the expression of the protein tyrosine phosphatase, SHP-1; and silencing of the SHP-1 abolished the effect of plumbagin. This agent also downregulated the expression of STAT3-regulated cyclin D1, Bcl-xL, and VEGF, activated caspase-3, induced PARP cleavage, and increased the sub-G1 population of MM cells. Consistent with these results, overexpression of constitutive active STAT3 significantly reduced the plumbagin-induced apoptosis. When compared with AG490, a rationally designed STAT3/JAK2 inhibitor, plumbagin was found more potent in suppressing proliferation of cells. Plumbagin also significantly potentiated the apoptotic effects of thalidomide and bortezomib in MM cells. Overall, these results suggest that the plumbagin inhibits STAT3 activation pathway through induction of SHP-1 and this may mediate sensitization of STAT3 overexpressing cancers to chemotherapeutic agents.

Sandur, Santosh K.; Pandey, Manoj K; Sung, Bokyung; Aggarwal, Bharat B.

2009-01-01

391

Accelerated removal of Sudan dye by Shewanella oneidensis MR-1 in the presence of quinones and humic acids.  

PubMed

Although there have been many studies on bacterial removal of soluble azo dyes, much less information is available for biological treatment of water-insoluble azo dyes. The few bacterial species capable of removing Sudan dye generally require a long time to remove low concentrations of insoluble dye particles. The present work examined the efficient removal of Sudan I by Shewanella oneidensis MR-1 in the presence of redox mediator. It was found that the microbially reduced anthraquinone-2,6-disulfonate (AQDS) could abiotically reduce Sudan I, indicating the feasibility of microbially-mediated reduction. The addition of 100 ?M AQDS and other different quinone compounds led to 4.3-54.7 % increase in removal efficiencies in 22 h. However, adding 5-hydroxy-1,4-naphthoquinone into the system inhibited Sudan I removal. The presence of 10, 50 and 100 ?M AQDS stimulated the removal efficiency in 10 h from 26.4 to 42.8, 54.9 and 64.0 %, respectively. The presence of 300 ?M AQDS resulted in an eightfold increase in initial removal rate from 0.19 to 1.52 mg h?¹ g?¹ cell biomass. A linear relationship was observed between the initial removal rates and AQDS concentrations (0-100 ?M). Comparison of Michaelis-Menten kinetic constants revealed the advantage of AQDS-mediated removal over direct reduction. Different species of humic acid could also stimulate the removal of Sudan I. Scanning electronic microscopy analysis confirmed the accelerated removal performance in the presence of AQDS. These results provide a potential method for the efficient removal of insoluble Sudan dye. PMID:23539152

Liu, Guangfei; Zhou, Jiti; Ji, Qiuyan; Wang, Jing; Jin, Ruofei; Lv, Hong

2013-09-01

392

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.

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

393

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

394

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).

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

2012-01-01

395

Oxidative stress increases eukaryotic initiation factor 4E phosphorylation in vascular cells.  

PubMed Central

Dysregulated cell growth can be caused by increased activity of protein synthesis eukaryotic initiation factor (eIF) 4E. Dysregulated cell growth is also characteristic of atherosclerosis. It is postulated that exposure of vascular cells, such as endothelial cells, smooth muscle cells and monocytes/macrophages, to oxidants, such as oxidized low-density lipoprotein (oxLDL), leads to the elaboration of growth factors and cytokines, which in turn results in smooth muscle cell hyperproliferation. To investigate whether activation of eIF4E might play a role in this hyperproliferative response, vascular cells were treated with oxLDL, oxidized lipid components of oxLDL and several model oxidants, including H(2)O(2) and dimethyl naphthoquinone. Exposure to each of these compounds led to a dose- and time-dependent increase in eIF4E phosphorylation in all three types of vascular cells, correlated with a modest increase in overall translation rate. No changes in eIF4EBP, eIF2 or eIF4B modification state were observed. Increased eIF4E phosphorylation was paralleled by increased presence of eIF4E in high-molecular-mass protein complexes characteristic of its most active form. Anti-oxidants at concentrations typically employed to block oxidant-induced cell signalling likewise promoted eIF4E phosphorylation. The results of this study indicate that increased eIF4E activity may contribute to the pathophysiological events in early atherogenesis by increasing the expression of translationally inefficient mRNAs encoding growth-promoting proteins.

Duncan, Roger F; Peterson, Hazel; Hagedorn, Curt H; Sevanian, Alex

2003-01-01

396

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

397

Plasticity of the quinone-binding site of the complex II homolog quinol:fumarate reductase.  

PubMed

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

2013-08-23

398

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.

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

2012-01-01

399

Isolation and characterization of photosynthetic reaction centers from Rhodopseudomonas capsulata and Rhodopseudomonas sphaeroides  

SciTech Connect

Reaction centers were isolated by affinity chromatography on equine cytochrome C. Peripheral proteins were removed with 0.05% LDAO. Absorption and EPR spectra and bleaching assays indicate that the reaction centers retained their electron donors and acceptors in the native environment. Three reaction center polypeptides were isolated and submitted for amino-terminal sequence determination. By comparing these sequences to those deduced from DNA, it was established that the M and L subunits are post-translationally modified to remove the aminoterminal Met, whereas the H subunit is not. Inhibition of O/sub 2/ evolution in photosystem II particles from spinach by naphthoquinone derivatives show O/sub 2/ inhibition by bromomethyl and acetoxymethyl derivatives but not with hydroxymethyl derivatives. Inhibition by acetoxymethyl derivatives in irreversible and dependent on illumination suggesting that reduction of the quinone is necessary. Therefore acetoxymethyl derivatives may be useful as suicide reagents for labelling quinone binding sites. Procedures were developed to extract one or both of the quinones present in reaction centers and preserve the integrity of the co-factor binding sites. The H and M subunits were cleaned using furmic acid. Both fragments were isolated from the H subunit, while the larger fragment was isolated from the M subunit. Electrophoretic mobilities of the isolated fragments agrees well with the expected molecular weights. The L subunit was digested with Staphylococcus areus vs protease. The pattern obtained was consistant with the potential sites of cleavage, but it was not possible to assign cleavage sites unambiguously. 112 references, 37 figures, 2 tables.

Worland, S.T.

1984-09-01

400

Induction of Extracellular Hydroxyl Radical Production by White-Rot Fungi through Quinone Redox Cycling?  

PubMed Central

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 Fe3+-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 (H2O2 + Fe2+ ? OH + OH? + Fe3+). H2O2 production, Fe3+ 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 H2O2 levels and Fe3+ 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.

Gomez-Toribio, Victor; Garcia-Martin, Ana B.; Martinez, Maria J.; Martinez, Angel T.; Guillen, Francisco

2009-01-01

401

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

402

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

403

Antiparasitic activities of novel ruthenium/lapachol complexes.  

PubMed

The present study describes the synthesis, characterization, antileishmanial and antiplasmodial activities of novel diimine/(2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 4,4'-methylbipyridine (Me-bipy) and 4,4'-methoxybipyridine (MeO-bipy)/phosphine/ruthenium(II) complexes containing lapachol (Lap, 2-hydroxy-3-(3-33 methyl-2-buthenyl)-1,4-naphthoquinone) as bidentate ligand. The [Ru(Lap)(PPh3)2(bipy)]PF6 (1), [Ru(Lap)(PPh3)2(Me-bipy)]PF6 (2), [Ru(Lap)(PPh3)2(MeO-bipy)]PF6(3) and[Ru(Lap)(PPh3)2(phen)]PF6 (4) complexes, PPh3=triphenylphospine, were synthesized from the reactions of cis-[RuCl2(PPh3)2(X-bipy)] or cis-[RuCl2(PPh3)2(phen)], with lapachol. The [RuCl2(Lap)(dppb)] (5) [dppb=1,4-bis(diphenylphosphine)butane] was synthesized from the mer-[RuCl3(dppb)(H2O)] complex. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV-vis spectroscopy, (31)P{(1)H} and (1)H NMR, and cyclic voltammetry. The Ru(III) complex, [RuCl2(Lap)(dppb)], was also characterized by the EPR technique. The structure of the complexes [Ru(Lap)(PPh3)2(bipy)]PF6 and [RuCl2(Lap)(dppb)] was elucidated by X-ray diffraction. The evaluation of the antiparasitic activities of the complexes against Leishmania amazonensis and Plasmodium falciparum demonstrated that lapachol-ruthenium complexes are more potent than the free lapachol. The [RuCl2(Lap)(dppb)] complex is the most potent and selective antiparasitic compound among the five new ruthenium complexes studied in this work, exhibiting an activity comparable to the reference drugs. PMID:24727183

Barbosa, Marília I F; Corrêa, Rodrigo S; de Oliveira, Katia Mara; Rodrigues, Claudia; Ellena, Javier; Nascimento, Otaciro R; Rocha, Vinícius P C; Nonato, Fabiana R; Macedo, Taís S; Barbosa-Filho, José Maria; Soares, Milena B P; Batista, Alzir A

2014-07-01

404

Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin ?1 expression and the ERK1/2 signaling pathway.  

PubMed

Integrin ?1 facilitates cancer cell adhesion, migration and metastasis by activating intracellular signaling pathways including the ERK and PI3K signaling pathways. In previous studies, shikonin, an active naphthoquinone isolated from the Chinese medicine Zi Cao (gromwell), showed effective anticancer activity both in vivo and in vitro. However, the mechanisms underlying shikonin's anticancer activity are not fully elucidated. Increasing evidence indicates that shikonin inhibits tumor metastasis, but little is known about the effect of shikonin on lung cancer cells. To better understand the anti-metastatic role of shikonin in lung cancer, in this study we sought to investigate the effect of shikonin on lung cancer cell proliferation, adhesion to extracellular matrices (ECM), migration and invasion in non-small cell lung cancer A549 cells. We also sought to investigate the molecular mechanisms underlying shikonin's anticancer effects. Here we showed that when non-small cell lung cancer A549 cells were treated with shikonin for 24h, 8.0?M shikonin significantly inhibited cell proliferation, while cells treated with less than 2.0?M shikonin for 24h significantly suppressed cell adhesion to the ECM, invasion and migration in a dose-dependent manner. Moreover, real-time PCR and Western blot analysis showed that shikonin led to a reduction in the expression of integrin ?1 at the mRNA and protein levels. Further elucidation of the mechanisms involved revealed that shikonin repressed the phosphorylation of extracellular signal-regulated kinase (ERK1/2). Taken together, our findings provide new evidence that shikonin suppresses lung cancer invasion and metastasis by inhibiting integrin ?1 expression and the ERK1/2 signaling pathway. PMID:23562787

Wang, Heyong; Wu, Chunlian; Wan, Shengbang; Zhang, Huijun; Zhou, Songwen; Liu, Gentao

2013-06-01

405

Secreted pitfall-trap fluid of carnivorous Nepenthes plants is unsuitable for microbial growth  

PubMed Central

Background and Aims Carnivorous plants of the genus Nepenthes possess modified leaves that form pitfall traps in order to capture prey, mainly arthropods, to make additional nutrients available for the plant. These pitchers contain a digestive fluid due to the presence of hydrolytic enzymes. In this study, the composition of the digestive fluid was further analysed with regard to mineral nutrients and low molecular-weight compounds. A potential contribution of microbes to the composition of pitcher fluid was investigated. Methods Fluids from closed pitchers were harvested and analysed for mineral nutrients using analytical techniques based on ion-chromatography and inductively coupled plasma–optical emission spectroscopy. Secondary metabolites were identified by a combination of LC-MS and NMR. The presence of bacteria in the pitcher fluid was investigated by PCR of 16S-rRNA genes. Growth analyses of bacteria and yeast were performed in vitro with harvested pitcher fluid and in vivo within pitchers with injected microbes. Key Results The pitcher fluid from closed pitchers was found to be primarily an approx. 25-mm KCl solution, which is free of bacteria and unsuitable for microbial growth probably due to the lack of essential mineral nutrients such as phosphate and inorganic nitrogen. The fluid also contained antimicrobial naphthoquinones, plumbagin and 7-methyl-juglone, and defensive proteins such as the thaumatin-like protein. Challenging with bacteria or yeast c