Sample records for naphthoquinones

  1. [Naphthoquinones and their pharmacological properties].

    PubMed

    Babula, P; Adam, V; Havel, L; Kizek, R

    2007-06-01

    Naphthoquinones are wide-spread phenolic compounds in nature. They are products of bacterial and fungal as well as high-plants secondary metabolism. Juglone, lawsone, and plumbagin are the most widespread compounds. Naphthoquinones display very significant pharmacological properties--they are cytotoxic, they have significant antibacterial, antifungal, antiviral, insecticidal, anti-inflammatory, and antipyretic properties. Pharmacological effects to cardiovascular and reproductive systems have been demonstrated too. The mechanism of their effect is highly large and complex--they bind to DNA and inhibit the processes of replication, interact with numerous proteins (enzymes) and disturb cell and mitochondrial membranes, interfere with electrons of the respiratory chain on mitochondrial membranes. Plants with naphthoquinone content are widely used in China and the countries of South America, where they are applied to malignant and parasitic diseases treatment. PMID:17867522

  2. In vitro cytotoxicities of 1,4-naphthoquinone and hydroxylated 1,4-naphthoquinones to replicating cells.

    PubMed

    Babich, H; Stern, A

    1993-01-01

    Using the human hepatoma cell line, HepG2, and the BALB/c mouse fibroblast cell line, 3T3, as the bioindicators in the neutral red cytotoxicity assay, the effect of hydroxyl substitution on the toxicity of 1,4-naphthoquinone was studied. The sequence of potency for the quinones was 5,8-dihydroxy-1,4-naphthoquinone > 5-hydroxy-1,4-naphthoquinone > 1,4-naphthoquinone > 2-hydroxyl-1,4- naphthoquinone. Pretreatment of the cells with dicoumarol, an inhibitor of DT-diaphorase, enhanced the cytotoxicity of 1,4-naphthoquinone but not of the hydroxylated naphthoquinones. Pretreatment of the BALB/c cells with buthionine sulfoximine, an inhibitor of glutathione synthesis, enhanced the sensitivity of the cells to all the hydroxylated naphthoquinones but not to 1,4-naphthoquinone. A similar pretreatment of the HepG2 cells with buthionine sulfoximine enhanced the toxicity of the 2-hydroxy- and 5,8-dihydroxy-1,4-naphthoquinones but not of 5-hydroxy-1,4-naphthoquinone or of 1,4-naphthoquinone. Some differences were noted in the responses to the hydroxylated 1,4-naphthoquinones between buthionine sulfoximine-treated replicating cells and buthionine sulfoximine-treated isolated rat hepatocytes, a nonreplicating cell in culture. The use of a replicating cell system in studying the mechanisms of the cytotoxicity of quinones may be an important adjunct to studies using the isolated rat hepatocytes, which is the standard model system. PMID:7505009

  3. Antimicrobial activity of naphthoquinones from fusaria.

    PubMed

    Baker, R A; Tatum, J H; Nemec, S

    1990-07-01

    Twenty-two naphthoquinone compounds isolated or derived synthetically from culture extracts of Fusarium solani and F. oxysporum were examined for antimicrobial activity. Fifteen exhibited antibiotic activity against Staphylococcus aureus, and 12 were active against Streptococcus pyogenes, but none were active at the highest rate of 128 micrograms/ml against Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Serratia marcescens, or Pseudomonas aeruginosa. Of 8 plant pathogenic bacteria tested against 11 naphthoquinones, Corynebacterium poinsettiae was inhibited by 6 compounds, and Pseudomonas viridiflava was weakly inhibited by one. Only one of a group of 6 fluorescent soil pseudomonads was inhibited by one naphthoquinone. Antifungal activity of 10 compounds against 8 fungal plant pathogens was limited to inhibition of Phytophthora parasitica by one naphthopyran. PMID:2233983

  4. Variations in product in reactions of naphthoquinone with primary amines

    PubMed Central

    Singh, Marjit W; Karmakar, Anirban; Barooah, Nilotpal; Baruah, Jubaraj B

    2007-01-01

    Reaction of 1,2-naphthoquinone with primary amines gives a 2-amino-1,4-naphthoquinone derivative which is equivalent to 1,2 to 1,4 carbonyl transposition. For example the reaction of 1,2-naphthoquinone with 4-methoxyaniline gives 2-(4-methoxyanilino)-naphthoquinone-1,4-(4-methoxyanil) (1) and with n-butylamine gives 2-(butylamino)-naphthoquinone-1,4-butylimine (2) respectively. The compounds 1 and 2 are characterized by X-ray crystallography; they have hydrogen-bonded dimeric structures. Similar reaction of 1,4-naphthoquinone with 3-picolylamine and 4-picolylamine gives the corresponding 2-amino 1,4-naphthoquinones; two products are characterized by X-ray crystallography. The reaction of 1,4-naphthoquinone with 4-aminothiophenol and 1,4-naphthoquinone with 4-aminophenol are compared. The former leads to C-S and the latter to C-N bond formation. The reaction of 1,4-naphthoquinone with 4-aminothiophenol in an NMR tube is studied to explain that 2-(4-anilinothiolato) 1,4-naphthoquinone derivative to be the sole product in the reaction. PMID:17331232

  5. Leishmanicidal activity of two naphthoquinones against L. donovani

    PubMed Central

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

    2013-01-01

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

  6. Differential toxicity of juglone (5-hydroxy-1,4-naphthoquinone) and related naphthoquinones to saturniid moths

    Microsoft Academic Search

    Robert L. Thiboldeaux; Richard L. Lindroth; James W. Tracy

    1994-01-01

    The preferred hosts of the saturniid mothActias luna include members of the Juglandaceae, whose foliage contain the toxin juglone (5-hydroxy-1,4-naphthoquinone). The performance ofActias luna andCallosamia promethea was compared when fourth-instar larvae of each were fed birch foliage, a mutually acceptable food plant, or birth supplemented with 0.05% (w\\/w) juglone.A. luna fed juglone exhibited no changes in developmental time or mortality

  7. The chemical biology of naphthoquinones and its environmental implications.

    PubMed

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

    2012-01-01

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

  8. Naphthalene SOA: redox activity and naphthoquinone gas-particle partitioning

    NASA Astrophysics Data System (ADS)

    McWhinney, R. D.; Zhou, S.; Abbatt, J. P. D.

    2013-10-01

    Chamber secondary organic aerosol (SOA) from low-NOx photooxidation of naphthalene by hydroxyl radical was examined with respect to its redox cycling behaviour using the dithiothreitol (DTT) assay. Naphthalene SOA was highly redox-active, consuming DTT at an average rate of 118 ± 14 pmol per minute per ?g of SOA material. Measured particle-phase masses of the major previously identified redox active products, 1,2- and 1,4-naphthoquinone, accounted for only 21 ± 3% of the observed redox cycling activity. The redox-active 5-hydroxy-1,4-naphthoquinone was identified as a new minor product of naphthalene oxidation, and including this species in redox activity predictions increased the predicted DTT reactivity to 30 ± 5% of observations. These results suggest that there are substantial unidentified redox-active SOA constituents beyond the small quinones that may be important toxic components of these particles. A gas-to-SOA particle partitioning coefficient was calculated to be (7.0 ± 2.5) × 10-4 m3 ?g-1 for 1,4-naphthoquinone at 25 °C. This value suggests that under typical warm conditions, 1,4-naphthoquinone is unlikely to contribute strongly to redox behaviour of ambient particles, although further work is needed to determine the potential impact under conditions such as low temperatures where partitioning to the particle is more favourable. Also, higher order oxidation products that likely account for a substantial fraction of the redox cycling capability of the naphthalene SOA are likely to partition much more strongly to the particle phase.

  9. Effects of different carbon and nitrogen sources on naphthoquinone production of Cordyceps unilateralis BCC 1869.

    PubMed

    Prathumpai, W; Kocharin, K; Phimmakong, K; Wongsa, P

    2007-02-01

    The production of six naphthoquinone derivatives, erythrostominone, deoxyerythrostominone, 4-O-methyl erythrostominone, epierythrostominol, deoxyerythrostominol, and 3,5,8-trihydroxy-6-methoxy-2-(5-oxohexa- 1,3-dienyl)-1,4-naphthoquinone, was examined during the growth of Cordyceps unilateralis BCC 1869 on different carbon and nitrogen sources. Erythrostominone production by the fungus accounted for more than 50% of total naphthoquinones, but production of each of the other five derivatives accounted for less than 20% of total naphthoquinones. The highest volumetric production rate of erythrostominone and overall naphthoquinone production rate were obtained on mannose as a sole carbon source and ammonium sulfate as a sole nitrogen source (4922.4 +/- 118.8 mg/[L.d] and 5.03 g/[L.d], respectively). The highest growth rate was obtained on arabinose (0.043 h-1), whereas the maximum overall naphthoquinone concentration was obtained on lactose (2 g/L) at 237 h. These naphthoquinones were produced with no pH control and were first detected at a pH of about 3.0 to 4.0. These results suggest that carbon and nitrogen influenced directly the production of naphthoquinones. PMID:17496342

  10. 1,4-naphthoquinones: from oxidative damage to cellular and inter-cellular signaling.

    PubMed

    Klotz, Lars-Oliver; Hou, Xiaoqing; Jacob, Claus

    2014-01-01

    Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others) to cellular and inter-cellular signaling processes are discussed: (i) naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii) the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings. PMID:25232709

  11. Synthesis of novel naphthoquinone aliphatic amides and esters and their anticancer evaluation.

    PubMed

    Kongkathip, Boonsong; Akkarasamiyo, Sunisa; Hasitapan, Komkrit; Sittikul, Pichamon; Boonyalai, Nonlawat; Kongkathip, Ngampong

    2013-02-01

    Fourteen new naphthoquinone aliphatic amides and seventeen naphthoquinone aliphatic esters were synthesized in nine to ten steps from 1-hydroxy-2-naphthoic acid with 9-25% overall yield for the amides, and 16-21% overall yield for the esters. The key step of the amide synthesis is a coupling reaction between amine and various aliphatic acids using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as a coupling agent while for the ester synthesis, DCC/DMAP or CDI was used as the coupling reagent between aliphatic acids and naphthoquinone alcohol. Both naphthoquinone amides and esters were evaluated for their anticancer activity against KB cells. It was found that naphthoquinone aliphatic amides showed stronger anticancer activity than those of the esters when the chains are longer than 7-carbon atoms. The optimum chain of amides is expected to be 16-carbon atoms. In addition, naphthoquinone aliphatic esters with ?-methyl on the ester moiety possessed much stronger anticancer activity than the straight chains. Decatenation assay revealed that naphthoquinone amide with 16-carbon atoms chain at 15 ?M and 20 ?M can completely inhibit hTopoII? activity while at 10 ?M the enzyme activity was moderately inhibited. Molecular docking result also showed the same trend as the cytotoxicity and decatenation assay. PMID:23313636

  12. First synthesis and anticancer activity of novel naphthoquinone amides.

    PubMed

    Pradidphol, Narathip; Kongkathip, Ngampong; Sittikul, Pichamon; Boonyalai, Nonlawat; Kongkathip, Boonsong

    2012-03-01

    Sixteen novel naphthoquinone aromatic amides were synthesized by a new route starting from 1-hydroxy-2-naphthoic acid in nine or ten steps with good to excellent yield. Amide formation reaction was carried out by using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as an efficient condensing agent leading to carboxamides in high yield. The key step for converting naphthol to 3-hydroxynaphthoquinone was the Fremy's salt oxidation followed by hydroxylation with tert-butyl hydroperoxide and triton B. Anticancer activity of these new naphthoquinone amides were evaluated and benzamide 22 showed potent inhibition against NCI-H187 cell lines while naphthamides 23 and 43 were the most potent inhibition against KB cells. The decatenation assay revealed that compounds 24 and 43 at 20 ?M can inhibit hTopoII? activity while three other compounds, namely compounds 22, 23, and 45, exhibited hTopoII? inhibitory activity at final concentration of 50 ?M. Docking experiment revealed the same trend as the cytotoxicity and decatenation assay. Therefore, naphthamides 24 and 43 can be promising target molecules for anticancer drug development. PMID:22280818

  13. In vitro cytotoxicity activity of Diosquinone, a naphthoquinone epoxide.

    PubMed

    Adeniyi, B A; Robert, M F; Chai, H; Fong, H H S

    2003-03-01

    Diosquinone [1], a naphthoquinone epoxide previously isolated from the root bark of Diospyros mespiliformis (Hostch) and D. tricolor [Ebenaceae] is been assessed for cytotoxicity activity against ten cancer cell lines by standard NIH method. The ethno-pharmacological claim of this plant and the previously observed good antibacterial activity of this compound among the others isolated from this plant suggest its probable cytotoxicity activity. Diosquinone was observed to be very active against most of the cancer cell lines. It shows very good activity against all the cell lines tested with ED50 value ranging between 0.18 microg/ml. against Human Glioblastoma (U373) to 4.5 microg/ml. against Hormone dependent human prostrate cancer( LNCaP). PMID:12672163

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

    PubMed Central

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

    2014-01-01

    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

  15. Antitumoral activity of new polyamine-naphthoquinone conjugates.

    PubMed

    Esteves-Souza, Andressa; Lucio, Kelly Araújo; Da Cunha, Andréa Sousa; Da Cunha Pinto, Angelo; Da Silva Lima, Edson Luiz; Camara, Celso Amorim; Vargas, Maria Domingues; Gattass, Cerli Rocha

    2008-07-01

    Polyamine-naphthoquinone conjugates 5a-c were synthesized by nucleophilic displacement of 2-methoxy-lawsone 3a, 2-methoxylapachol 3b and 2-methoxy-nor-lapachol 3c with the polyamine N1-Boc-N5-Bn-spermidine 4. Unprotected derivatives 6a-c were synthesized to evaluate the effect of the protective Boc group on the activity of compounds 5a-c. The colorimetric MTT assay was used to evaluate their cytotoxic activity. All compounds were active against human lines of promyelocytic leukemia (HL-60), lung cancer (GLC4), Burkitt lymphoma (Daudi) and a mouse breast tumor (Ehrlich carcinoma), but only unprotected 6a-c showed activity against the human line of melanoma (MV-3). IC50 values were obtained from dose response curves by linear regression. DNA fragmentation was measured by quantification of the subG1 peak of the cell cycle. Apoptosis of HL-60 treated with 5c was dose-dependent. The amount of DNA fragmentation observed by exposure of HL-60 to 25 microM of compounds 5a-c and 6a-c is compatible with the decrease in viability induced by the drugs at this concentration. Production of ROS was measured by H2-CFDA. Kinetics of HL-60 DNA fragmentation and ROS formation by 5c indicated that production of ROS precedes cell death. In conclusion, spermidine-1,4-naphthoquinone conjugates exhibited an increase in activity compared with the natural products and induced apoptosis of tumor cell lines by a mechanism that is mediated, at least in part, by ROS production. PMID:18575741

  16. Induction of topoisomerase II-mediated DNA cleavage by the plant naphthoquinones plumbagin and shikonin.

    PubMed Central

    Fujii, N; Yamashita, Y; Arima, Y; Nagashima, M; Nakano, H

    1992-01-01

    Plumbagin and shikonin, plant metabolites which have naphthoquinone structures, induced mammalian topoisomerase II-mediated DNA cleavage in vitro. Treatment of a reaction mixture containing these naphthoquinones and topoisomerase II at an elevated temperature (65 degrees C) resulted in a great reduction in DNA cleavage, suggesting that the mechanism of the topoisomerase II-mediated DNA cleavage induced by these naphthoquinones is through formation of a cleavable complex, as seen with antitumor agents such as 4'-(9-acridinylamino)methanesulfon-m-anisidide and demethylepipodophyllotoxin ethylidene-beta-glucoside. Lawson and lapacol, which are structurally related plant metabolites with naphthoquinone moieties, could not induce topoisomerase II-mediated DNA cleavage. Plumbagin and shikonin induced a similar DNA cleavage pattern with topoisomerase II which was different from the cleavage patterns induced with other known topoisomerase II-active drugs. A DNA-unwinding assay with T4 DNA ligase showed that shikonin, lawson, and lapacol did not intercalate into DNA, while plumbagin and 2-methyl-1,4-naphthoquinone intercalate into DNA, but to a lower degree than 4'-(9-acridinylamino)methanesulfon-m-anisidide does. Images PMID:1336338

  17. Effect of hydroxy substituent on the prooxidant action of naphthoquinone compounds.

    PubMed

    Murakami, Keiko; Haneda, Miyako; Iwata, Shouko; Yoshino, Masataka

    2010-04-01

    Prooxidant activity of naphthoquinone compounds was analyzed by lipid peroxidation, and the formation of base adduct in DNA. Naphthoquinones with electron-repelling hydroxyl group in the benzene moiety such as juglone and shikonin of lower concentrations stimulated the microsomal lipid peroxidation, but lawsone and lapachol with hydroxyl group in the quinone moiety did not enhance the formation of lipid peroxides. Naphthoquinone-dependent lipid peroxidation was closely related to the enhancement of Fe(2+) autooxidation. Treatment of DNA with juglone a representative of 5-hydroxylated naphthoquinone stimulated the formation of 8-hydroxy-2'-deoxyguanosine, whereas lawsone and lapachol showed negligible formation of DNA base adduct. ESR spectra showed that juglone can form semiquinone radical in the presence of ferrous ion, but lawsone cannot. Biological toxicity of juglone with the potent electron-repelling group at 5-position may be due to the reactive oxygen species formed by semiquinone radical, but naphthoquinone compounds with an electron-repelling group in the quinone moiety, lawsone shows weak toxicity with only a little ability producing reactive oxygen species by the negligible formation of semiquinone. PMID:19961919

  18. Eleutherinone, a novel fungitoxic naphthoquinone from Eleutherine bulbosa (Iridaceae).

    PubMed

    Alves, Tânia Maria Almeida; Kloos, Helmut; Zani, Carlos Leomar

    2003-07-01

    The dichloromethane extract prepared from the underground parts of Eleutherine bulbosa (Miller) Urban (Iridaceae) showed strong activity in the direct bioautography assay with the phytopathogenic fungus Cladosporium sphaerospermum. This assay was used to guide the fractionation of this extract and allowed the isolation of four compounds: the new naphthoquinone eleutherinone[8-methoxy-1-methyl-1,3-dihydro-naphtho(2,3-c)furan-4,9 -dione] and the known compounds, previously isolated from this species, eleutherin [9-methoxy-1(R),3(S)-dimethyl-3,4-dihydro-1H-benzo(g)isochromene-5,10-dione], isoeleutherin [9-methoxy-1(R),3(R)-dimethyl-3,4-dihydro-1H-benzo(g)isochromene-5,10-dione], and eleutherol [4-hydroxy-5-methoxy-3(R)-methyl-3H-naphtho(2,3-c)furan-1 -one]. All quinonoid compounds showed strong antifungal activity in the bioautography assay at 100 g/spot, while eleutherol was inactive. PMID:12973542

  19. Synthesis and biological evaluation of novel ferrocene-naphthoquinones as antiplasmodial agents.

    PubMed

    García-Barrantes, Pedro M; Lamoureux, Guy V; Pérez, Alice L; García-Sánchez, Rory N; Martínez, Antonio R; San Feliciano, Arturo

    2013-01-01

    This work deals with the synthesis and evaluation of new compounds designed by combination of 1,4-naphthoquinone and ferrocene fragments in a 3-ferrocenylmethyl-2-hydroxy-1,4-naphthoquinone arrangement. A practical coupling reaction between 2-hydroxy-1,4-naphthoquinone and ferrocenemethanol derivatives has been developed. This procedure can be carried out "on-water", at moderate temperatures and without auxiliaries or catalysts, with moderate to high yields. The synthesized derivatives have shown significant in vitro antiplasmodial activity against chloroquine-sensitive and resistant Plasmodium falciparum strains and it has been shown that this activity is not related to the inhibition of biomineralization of ferriprotoporphyrin IX. Binding energy calculations and docking of these compounds to cytochrome b in comparison with atovaquone have been performed. PMID:24211630

  20. Synthesis and preliminary pharmacological evaluation of new (+/-) 1,4-naphthoquinones structurally related to lapachol.

    PubMed

    da Silva, Alcides J M; Buarque, Camilla D; Brito, Flávia V; Aurelian, Laure; Macedo, Luciana F; Malkas, Linda H; Hickey, Robert J; Lopes, Daniele V S; Noël, François; Murakami, Yugo L B; Silva, Noelson M V; Melo, Paulo A; Caruso, Rodrigo R B; Castro, Newton G; Costa, Paulo R R

    2002-08-01

    Seven new 1,4-naphthoquinones structurally related to lapachol were synthesized from lawsone and oxygenated arylmercurials. These compounds can also be seen as pterocarpan derivatives where the A-ring was substituted by the 1,4-naphthoquinone nucleus. Pharmacological screening provided evidence of significant biological activities, including effects against proliferation of the MCF-7 human breast cancer cell line, against Herpes Simplex Virus type 2 infection, and against snake poison-induced myotoxicity. One derivative displaced flunitrazepam binding and showed benzodiazepine-like activity, suggesting novel neuroactive structural motifs. PMID:12057662

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

    PubMed

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

    2008-06-01

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

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

    PubMed

    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

    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

  3. 5-Hydroxy-1,4-naphthoquinone (juglone) and 2-hydroxy-1,4-naphthoquinone (lawsone) influence on jack bean urease activity: Elucidation of the difference in inhibition activity.

    PubMed

    Kot, Miros?awa; Karcz, Waldemar; Zaborska, Wies?awa

    2010-06-01

    The aim of this study was elucidation of the difference in inhibition influence of 5-hydroxy-1,4-naphthoquinone (juglone) and 2-hydroxy-1,4-naphthoquinone (lawsone) on jack bean urease activity. It was found that juglone acted as a strong, time and concentration dependent inactivator of urease. On the contrary, lawsone showed an inconsiderable inhibition influence. The reactivation of juglone modified urease showed the participation of reversible and irreversible contribution in the inactivation. In the presence of an excess of DTT, urease inactivated by juglone regained 70% of its activity. The reversible inactivation was attributed to oxidation of the essential urease thiols by reactive oxygen species (ROS) realizing during reduction of juglone to seminaphthoquinone. Presence of hydrogen peroxide in the incubation system was proved by direct determination and by application of catalase. The irreversible contribution in the inhibition was assumed as an arylation of urease thiol groups by juglone. The insignificant urease inhibition by lawsone was concluded as an effect of a low hydrogen peroxide generation and lawsone resistance for reaction with protein thiols. It was found that lawsone well reacted with l-cysteine, poorly with glutathione and hardly with urease thiols. The observed sequence was arranged according the rule the more complex thiol the less susceptible for reaction with lawsone. On the other hand, juglone displayed an excellent reactivity towards both thiols and urease. Thus, this indicated a significance of a steric hindrance which appeared when the hydroxyl group changing position from 5 in juglone (5-hydroxy-1,4-naphthoquinone) to 2 in lawsone (2-hydroxy-1,4-naphthoquinone). PMID:20202666

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

    PubMed

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

    1995-10-01

    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

  5. Differentiating biochemical mechanisms of toxicity for substituted 1,4-naphthoquinones using rainbow trout kepatocytes

    SciTech Connect

    Schmieder, P.; Hammermeister, D.; Kolanczyk, R.; Hoffman, A.; Fitzsimmons, P.; Lien, G.; Johnson, R.; Serrano, J. [Environmental Protection Agency, Duluth, MN (United States). Environmental Research Lab.; Keogh, K.; Spizzo, T. [Univ. of Minnesota, Duluth, MN (United States)

    1995-12-31

    An in vitro assay system is being developed to discriminate biochemical mechanisms of electrophilic- and free radical-mediated toxicity in fish species. Information gained from the assay system will be used in development of mechanistically-based QSARs. Rainbow trout (Oncorhynchus mykiss) hepatocytes are isolated and held in suspension culture for 7h. Extracellular and intracellular toxicant concentration is monitored throughout the exposures in conjunction with a series of biochemical parameters to assess cell viability (LDH leakage, dye exclusion), cellular energy status (ATP, ADP, AMP, and energy charge), reducing equivalents (NADPH, NADP, NADH, NAD), glutathione status (GSH and GSSG), and reactive oxygen species. Differential interference contrast microscopy is also used to describe cellular changes in response to intoxication. Substituted naphthoquinones (1,4-naphthoquinone, 2-methyl-1,4-naphthoquinone, and 2,3-dimethoxy 1,4-naphthoquinone) were used to test the ability of the assay system to discriminate toxic responses resulting primarily from redox cycling, alkylation, or a mixture of the two mechanisms. The magnitude and time-course of biochemical alterations detected in-response to each toxicant is presented. The ability of the assay system to profile mechanisms of reactive chemical toxicity will be validated with additional chemicals of ``known`` mechanism. once validated the system will be used in conjunction with computational chemistry research to help verify chemical structural attributes associated with mechanisms of toxicity, ultimately for the development of predictive toxicological models.

  6. Diospyrone, crassiflorone and plumbagin: three antimycobacterial and antigonorrhoeal naphthoquinones from two Diospyros spp

    Microsoft Academic Search

    Victor Kuete; Jean G. Tangmouo; J. J. Marion Meyer; Namrita Lall

    2009-01-01

    The aim of this study was to evaluate the antimycobacterial and antigonorrhoeal activities of three naphthoquinones (diospyrone, crassiflorone and plumbagin) from Diospyros canaliculata and Diospyros crassiflora as well as the crude extracts from these plants. The agar disk diffusion assay, broth microdilution method, microplate Alamar blue assay (MABA) and radiometric respiratory technique using the BACTEC 460 TB system were used.

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

    PubMed Central

    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

    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

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

    PubMed

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

    2014-05-01

    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

  9. Mutagenicity and cytotoxicity of naphthoquinones for Ames Salmonella tester strains

    SciTech Connect

    Hakura, Atsushi; Mochida, Hisatoshi; Tsutsui, Yoshie; Yamatsu, Kiyomi [Eisai Co., Ltd., Tsukuba-shi (Japan)

    1994-07-01

    The molecular mechanisms involved in quinone cytotoxicity, especially mutagenicity, are still largely unknown. In order to better understand the molecular aspects of the mechanisms of quinone mutagenicity and cytotoxicity, we examined them by using a series of 13 simple structural naphthoquinone (NQ) derivatives for 9 Ames Salmonella mutagenicity tester strains in the presence or absence of liver homogenate S9 mix from rats induced with phenobarbital and 5,6-benzoflavone. Most NQs used in this study showed mutagenicity with and/or without S9 mix. The most potent mutagenic NQ was 2,3-dichloro-1,4-NQ, with mutagenicity of 18 induced revertents/nmol/plate for strain TA104 without S9 mix. Among the strains used, TA104, which is sensitive to oxidative mutagens, was the most sensitive to the NQs, and the second most sensitive strain was TA2637, which detects bulky DNA adducts. The relationship of mutagenic potency to the one-electron reduction potential with TA104 suggested that the higher redox potential NQs were more mutagenic than the lower redox potential NQs. The cytotoxic effect of the NQs was largely dependent on the structures of their substituents. It was suggested that the higher redox potential NQs were more cytotoxic than the lower redox potential NQs for all of the strains used, in contrast to the mutagenicity of the NQs. The presence of S9 mix decreased the cytotoxic effect of the NQs, the extent of which was also largely dependent on the structures of their substituents and is in accordance with the order of the height of the one-electron reduction potentials. These results indicate that the mutagenicity of NQs in Salmonella typhimurium was due to oxidative damage produced with activated oxygen species such as hydroxy radical and superoxide anion radical, which are generated as a result of the reduction of the NQs, and to bulky NQ-DNA adducts accounting for their electrophilic property, whose contribution was largely dependent on the substituents of NQs.

  10. New naphthoquinones and an alkaloid with in vitro activity against Toxoplasma gondii RH and EGS strains.

    PubMed

    Ferreira, Ronize Andréia; de Oliveira, Alaide Braga; Gualberto, Simone Andrade; Miguel Del Corral, José M; Fujiwara, Ricardo Toshio; Gazzinelli Guimarães, Pedro Henrique; de Almeida Vitor, Ricardo Wagner

    2012-12-01

    The efficacy of three amino-terpenyl naphthoquinones and the alkaloid liriodenine were examined against tachyzoites and tissues cysts of the RH and EGS strains, respectively. Monolayers of 2C4 fibroblasts infected with tachyzoites of the RH strain were incubated with different concentrations of the compounds for 48 h. Specifically, 7-(4-methyl-3-pentenyl)-2-pyrrolidine-[1,4]-naphthoquinone (QUI-5), 6-(4-methyl-3-pentenyl)-2-pyrrolidine-[1,4]-naphthoquinone (QUI-6), 6-(4-methylpentyl)-2-pyrrolidine-[1,4]-naphthoquinone (QUI-11), and 8 h-benzo[g]-1,3-benzodioxolo[6,5,4-de]quinolin-8-one,9Cl-1,2-methylene dioxiaporfina (liriodenine) inhibited intracellular replication of T. gondii. The IC(50) values obtained for compounds QUI-5 and QUI-6 were 69.35 and 172.81 ?M (i.e., 21.4 and 53.4 ?g/mL), respectively. The naphthoquinone QUI-11 and liriodenine significantly inhibited intracellular replication of T. gondii. The IC(50) values obtained with these experiments were 0.32 and 0.07 ?M (i.e., 0.1 and 0.02 ?g/mL), respectively. Compounds QUI-5, QUI-6, QUI-11 and liriodenine demonstrated lower toxicity for 2C4 fibroblasts compared to atovaquone. In addition, cysts isolated from the brains of mice chronically infected with the EGS strain were exposed to the compounds. Infectivity of the cysts after incubation with the compounds was assessed by infection of mice. The data obtained showed that in vitro incubation with QUI-6, QUI-11 and liriodenine inhibited the infectivity of the bradyzoites. This activity was time- and concentration-dependent. PMID:23000485

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

    Microsoft Academic Search

    Antonio Morello; Mario Pavani; Juan A. Garbarino; maría C. Chamy; Cristián Frey; Jerson Mancilla; aníbal Guerrero; Yolanda Repetto; Jorge Ferreira

    1995-01-01

    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

  12. DT-diaphorase-catalysed reduction of 1,4-naphthoquinone derivatives and glutathionyl-quinone conjugates. Effect of substituents on autoxidation rates.

    PubMed Central

    Buffinton, G D; Ollinger, K; Brunmark, A; Cadenas, E

    1989-01-01

    DT-diaphorase catalysed the reduction of 1,4-naphthoquinones with hydroxy, methyl, methoxy and glutathionyl substituents at the expense of reducing equivalents from NADPH. The initial rates of quinone reduction did not correlate with either the half-wave reduction potential (E1/2) value (determined by h.p.l.c. with electrochemical detection against an Ag/AgCl reference electrode) or the partition coefficient of the quinones. After their reduction by DT-diaphorase the 1,4-naphthoquinone derivatives autoxidized at distinct rates, the extent of which was influenced by the nature of the substituents. Thus for the 1,4-naphthoquinone series the following order of rate of autoxidation was found: 5-hydroxy-1,4-naphthoquinone greater than 3-glutathionyl-1,4-naphthoquinone greater than 5-hydroxy-3-glutathionyl-1,4-naphthoquinone greater than 1,4-naphthoquinone greater than 2-hydroxy-1,4-naphthoquinone. For the 2-methyl-1,4-naphthoquinone (menadione) series the following order was observed: 5-hydroxy-2-methyl-1,4-naphthoquinone greater than 3-glutathionyl-5-hydroxy-2-methyl-1,4-naphthoquinone greater than 3-glutathionyl-2-methyl-1,4-naphthoquinone greater than 2-methyl-1,4-naphthoquinone greater than 3-hydroxy-2-methyl-1,4-naphthoquinone. The autoxidized naphthohydroquinone derivatives were re-reduced by DT-diaphorase, thus closing a cycle of enzymic reduction in equilibrium autoxidation. This was expressed as an excess of NADPH oxidized over the initial concentration of quinone present as well as H2O2 formation. These findings demonstrate that glutathionyl conjugates of 1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone and those of their respective 5-hydroxy derivatives are able to act as substrates for DT-diaphorase and that they also autoxidize at rates higher than those for the unsubstituted parent compounds. These results are discussed in terms of the cellular role of DT-diaphorase in the reduction of hydroxy- or glutathionyl-substituted naphthoquinones as well as the further conjugation of these hydroquinones with glucuronide or sulphate within the cellular milieu, thereby facilitating their disposal from the cells. PMID:2494985

  13. Involvement of Akt in mitochondria-dependent apoptosis induced by a cdc25 phosphatase inhibitor naphthoquinone analog

    Microsoft Academic Search

    Hae Jong Kim; Seung Koo Kang; Jung Yee Mun; Young Jin Chun; Kyung Hee Choi; Mie Young Kim

    2003-01-01

    Vitamin K-related analogs induce growth inhibition via a cell cycle arrest through cdc25A phosphatase inhibition in various cancer cell lines. We report that 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (DDN), a naphthoquinone analog, induces mitochondria-dependent apoptosis in human promyelocytic leukemia HL-60 cells. DDN induced cytochrome c release, Bax translocation, cleavage of Bid and Bad, and activation of caspase-3, -8, -9 upon the induction of apoptosis.

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

    E-print Network

    Rodriguez Campos, Enrique

    1964-01-01

    -- naphthoquinone and menadione sodium bisulfite ~ ooo e ~ ~ ~ ~ Page 2. 5D Effect of concentrations of 1, 4- naphthoquinone and menadione sodium bisulfite on the percent of urediospore germination or P ci ' draaiaio tritici, c 29. . . . . . . . 16 Effect... of concentrations of 1, 4-naphtho- quinone and menadione sodium bisulfite on the percent of urediospore germination of Paced a 6 agio'8 t tt'cl, 56. . . . . . . . . . , 17 Effect of concentrations of 1, 4-naphtho- quinone and menadione sodium bisulfite...

  15. 1,4-Naphthoquinones as inducers of oxidative damage and stress signaling in HaCaT human keratinocytes.

    PubMed

    Klaus, Viola; Hartmann, Tobias; Gambini, Juan; Graf, Peter; Stahl, Wilhelm; Hartwig, Andrea; Klotz, Lars-Oliver

    2010-04-15

    Selected biological effects of 1,4-naphthoquinone, menadione (2-methyl-1,4-naphthoquinone) and structurally related quinones from natural sources--the 5-hydroxy-naphthoquinones juglone, plumbagin and the 2-hydroxy-naphthoquinones lawsone and lapachol--were studied in human keratinocytes (HaCaT). 1,4-naphthoquinone and menadione as well as juglone and plumbagin were highly cytotoxic, strongly induced reactive oxygen species (ROS) formation and depleted cellular glutathione. Moreover, they induced oxidative DNA base damage and accumulation of DNA strand breaks, as demonstrated in an alkaline DNA unwinding assay. Neither lawsone nor lapachol (up to 100 microM) were active in any of these assays. Cytotoxic and oxidative action was paralleled by stimulation of stress signaling: all tested quinones except lawsone and lapachol strongly induced phosphorylation of the epidermal growth factor receptor (EGFR) and the related ErbB2 receptor tyrosine kinase. EGFR activation by plumbagin, juglone and menadione was attenuated by a superoxide dismutase mimetic, indicating that ROS-related mechanisms contribute to EGFR activation by these naphthoquinones. PMID:20153715

  16. Structure-activity relationships in the haemolytic activity and nephrotoxicity of derivatives of 1,2- and 1,4-naphthoquinone.

    PubMed

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

    2007-01-01

    Naphthoquinone derivatives are under investigation as potential therapeutic agents. Some such compounds are known, however, to be toxic to both animals and humans. Many naphthoquinone derivatives are haemolytic agents, while others cause necrosis of tubular epithelial cells. In the present study, the short-term toxicity of 16 derivatives of 1,2- and 1,4-naphthoquinone has been examined in rats in order to give information on structure-activity relationships. All the naphthoquinones except one caused haemolytic anaemia, but only hydroxy and amino derivatives were nephrotoxic. Among derivatives of 2-amino-1,4-naphthoquinone, substitution in the 3-position decreased haemolytic activity and abolished nephrotoxicity. Methylation of the hydroxyl group of 2-hydroxy-1,4-naphthoquinone had a similar effect. In contrast, methylation of the amino group of 2-amino-1,4-naphthoquinone increased the severity of both haemolysis and renal damage. Among the 1,2-naphthoquinones tested, the 4-methoxy and 4-amino derivatives were more toxic than the corresponding 1,4-isomers, although 4-methyl-1,2-naphthoquinone was less toxic than 2-methyl-1,4-naphthoquinone. At present, the toxicity of naphthoquinone derivatives cannot accurately be predicted on the basis of their chemical structure. In developing naphthoquinone derivatives for use in humans, toxicological studies in animals should be conducted at an early stage, bearing in mind that clinical studies have shown that humans appear to be particularly vulnerable to the nephrotoxic action of these compounds, and that certain individuals are unusually susceptible to their haemolytic action. PMID:17265417

  17. 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

    Vrana, Oldrich; Adam, Vojtech

    2014-01-01

    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. PMID:25045679

  18. 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

    Vaverkova, Veronika; Vrana, Oldrich; Adam, Vojtech; Pekarek, Tomas; Jampilek, Josef; Babula, Petr

    2014-01-01

    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. PMID:25045679

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

    PubMed

    Sakunphueak, Athip; Panichayupakaranant, Pharkphoom

    2010-11-01

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

  20. Enantioselective epoxidation of chalcones and naphthoquinones mediated by (+)-norcamphor-derived hydroperoxide

    Microsoft Academic Search

    Alessandra Lattanzi; Maria Cocilova; Patrizia Iannece; Arrigo Scettri

    2004-01-01

    (+)-Norcamphor-derived hydroperoxide has been employed in the asymmetric epoxidation of electron poor alkenes such as trans-chalcones and naphthoquinones. Optimization of the reaction conditions required the employment of n-BuLi\\/THF at ?20°C to achieve ees up to 58%. The epoxide of vitamin K3 has now been obtained with the best up to now reported value of enantioselectivity (51% ee).

  1. Polyhalogenated benzo- and naphthoquinones are potent inhibitors of plant and bacterial ureases.

    PubMed

    Ashiralieva, Ainura; Kleiner, Diethelm

    2003-12-01

    Polyhalogenated benzo- and naphthoquinones were found to be potent inhibitors of pure ureases from Bacillus pasteurii and Canavalia ensiformis. They also inhibited ureases in whole cells of Helicobacter pylori, Klebsiella oxytoca and Proteus mirabilis. Inhibition was non-competitive with K(i) values in the micromolar range or below. Inhibition was irreversible as shown by equilibrium dialysis. Inhibitory power decreased considerably when halogens were replaced by -OH, -CN, alkoxy or alkyl groups. PMID:14644444

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

    Microsoft Academic Search

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

    2010-01-01

    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

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

    Microsoft Academic Search

    Ingrid L. I. Hook

    2001-01-01

    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

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

    PubMed

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

    2007-12-01

    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

  5. Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent.

    PubMed

    Moreira, Diogo R M; de Sá, Matheus S; Macedo, Taís S; Menezes, Maria N; Reys, José Rui M; Santana, Antônio E G; Silva, Thaissa L; Maia, Gabriela L A; Barbosa-Filho, José M; Camara, Celso A; da Silva, Tania M S; da Silva, Katia N; Guimaraes, Elisalva T; Dos Santos, Ricardo R; Goulart, Marília O F; Soares, Milena B P

    2015-08-01

    This study reports on the design, synthesis and antiparasitic activity of three new semi-synthetic naphthoquinones structurally related to the naturally-occurring lapachol and lapachone. Of the compounds tested, 3-(3-methylbut-1-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl acetate (1) was the most active against Plasmodium falciparum among both natural and semi-synthetic naphthoquinones, showing potent and selective activity. Compound 1 was able to reduce the in vitro parasite burden, in vitro parasite cell cycle, as well as the blood parasitemia in Plasmodium berghei-infected mice. More importantly, infection reduction under compound 1-treatment was achieved without exhibiting mouse genotoxicity. Regarding the molecular mechanism of action, this compound inhibited the hemozoin crystal formation in P. falciparum treated cells, and this was further confirmed by observing that it inhibits the ?-hematin polymerization process similarly to chloroquine. Interestingly, this compound did not affect either mitochondria structure or cause DNA fragmentation in parasite treated cells. In conclusion, we identified a semi-synthetic antimalarial naphthoquinone closely related to isolapachol, which had stronger antimalarial activity than lapachol. PMID:25431148

  6. Inhibition of 2-P-mercaptophenyl-1,4-naphthoquinone on human platelet function.

    PubMed

    Shen, A Y; Huang, M H; Teng, C M; Wang, J S

    1999-01-01

    As widely assumed, platelets and coagulation system heavily influence the pathogenesis and progression of cardiovascular diseases. Some 1,4-naphthoquinone derivatives, such as vitamin K3, have been reported to increase the synthesis of coagulation proteins. In this study, we examine how 2-p-mercaptophenyl -1,4-naphthoquinone (NTP), a newly synthesized 1,4-naphthoquinone derivative, affects the platelet function in humans. A tapered parallel plate chamber which provided a range of shear stress covering the entire physiological range in human circulation is used to assess platelet adhesiveness on fibrinogen coated-surface. In addition, platelet aggregation and thromboxane B2 (TXB2) production by inducers are evaluated by the turbidimetric method and enzyme immunoassay kit, respectively. Moreover, platelets [Ca2+]i are measured using a dual-wavelength fluorescence spectrophotometer. Analysis results indicate that 1) NTP decreases the percentages of attached platelets at the locations in various shear stresses and the levels of platelet adhesiveness, denoted as the slope; 2) NTP can inhibit the platelet aggregation by ADP (2 microM) and collagen (25 microg/ml), and the IC50 are: 0.32 and 26.83 microg/ml, respectively; and 3) NTP markedly inhibits TXB2 formation and platelet [Ca2+]i elevation caused by ADP and collagen. Therefore, we conclude that NTP may inhibit platelet adhesiveness on fibrinogen coated-surface, aggregability, [Ca2+]i, and thromboxane production, and that it may be used as an antiplatelet agent. PMID:10403492

  7. Synthetic 1,4-pyran naphthoquinones are potent inhibitors of dengue virus replication.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

    2014-01-01

    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

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

    PubMed Central

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

    2013-01-01

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

  10. 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

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

    2006-01-01

    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

  11. Synthesis of new 9-hydroxy-?- and 7-hydroxy-?-pyran naphthoquinones and cytotoxicity against cancer cell lines.

    PubMed

    da Rocha, David R; de Souza, Ana C G; Resende, Jackson A L C; Santos, Wilson C; dos Santos, Evelyne A; Pessoa, Cláudia; de Moraes, Manoel O; Costa-Lotufo, Letícia V; Montenegro, Raquel C; Ferreira, Vitor F

    2011-06-01

    A synthetic method to obtain ?- and ?-pyran naphthoquinones 10 and 11 with a hydroxyl substituent on the aromatic ring was developed. Two series of ?- and ?-pyran naphthoquinones were obtained from the 8-hydroxy-lawsone, and their anticancer properties were evaluated against four tumor cell lines. In general, the new compounds displayed good activity, possibly indicating that these compounds have increased pro-oxidant capacity. The 9-hydroxy-?-lapachone and 7-hydroxy-?-lapachone analogues of the natural products ?-lapachone and ?-lapachone were successfully produced by this methodology. PMID:21487631

  12. 1,4-Naphthoquinone Cations as Antiplasmodial Agents: Hydroxy-, Acyloxy-, and Alkoxy-Substituted Analogues

    PubMed Central

    2012-01-01

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

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

    PubMed

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

    1999-12-15

    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

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

    PubMed

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

    2005-08-15

    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

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

    PubMed Central

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

    1998-01-01

    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

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

    PubMed Central

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

    2010-01-01

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

  17. Targeting of Helicobacter pylori thymidylate synthase ThyX by non-mitotoxic hydroxy-naphthoquinones.

    PubMed

    Skouloubris, Stéphane; Djaout, Kamel; Lamarre, Isabelle; Lambry, Jean-Christophe; Anger, Karine; Briffotaux, Julien; Liebl, Ursula; de Reuse, Hilde; Myllykallio, Hannu

    2015-06-01

    ThyX is an essential thymidylate synthase that is mechanistically and structurally unrelated to the functionally analogous human enzyme, thus providing means for selective inhibition of bacterial growth. To identify novel compounds with anti-bacterial activity against the human pathogenic bacterium Helicobacter pylori, based on our earlier biochemical and structural analyses, we designed a series of eighteen 2-hydroxy-1,4-naphthoquinones (2-OH-1,4-NQs) that target HpThyX. Our lead-like molecules markedly inhibited the NADPH oxidation and 2'-deoxythymidine-5'-monophosphate-forming activities of HpThyX enzyme in vitro, with inhibitory constants in the low nanomolar range. The identification of non-cytotoxic and non-mitotoxic 2-OH-1,4-NQ inhibitors permitted testing their in vivo efficacy in a mouse model for H. pylori infections. Despite the widely assumed toxicity of naphthoquinones (NQs), we identified tight-binding ThyX inhibitors that were tolerated in mice and can be associated with a modest effect in reducing the number of colonizing bacteria. Our results thus provide proof-of-concept that targeting ThyX enzymes is a highly feasible strategy for the development of therapies against H. pylori and a high number of other ThyX-dependent pathogenic bacteria. We also demonstrate that chemical reactivity of NQs does not prevent their exploitation as anti-microbial compounds, particularly when mitotoxicity screening is used to prioritize these compounds for further experimentation. PMID:26040760

  18. Studies on the reactivity of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone: reactions with indole derivatives and other C-nucleophiles.

    PubMed

    Koulouri, Sofia; Malamidou-Xenikaki, Elizabeth; Spyroudis, Spyros; Tsanakopoulou, Maria

    2005-10-28

    [reaction: see text] Thermal decomposition of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone) in the presence of indole derivatives affords 3-acylated indoles existing in their enol forms, through a ring contraction and alpha,alpha'-dioxoketene formation reaction. The same reactants afford 3-(3-indolyl)-2-hydroxy-1,4-naphthoquinones in a copper-catalyzed reaction. Enamines, among other C-nucleophiles tested, give analogous results. PMID:16238309

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

    PubMed

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

    2014-04-23

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

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

    PubMed Central

    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

    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. PMID:23350008

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

    Microsoft Academic Search

    David Kirkland; Daniel Marzin

    2003-01-01

    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

  2. Synthesis, leishmanicidal activity and theoretical evaluations of a series of substituted bis-2-hydroxy-1,4-naphthoquinones.

    PubMed

    de Araújo, Morgana V; de Souza, Patricia S O; de Queiroz, Aline C; da Matta, Carolina B B; Leite, Anderson Brandão; da Silva, Amanda Evelyn; de França, José A A; Silva, Tania M S; Camara, Celso A; Alexandre-Moreira, Magna S

    2014-01-01

    A series of eight substituted bis-2-hydroxy-1,4-naphthoquinone derivatives was synthesized through lawsone condensation with various aromatic and aliphatic aldehydes under mild acidic conditions. The title compounds were evaluated for antileishmanial activity in vitro against Leishmania amazonensis and Leishmania braziliensis promastigotes; six compounds showed good activity without significant toxic effects. The compound with the highest activity was used for an in vivo assay with Leishmania amazonensis. PMID:25247686

  3. A survey on the reactivity of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone with amino compounds.

    PubMed

    Spagou, Konstantina; Malamidou-Xenikaki, Elizabeth; Spyroudis, Spyros

    2005-01-01

    The phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone reacts with aminoesters, ureas, aminoalcohols and aminophenols in refluxing dichloromethane to afford good yields of indanedione 2-carboxamido compounds, that in solution exist in an enol-amide form. The same reactants in a copper-catalyzed reaction afford mainly the corresponding N-arylo compounds. Arylhydrazines are mainly oxidized by the ylide and arylation occurs only in a low yield. PMID:18007290

  4. OCTAN-1-OL/WATER PARTITION COEFFICIENTS OF P-BENZO- AND P-NAPHTHOQUINONES CORRECTED FOR PH EFFECT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of pH of the aqueous phase on the octan-1-ol / water partition coefficients (kow) of quinones was demontrated. The kow of a series of p-benzo- and p-naphthoquinones were determined using a mildly buffered aqueous phase (1 mM Hepes, pH 7.0) to correct for the pH effects on the lipophilicit...

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

    PubMed

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

    2013-12-12

    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

  6. Herbicidal action of 2-hydroxy-3-alkyl-1,4-naphthoquinones.

    PubMed

    Jewess, Philip J; Higgins, James; Berry, Kate J; Moss, Stephen R; Boogaard, Adrian B; Khambay, Bhupinder P S

    2002-03-01

    The main mode of herbicidal activity of 2-hydroxy-3-alkyl-1,4-naphthoquinones is shown to be inhibition of photosystem II (PSII). The herbicidal and in vitro activities have been measured and correlated with their (Log)octanol/water partition coefficients (Log Ko/w). The length of the 3-n-alkyl substituent for optimal activity differed between herbicidal and in vitro activity. The maximum in vitro activity was given by the nonyl to dodecyl homologues (Log Ko/w between 6.54 and 8.12), whereas herbicidal activity peaked with the n-hexyl compound (Log Ko/w = 4.95). The effect of chain branching was also investigated using isomeric pentyl analogues substituted at position 3. All exhibited similar levels of in vitro activities but herbicidal activities differed, albeit moderately, with the exception of one analogue that was much less phytotoxic. Other modes of action were also investigated using two representative compounds. They did not show any activity on photosystem I or mitochondrial complex I, or generate toxic oxygen radicals by redox cycling reactions. Only moderate activity was found against mitochondrial complex III from plants, in contrast to much higher corresponding activity using an insect enzyme. PMID:11975168

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

    PubMed

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

    2014-08-01

    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

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

    PubMed Central

    Bergeron, François; Houde, Daniel; Hunting, Darel J.; Wagner, J. Richard

    2004-01-01

    2-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 complementary strand opposite the MQ moiety. For sequences with an internal MQ, the formation of cross-links with A and C opposite the MQ moiety was 2- to 3-fold greater than that with G and T. The yield of cross-links was more than 10-fold greater than that of breaks opposite MQ, which in turn was more than 2-fold greater than breaks at GG doublets. The yield of damage at GG doublets greatly increased for a sequence with a terminal MQ. The distribution of base damage was measured by enzymatic digestion and HPLC analysis (dAdo > dThd > dGuo > dCyd). The formation of novel products in MQ–DNA duplexes was attributed to the ability of excited MQ to generate the radical cations of all four DNA bases; thus, this photochemical reaction provides an ideal model system to study the effects of ionizing radiation and one-electron oxidants. PMID:15585661

  9. Naphthoquinone-mediated Inhibition of Lysine Acetyltransferase KAT3B/p300, Basis for Non-toxic Inhibitor Synthesis*

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2014-10-01

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

  11. Flow Injection Analysis Coupled with Carbon Electrodes as the Tool for Analysis of Naphthoquinones with Respect to Their Content and Functions in Biological Samples

    PubMed Central

    Babula, Petr; Huska, Dalibor; Hanustiak, Pavel; Baloun, Jiri; Krizkova, Sona; Adam, Vojtech; Hubalek, Jaromir; Havel, Ladislav; Zemlicka, Milan; Horna, Ales; Beklova, Miroslava; Kizek, Rene

    2006-01-01

    Naphthoquinones are one of the groups of secondary metabolites widespread in nature, where they mostly appear as chromatic pigments. They embody broad-range of biological actions from phytotoxic to fungicidal. An anticancer effect of naphthoquinones stimulates an interest in determination and characterization of single derivatives of 1,2- and 1,4-quinones in biological samples. The main aim of this work was to suggest a technique suitable to determine lawsone, juglone and/or plumbagin in biological samples and to study of their influence on BY-2 tobacco cells. The BY-2 tobacco cells were cultivated in the presence of the naphthoquinones of interest (500 ?g.l-1) for 24 h and then the morphological changes were observed. We found out that naphthoquinones triggered the programmed cell death at BY-2 cells, which can be confirmed by the apoptotic bodies in nucleus. After that we suggested and optimized different electrochemical techniques such differential pulse voltammetry (DPV) coupled with hanging mercury drop (HMDE) and carbon paste electrode, micro flow device coupled with carbon screen printed electrodes and flow injection analysis coupled with Coulochem III detector to determine them. The detection limits of naphthoquinones of interest were expressed as 3S/N and varied from units to hundreds of ng per millilitres according to methods used. Moreover, we utilized DPV coupled with HMDE and micro flow device to determine content of juglone in leaves Persian walnut (Juglans regia). We determined that the leaves contained juglone tenths of g per 100 g of fresh weight. The results obtained show the convincing possibilities of using of these methods in analysis of plant secondary metabolites.

  12. Anti-proliferative actions of 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone in vascular smooth muscle cells

    SciTech Connect

    Lee, Jung-Jin [Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of) [Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of); Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Zhang, Wei-Yun; Yi, Hyoseok; Kim, Yohan; Kim, In-Su [Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of)] [Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of); Shen, Gui-Nan; Song, Gyu-Yong [Department of Medicinal Chemistry, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of)] [Department of Medicinal Chemistry, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of); Myung, Chang-Seon, E-mail: cm8r@cnu.ac.kr [Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of) [Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of); Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

    2011-07-22

    Highlights: {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced VSMC proliferation in a dose-dependent manner with no apparent cytotoxicity. {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced phosphorylation of Erk1/2 and PLC{gamma}1. {yields} 2-Decylamino-DMNQ arrested a G{sub 0}/G{sub 1} cell cycle progression in association with pRb phosphorylation and PCNA expression. {yields} Both U0126, an Erk inhibitor, and U73122, a PLC{gamma} inhibitor, arrested a G{sub 0}/G{sub 1} phase of the cell cycle. -- Abstract: Naphthoquinone derivatives have been reported to possess various pharmacological activities, such as antiplatelet, anticancer, antifungal, and antiviral properties. In this study, we investigated the effects of a newly-synthesized naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2-decylamino-DMNQ), on VSMC proliferation and examined the molecular basis of the underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2-decylamino-DMNQ did not affect PDGF-R{beta} or Akt, it did inhibit the phosphorylation of Erk1/2 and PLC{gamma}1 induced by PDGF. Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G{sub 0}/G{sub 1} phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that both U0126, an Erk1/2 inhibitor, and U73122, a PLC{gamma} inhibitor, increased the proportion of cells in the G{sub 0}/G{sub 1} phase of the cell cycle. Thus, these results suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC proliferation and the mechanism of this action is through cell cycle arrest at the G{sub 0}/G{sub 1} phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation.

  13. Oxidation of 1-acyl-2-naphthol oximes: peri- and o-cyclisation and spiro cyclodimerisation of naphthoquinone nitrosomethide intermediates

    Microsoft Academic Search

    Paraskevi Supsana; Petros G Tsoungas; André Aubry; Stavroula Skoulika; George Varvounis

    2001-01-01

    The oxidation of 2-hydroxynaphthaldehyde oxime with lead(IV) acetate (LTA) gave a mixture of naphtho[1,8-de][1,2]oxazine and a spiro dimer. LTA oxidation of 6-bromo (or nitro)-2-hydroxynaphthaldehyde oximes provided only spiro dimers. Similar treatment of (2-hydroxy-1-naphthyl)keto oximes with LTA gave naphtho[1,8-de][1,2]oxazines and benzo[cd]indol-3(1H)-ones. Low temperature oxidation of 1-(2-hydroxy-1-naphthyl)propan-1-one oxime furnished 2-ethylbenzo[cd]indol-3(1H)-one and 1-ethylnaphtho[1,2-d]isoxazole-2-oxide. peri- and o-Naphthoquinone nitrosomethides are invoked as intermediates that undergo

  14. Effects of plant-derived naphthoquinones on the growth of Pleurotus sajor-caju and degradation of the compounds by fungal cultures.

    PubMed

    Curreli, N; Sollai, F; Massa, L; Comandini, O; Rufo, A; Sanjust, E; Rinaldi, A; Rinaldi, A C

    2001-01-01

    The growth of the white-rot basidiomycete Pleurotus sajor-caju in malt-agar plates was inhibited by three naturally occurring, plant-derived naphthoquinones: juglone, lawsone, and plumbagin. The latter two compounds exerted the most potent antifungal activity, and lawsone killed the mycelium at concentrations higher than 200 ppm. Plates containing juglone and lawsone presented large decolorized areas extending from area of fungal growth, suggesting an extracellular enzymatic degradation of these quinones. Screening of culture plates for extracellular enzymatic activities revealed the presence of both laccase and veratryl alcohol oxidase in most plates, the diffusion of both enzymes matching the decolorized area. In agitated cultures, the presence of juglone was found to stimulate the production of veratryl alcohol oxidase in a significant manner. This is the first time degradation of plant derived naphthoquinones by a white-rot fungus is reported. PMID:11688211

  15. The visible absorbance maximum of 2-hydroxy-1,4-naphthoquinone as a novel probe for the hydrogen bond donor abilities of solvents and solvent mixtures

    Microsoft Academic Search

    K. A. Idriss; H. Sedaira; E. Y. Hashem; M. S. Saleh; S. A. Soliman

    1996-01-01

    The electronic absorption spectra of 2-hydroxy-1,4-naphthoquinone (HNQ) in one- and two-component solvents are discussed. The visible absorption of this reagent has been shown to arise from a charge-transfer transition of the zwitterionic tautomer stabilized by a hydrogen bond donating solvent. The formation constant of the 1:1 hydrogen bonded complex with methanol, ethanol, andn-propanol has been determined at 25 °C from

  16. Evidence for redox cycling of lawsone (2-hydroxy-1,4-naphthoquinone) in the presence of the hypoxanthine/xanthine oxidase system.

    PubMed

    Osman, A M; van Noort, P C M

    2003-01-01

    This study reports that lawsone (2-hydroxy-1,4-naphthoquinone) undergoes redox cycling in the presence of the hypoxanthine/xanthine oxidase system. The rate of cytochrome c reduction obtained in the presence of 80 microM lawsone was almost three times the rate of cytochrome c reduction measured in its absence. This increase in the rate of cytochrome c reduction was partially inhibited by superoxide dismutase, suggesting the involvement of O(2)(.-) in this process. It is remarkable to note that, even though lawsone is considered to be a non-redox-cycling quinone in vitro, this quinone was shown to be more toxic in vivo in rats than menadione, causing haemolytic anemia of an oxidative nature and renal damage. The view that this quinone is a non-redox-cycling quinone was based on the inability of one-electron-transferring flavoenzymes such as NADPH-cytochrome c reductase to reduce this naphthoquinone. Our finding that lawsone, like menadione, undergoes redox cycling in the presence of the hypoxanthine/xanthine oxidase system could explain the observed oxidative damage of tissues inflicted by this quinone in rats in vivo. Such an observation therefore reconciles the in vivo toxicity results of this naphthoquinone with those of in vitro experiments. PMID:12884402

  17. 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

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

    2006-09-14

    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

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

    NASA Astrophysics Data System (ADS)

    Ashour, Safwan; Bayram, Roula

    2012-12-01

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

  19. Spectrophotometric determination of dapsone in pharmaceutical products using sodium 1,2-naphthoquinone-4-sulfonic as the chromogenic reagent.

    PubMed

    Wang, Huai You; Xu, Li Xiao; Xiao, Yan; Han, Juan

    2004-10-01

    Spectrophotometric determination of dapsone is described. The dapsone reacts with sodium 1,2-naphthoquinone-4-sulfonic in pH 6.98 buffer solution to form a salmon pink compound, and its maximum absorption wavelength is at 525 nm, epsilon525=3.68 x 10(4) l mol(-1) cm(-1). The absorbance of dapsone from 0.40 to 10 microg ml(-1) obeys Beer's law. The linear regression equation of the calibration graph is C=0.2334 A + 0.01288, with a linear regression correlation coefficient of 0.9998, the detection limit is 0.24 microg ml(-1), and recovery is from 99.2 to 102.4%. Effects of pH, surfactant, organic solvents, foreign ions, and standing time on the determination of dapsone have been examined. This method is simple and can be used for the determination of dapsone in injection solution of dapsone. The results obtained by this method agreed with those by the official method (dead-stop titration method [The Chinese Pharmacopoeia, Pharmacopoeia Commission, Ministry of Health, vol. 2, fifth ed., PRC Chemical Industry Press, Beijing, 2000, p.720]). PMID:15350932

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

    PubMed Central

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

    2008-01-01

    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. PMID:18408044

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

    PubMed Central

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

    2013-01-01

    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. PMID:23116403

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

  3. Addition of thiols to o-quinone methide: new 2-hydroxy-3-phenylsulfanylmethyl[1,4]naphthoquinones and their activity against the human malaria parasite Plasmodium falciparum (3D7).

    PubMed

    Sharma, Abhinay; Santos, Isabela O; Gaur, Pratibha; Ferreira, Vitor F; Garcia, Celia R S; da Rocha, David R

    2013-01-01

    A series of 36 new phenylsulfanylmethyl[1,4]naphthoquinones (7-42) were synthesized by a three-component reaction that involves lawsone, the appropriate aldehyde and thiols with variable substitution patterns. These reactions involve the in situ generation of o-quinone methides (o-QM) via Knoevenagel condensation and 1,4-nucleophilic addition under conventional heating or microwave irradiation. The new naphthoquinones obtained by this methodology were shown to have moderate to good in vitro antimalarial activity against Plasmodium falciparum (3D7). PMID:23202850

  4. Potential of 2-Hydroxy-3-Phenylsulfanylmethyl-[1,4]-Naphthoquinones against Leishmania (L.) infantum: Biological Activity and Structure-Activity Relationships

    PubMed Central

    Schmidt, Thomas J.; Borborema, Samanta E. T.; Ferreira, Vitor F.; Rocha, David R.; Tempone, Andre G.

    2014-01-01

    Naphtoquinones have been used as promising scaffolds for drug design studies against protozoan parasites. Considering the highly toxic and limited therapeutic arsenal, the global negligence with tropical diseases and the elevated prevalence of co-morbidities especially in developing countries, the parasitic diseases caused by various Leishmania species (leishmaniasis) became a significant public health threat in 98 countries. The aim of this work was the evaluation of antileishmanial in vitro potential of thirty-six 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones obtained by a three component reaction of lawsone, the appropriate aldehyde and thiols adequately substituted, exploiting the in situ generation of o-quinonemethides (o-QM) via the Knoevenagel condensation. The antileishmanial activity of the naphthoquinone derivatives was evaluated against promastigotes and intracellular amastigotes of Leishmania (Leishmania) infantum and their cytotoxicity was verified in mammalian cells. Among the thirty-six compounds, twenty-seven were effective against promastigotes, with IC50 values ranging from 8 to 189 µM; fourteen compounds eliminated the intracellular amastigotes, with IC50 values ranging from 12 to 65 µM. The compounds containing the phenyl groups at R1 and R2 and with the fluorine substituent at the phenyl ring at R2, rendered the most promising activity, demonstrating a selectivity index higher than 15 against amastigotes. A QSAR (quantitative structure activity relationship) analysis yielded insights into general structural requirements for activity of most compounds in the series. Considering the in vitro antileishmanial potential of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones and their structure-activity relationships, novel lead candidates could be exploited in future drug design studies for leishmaniasis. PMID:25171058

  5. Expedient synthesis of 3-hydroxyisoquinolines and 2-hydroxy-1,4-naphthoquinones via one-pot aryne acyl-alkylation/condensation.

    PubMed

    Allan, Kevin M; Hong, Boram D; Stoltz, Brian M

    2009-12-01

    A convenient method is disclosed for the synthesis of both 3-hydroxyisoquinolines and 2-hydroxy-1,4-naphthoquinones from beta-ketoesters using a one-pot aryne acyl-alkylation/condensation procedure. When performed in conjunction with a one-step method for the synthesis of the beta-ketoester substrates, this method provides a new route to these polyaromatic structures in only two steps from commercially available carboxylic acid starting materials. The utility of this approach is demonstrated in the synthesis of the atropisomeric P,N-ligand, QUINAP. PMID:19907787

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

    PubMed

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

    2012-01-01

    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

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

    PubMed Central

    2012-01-01

    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

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

    PubMed

    Kirkland, David; Marzin, Daniel

    2003-06-01

    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 mutations in Drosophila melanogaster. However, a small increase in micronucleus frequency was reported in the bone marrow of mice at a single mid-range dose level, 24h after intraperitoneal injection. In view of the wide use of Henna hair dyes it was deemed necessary to conduct a thorough investigation, under Good Laboratory Practice conditions, of the genotoxicity of HNQ. HNQ was non-mutagenic in bacterial (Ames test) or mammalian (V79 hprt) assays. It was borderline positive in a mouse lymphoma tk mutation assay and a chromosome aberration test (CHO cells), results that may reflect a similar clastogenic mechanism. Negative in vivo genotoxicity results were noted in the rat hepatocyte in vivo/in vitro UDS test, in peripheral lymphocytes (chromosome aberrations) of rats receiving repeated oral doses of HNQ at the MTD for 28 days, and in mouse and hamster bone marrow chromosome aberration tests. However small, but statistically significant increases in the incidence of bone marrow micronuclei were observed in two out of five tests at 72 h after dosing, but not at 24 or 48 h. There was evidence of haematotoxicity at 72 h, which may have been enhanced by the vehicle (DMSO) used in the positive tests. As erythropoiesis and administration of haematotoxic agents are known to induce small increases in the frequency of bone marrow micronuclei, typically at delayed sampling times, the data suggest that the positive 72 h response produced by HNQ is consistent with stimulation of haematopoiesis subsequent to haematological toxicity of HNQ, and not due to a DNA-reactive mechanism. Overall, the weight of evidence suggests that Henna and HNQ pose no genotoxic risk to the consumer. PMID:12787822

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

    PubMed Central

    2013-01-01

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

  10. Micelles catalyzed chemoselective synthesis 'in water' and biological evaluation of oxygen containing hetero-1,4-naphthoquinones as potential antifungal agents.

    PubMed

    Tandon, Vishnu K; Maurya, Hardesh K; Mishra, Nripendra N; Shukla, Praveen K

    2011-11-01

    Various oxygen containing 1,4-naphthoquinone derivatives have been synthesized chemoselectively by an economical, viable green methodology approach using water as solvent with or without surfactants such as Triton X-100, SDS, LD (laundry detergent), and TBAB, a phase transfer catalyst and evaluated for their in vitro antifungal and antibacterial activity. The antifungal profile of 3, 4a, 4b, and 6 indicated that compounds 3a, 3b, 4b, 6a, and 6c have potent antifungal activity compared to clinically prevalent antifungal drugs Fluconazole and Amphotericin-B against Sporothrix schenckii, Trichophyton mentagraphytes, and Candida parapsilosis and compound 3b has been found to be a lead antifungal agent for further study. PMID:21930375

  11. 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

    Daniel Marzin; David Kirkland

    2004-01-01

    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

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

    SciTech Connect

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

    1989-07-01

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

  13. Spectrophotometric study for the reaction between fluvoxamine and 1,2-naphthoquinone-4-sulphonate: Kinetic, mechanism and use for determination of fluvoxamine in its dosage forms

    NASA Astrophysics Data System (ADS)

    Darwish, Ibrahim A.; Abdine, Heba H.; Amer, Sawsan M.; Al-Rayes, Lama I.

    2009-05-01

    Spectrophotometric study was carried out, for the first time, to investigate the reaction between the antidepressant fluvoxamine (FXM) and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 9), an orange-colored product exhibiting maximum absorption peak ( ?max) at 470 nm was produced. The kinetics of the reaction was investigated and its activation energy was found to be 2.65 kcal mol -1. Because of this low activation energy, the reaction proceeded easily. The stoichiometry of the reaction was determined and the reaction mechanism was postulated. This color-developing reaction was successfully employed in the development of simple and rapid spectrophotometric method for determination of FXM in its pharmaceutical dosage forms. Under the optimized reaction conditions, Beer's law correlating the absorbance ( A) with FXM concentration ( C) was obeyed in the range of 0.6-8 ?g ml -1. The regression equation for the calibration data was A = 0.0086 + 0.1348 C, with good correlation coefficient (0.9996). The molar absorptivity ( ?) was 5.9 × 10 4 l mol -1 cm -1. The limits of detection and quantification were 0.2 and 0.6 ?g ml -1, respectively. The precision of the method was satisfactory; the values of relative standard deviations did not exceed 2%. The proposed method was successfully applied to the determination of FXM in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 100.47 ± 0.96%. The results obtained by the proposed method were comparable with those obtained by the official method. The proposed method is superior to all the previously reported spectrophotometric methods for determination of FXM in terms of its simplicity and sensitivity. The method is practical and valuable for its routine application in quality control laboratories for analysis of FXM.

  14. 'On water' assisted synthesis and biological evaluation of nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents.

    PubMed

    Tandon, Vishnu K; Maurya, Hardesh K; Verma, Manoj K; Kumar, Rohitashw; Shukla, Praveen K

    2010-06-01

    2-chloro-3-(4-methylpiperazin-1-yl)naphthalene-1,4-dione (3a), 2-chloro-3-(pyrrolidin-1-yl)naphthalene-1,4-dione (3b), 2-chloro-3-(piperidin-1-yl)naphthalene-1,4-dione (3c), 2-chloro-3-morpholinonaphthalene-1,4-dione (3d), 2-chloro-3-(2-phenylhydrazinyl)naphthalene-1,4-dione (3e), 2-(allylamino)-3-chloronaphthalene-1,4-dione (3f), 2-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-ylthio)acetic acid (3g), 2-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-ylthio)succinic acid (3h), methyl 2-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-ylthio)acetate (3i), 2-chloro-3-(2-mercaptoethylthio)naphthalene-1,4-dione (3j), 3-hydroxy-4-methyl-4H-naphtho[2,3-b][1,4]thiazine-5,10-dione (3k) and compounds 3l-q have been synthesized by a green methodology approach using water as solvent and evaluated for their antifungal and antibacterial activity. The antifungal profile of 3a-n indicated that compounds 3a-d, 3j, 3e and 3k have potent antifungal activity. Amongst the most promising antifungal compounds, 3a-g, 3j, 3k showed better antifungal activity than clinically prevalent antifungal drugs Fluconazole and Amphotericin-B against Trichophyton mentagraphytes and compounds 3j and 3k have been found to be lead antifungal bicyclic and tricyclic 1,4-naphthoquinones. Compound 3k also exhibited pronounced antibacterial activity. PMID:20207052

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

    PubMed

    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; Salomão, Kelly; Silva, Cristiane F; Silva, Patricia B; Soeiro, Maria de Nazaré C

    2011-01-01

    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. PMID:22091400

  16. 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

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

    2014-05-01

    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

  17. Effects of ethanolic extract and naphthoquinones obtained from the bulbs of Cipura paludosa on short-term and long-term memory: involvement of adenosine A? and A?A receptors.

    PubMed

    Lucena, Greice M R S; Matheus, Filipe C; Ferreira, Vania M; Tessele, Priscila B; Azevedo, Mariangela S; Cechinel-Filho, Valdir; Prediger, Rui D

    2013-04-01

    Previous studies from our group have indicated important biological properties of the ethanolic extract and isolated compounds from the bulbs of Cipura paludosa (Iridaceae), a native plant widely distributed in northern Brazil, including antioxidant, neuroprotective and anti-nociceptive activities. In the present study, the effects of the ethanolic extract and its two naphthoquinones (eleutherine and isoeleutherine) on the short- and long-term memory of adult rodents were assessed in social recognition and inhibitory avoidance tasks. Acute pre-training oral administration of the ethanolic extract improved the short-term social memory in rats as well as facilitated the step-down inhibitory avoidance short- and long-term memory in mice. Moreover, the co-administration of 'non-effective' doses of the extract of Cipura paludosa and the adenosine receptor antagonists caffeine (non-selective), DPCPX (adenosine A1 receptor antagonist) and ZM241385 (adenosine A2A receptor antagonist) improved the social recognition memory of rats. In the inhibitory avoidance task, the co-administration of sub-effective doses of the extract with caffeine or ZM241385, but not with DPCPX, improved the short- and long-term memory of mice. Finally, the acute oral administration of eleutherine and isoeleutherine facilitated the inhibitory avoidance short- and long-term memory in mice. These results demonstrate for the first time the cognitive-enhancing properties of the extract and isolated compounds from the bulbs of Cipura paludosa in rodents and suggest a possible involvement of adenosine A1 and A2A receptors in these effects. PMID:23057724

  18. Charge–transfer reaction of 2,3-dichloro-1,4-naphthoquinone with crizotinib: Spectrophotometric study, computational molecular modeling and use in development of microwell assay for crizotinib

    PubMed Central

    Alzoman, Nourah Z.; Alshehri, Jamilah M.; Darwish, Ibrahim A.; Khalil, Nasr Y.; Abdel-Rahman, Hamdy M.

    2014-01-01

    The reaction of 2,3-dichloro-1,4-naphthoquinone (DCNQ) with crizotinib (CZT; a novel drug used for treatment of non-small cell lung cancer) was investigated in different solvents of varying dielectric constants and polarity indexes. The reaction produced a red-colored product. Spectrophotometric investigations confirmed that the reaction proceeded through charge–transfer (CT) complex formation. The molar absorptivity of the complex was found to be linearly correlated with the dielectric constant and polarity index of the solvent; the correlation coefficients were 0.9567 and 0.9069, respectively. The stoichiometric ratio of DCNQ:CZT was found to be 2:1 and the association constant of the complex was found to be 1.07 × 102 l/mol. The kinetics of the reaction was studied; the order of the reaction, rate and rate constant were determined. Computational molecular modeling for the complex between DCNQ and CZT was conducted, the sites of interaction on CZT molecule were determined, and the mechanism of the reaction was postulated. The reaction was employed as a basis in the development of a novel 96-microwell assay for CZT in a linear range of 4–500 ?g/ml. The assay limits of detection and quantitation were 2.06 and 6.23 ?g/ml, respectively. The assay was validated as per the guidelines of the International Conference on Harmonization (ICH) and successfully applied to the analysis of CZT in its bulk and capsules with good accuracy and precision. The assay has high throughput and consumes a minimum volume of organic solvents thus it reduces the exposures of the analysts to the toxic effects of organic solvents, and significantly reduces the analysis cost. PMID:25685046

  19. 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 Central

    2013-01-01

    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

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

    PubMed Central

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

    2012-01-01

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

  1. 2-Hydroxy-1,4-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.

    PubMed

    Marzin, Daniel; Kirkland, David

    2004-05-01

    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 bone marrow micronucleus test in male and female NMRI BRL/BR mice at oral doses of 75, 150 and 300mg/kg in two vehicles (DMSO and 0.5% aqueous MC), evaluated micronuclei at 24, 48 and 72h, plasma levels of HNQ at 0.5, 1 and 4h, and haematology parameters at 72h after administration. The mechanism of in vitro clastogenic activity of HNQ was investigated by evaluation of the potential of HNQ to produce oxidative DNA damage after treatment of CHO with 10mM HNQ, followed by quantification of DNA fragments using the comet assay. In the micronucleus test, HNQ at 300mg/kg produced mortality and clinical signs at similar incidence and severity for both vehicles. Levels of HNQ in the plasma of treated mice were dose-related, of similar magnitude for both vehicles, but higher in females than in males. Maximum concentrations were found at 0.5 or 1h. At 300mg/kg, HNQ slightly affected RBC parameters suggesting haematotoxicity. No increase in the frequency of micronuclei was observed for any dose, vehicle or time point, whereas the positive control substance (CPA) produced a clear positive response. No evidence of HNQ-induced oxidative DNA damage was found at clastogenic concentrations in vitro, whereas the positive control substance (H(2)O(2)) produced a clear increase. In conclusion, HNQ was negative for induction of bone marrow micronuclei in mice up to 72h after administration in two different vehicles, and its in vitro clastogenicity was not due to oxidative damage. These results confirm that HNQ poses no or negligible genotoxic risk. PMID:15099823

  2. New naphthoquinone derivatives against glioma cells.

    PubMed

    Redaelli, Marco; Mucignat-Caretta, Carla; Isse, Abdirisak Ahmed; Gennaro, Armando; Pezzani, Raffaele; Pasquale, Riccardo; Pavan, Valeria; Crisma, Marco; Ribaudo, Giovanni; Zagotto, Giuseppe

    2015-05-26

    This work was aimed to the development of a set of new naphtoquinone derivatives that can act against glioma. The compounds were tested in order to find out their ability to inhibit the growth of glioma cells, and the results of these assays were correlated with electrochemical analysis and NMR-based reoxidation kinetic studies, suggesting that a redox mechanism underlies and may explain the observed biological behavior. In addition to a full description of the synthetic pathways, electrochemistry, NMR and single crystal X-ray diffraction data are provided. PMID:25916907

  3. Hydroxylated naphthoquinones as substrates for Escherichia coli anaerobic reductases.

    PubMed Central

    Rothery, R A; Chatterjee, I; Kiema, G; McDermott, M T; Weiner, J H

    1998-01-01

    We have used two hydroxylated naphthoquinol menaquinol analogues, reduced plumbagin (PBH2, 5-hydroxy-2-methyl-1,4-naphthoquinol) and reduced lapachol [LPCH2, 2-hydroxy-3-(3-methyl-2-butenyl)-1, 4-naphthoquinol], as substrates for Escherichia coli anaerobic reductases. These compounds have optical, solubility and redox properties that make them suitable for use in studies of the enzymology of menaquinol oxidation. Oxidized plumbagin and oxidized lapachol have well resolved absorbances at 419 nm (epsilon=3.95 mM-1. cm-1) and 481 nm (epsilon=2.66 mM-1.cm-1) respectively (in Mops/KOH buffer, pH 7.0). PBH2 is a good substrate for nitrate reductase A (Km=282+/-28 microM, kcat=120+/-6 s-1) and fumarate reductase (Km=155+/-24 microM, kcat=30+/-2 s-1), but not for DMSO reductase. LPCH2 is a good substrate for nitrate reductase A (Km=57+/-35 microM, kcat=68+/-13 s-1), fumarate reductase (Km=85+/-27 microM, kcat=74+/-6 s-1) and DMSO reductase (Km=238+/-30 microM, kcat=191+/-21 s-1). The sensitivity of enzymic LPCH2 and PBH2 oxidation to 2-n-heptyl-4-hydroxyquinoline N-oxide inhibition is consistent with their oxidation occurring at sites of physiological quinol binding. PMID:9576848

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

    E-print Network

    Trumpower, Bernard L.

    of the cytochrome bc1 complex that bind to the ubiquinol oxidation site between cytochrome b and the iron circumvent the drug resistance. We previously developed the yeast and bovine bc1 complexes as surrogates found a group of compounds with alkyl side-chains that effectively inhibit the yeast bc1 complex

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

    Microsoft Academic Search

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

    2011-01-01

    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

  6. Naphthoquinones from Onosma paniculata Induce Cell-Cycle Arrest and Apoptosis in Melanoma Cells

    PubMed Central

    2012-01-01

    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

  7. Electrochemical properties of substituted 2-methyl-1,4-naphthoquinones: redox behavior predictions.

    PubMed

    Elhabiri, Mourad; Sidorov, Pavel; Cesar-Rodo, Elena; Marcou, Gilles; Lanfranchi, Don Antoine; Davioud-Charvet, Elisabeth; Horvath, Dragos; Varnek, Alexandre

    2015-02-16

    In the context of the investigation of drug-induced oxidative stress in parasitic cells, electrochemical properties of a focused library of polysubstituted menadione derivatives were studied by cyclic voltammetry. These values were used, together with compatible measurements from literature (quinones and related compounds), to build and evaluate a predictive structure-redox potential model (quantitative structure-property relationship, QSPR). Able to provide an online evaluation (through Web interface) of the oxidant character of quinones, the model is aimed to help chemists targeting their synthetic efforts towards analogues of desired redox properties. PMID:25556761

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

    PubMed

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

    2009-09-01

    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 epimastigotes. Here, we further investigated the activity and the mechanisms of action of these quinones. They exhibited powerful effects on intracellular amastigotes, presenting low toxicity to the host cells. Ultrastructural analyses of treated epimastigotes and trypomastigotes indicated a potent effect of the three naphthofuranquinones on the parasite mitochondrion, which appeared drastically swollen and with a washed-out matrix profile. Fluorescence-activated cell sorting analysis of rhodamine 123-stained T. cruzi showed that the three naphthofuranquinones caused a potent dose-dependent collapse of the mitochondrial membrane potential, especially in the epimastigote form. Naphthofuranquinones also decreased specifically mitochondrial complex I-III activity in both epimastigotes and trypomastigotes, parallel to a reduction in succinate-induced oxygen consumption. Mitochondrial hydrogen peroxide formation was also increased in epimastigotes after treatment with the naphthofuranquinones. Our results indicate that the trypanocidal action of the naphthofuranquinones is associated with mitochondrial dysfunction, leading to increased reactive oxygen species generation and parasite death. PMID:19501647

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

    E-print Network

    Stoltz, Brian M.

    -methoxy-2-(trimethylsilyl)phenyl triflate (Table 1, entry 1),1 4,5-dimethoxy-2-(trimethylsilyl)phenyl,5-difluoro-2-(trimethylsilyl)phenyl triflate (Table 1, entry 5),4 and 2-(trimethylsilyl)cyclohexene triflate

  10. Ytterbium-decreasing Streptomyces sp. and its naphthoquinone-pigment production in the presence of rare-earth elements

    Microsoft Academic Search

    Manjiroh Kamijo; Tohru Suzuki; Keiichi Kawai; Toshiaki Fujii; Hironobu Murase

    1999-01-01

    We screened for oligotrophic microorganisms capable of decreasing the concentration of ytterbium (Yb), a representative of the heavy rare-earth elements, in a culture medium. From 476 strains of oligotrophic microorganisms (grown on 1100 diluted nutrient agar) isolated from soil and river water samples, 5 strains capable of reducing the concentration of Yb in diluted nutrient broth containing 5 ppm Yb

  11. Reversed-phase HPLC determination of chlorophyll a' and naphthoquinones in photosystem I of red algae: existence of two menaquinone-4 molecules in photosystem I of Cyanidium caldarium.

    PubMed

    Yoshida, Emi; Nakamura, Akimasa; Watanabe, Tadashi

    2003-07-01

    Chlorophyll (Chl) a', the C13(2)-epimer of Chl a, is one of the two Chl molecules constituting the primary electron donor (P700) of photosystem (PS) I of a thermophilic cyanobacterium Synechococcus elongatus. To examine whether PS I of other oxygenic photosynthetic organisms in general contain one Chl a' molecule in P700, the pigment composition of thylakoid membranes and PS I preparations isolated from red algae Porphyridium purpureum and Cyanidium caldarium was examined by reversed-phase HPLC with particular attention to Chl a' and phylloquinone (PhQ), the secondary electron acceptor of PS I. The two red algae contained one Chl a' molecule at the core part of PS I. In PS I of C. caldarium, two menaquinone-4 (MQ-4) molecules were detected in place of PhQ used by higher plants and cyanobacteria. The 1:2:1 stoichiometry among Chl a', PhQ (MQ-4) and P700 in PS I of the red algae indicates that one Chl a' molecule universally exists in PS I of oxygenic photosynthetic organisms, and two MQ-4 molecules are associated with PS I of C. caldarium. PMID:12880082

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

    EPA Science Inventory

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

  13. Activity of 7-methyljuglone derivatives against Mycobacterium tuberculosis and as subversive substrates for mycothiol disulfide reductase

    Microsoft Academic Search

    Anita Mahapatra; Sannah P. N. Mativandlela; B. Binneman; P. B. Fourie; Chris J. Hamilton; J. J. M. Meyer; F. van der Kooy; Peter Houghton; Namrita Lall

    2007-01-01

    The naphthoquinone 7-methyljuglone (5-hydroxy-7-methyl-1,4-naphthoquinone) has previously been isolated and identified as an active component of root extracts of Euclea natalensis which displays antitubercular activity. Herein, a series of synthetic and plant-derived naphthoquinone derivates of the 7-methyljuglone scaffold have been prepared and evaluated for antibacterial activity against Mycobacterium tuberculosis. Several of these compounds have been shown to operate as subversive substrates

  14. Differential roles for menaquinone and demethylmenaquinone in anaerobic electron transport of E. coli and their fnr -independent expression

    Microsoft Academic Search

    Gottfried Unden; J. W. Goethe-Universitfit

    1988-01-01

    Escherichia coli grown with glucose in the absence of added electron acceptors contained 3–4 times more naphthoquinones (menaquinone plus demethylmenaquinone) than in the presence of O2. Presence of electron acceptors resulted in a slight additional increase of the naphthoquinone content. A strain defective in the fnr gene, which encodes the transcriptional activator of anaerobic respiration, showed the same response. With

  15. Cytotoxic properties of iron-hydroxynaphthoquinone complexes in rat hepatocytes.

    PubMed

    Kumbhar, A; Padhye, S; Ross, D

    1996-07-01

    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 toxic than the iron complexes of 2-OH-1,4 naphthoquinone (2-OH-1,4 NQ; Lawsone) indicating that the mechanisms of toxicity are different. Electrochemical studies on these complexes shows that 5-OH-1,4 NQ facilitates formation of stable semiquinone species while 2-OH-1,4 NQ does not. The low redox potential of 2-OH-1,4 NQ makes it a poor substrate for metabolism by reductases. PMID:8696075

  16. On the enigmatic scent glands of dyspnoan harvestmen (Arachnida, Opiliones): first evidence for the production of volatile secretions.

    PubMed

    Raspotnig, Günther; Schaider, Miriam; Stabentheiner, Edith; Leis, Hans-Jörg; Karaman, Ivo

    2014-01-01

    While considerable knowledge on the chemistry of the scent gland secretions from the opilionid suborders Laniatores and Cyphophthalmi has been compiled, it is the Palpatores (Eupnoi and Dyspnoi) where chemical data are scarce. In particular, the Dyspnoi have remained nearly unstudied, mainly due to their reported general reluctance to release secretions as well as to the phenomenon of production of insoluble-and inaccessible-solid secretion. We here show that at least certain nemastomatid Dyspnoi, namely all three species of genus Carinostoma, indeed produce a volatile secretion, comprising octan-3-one, 6-methyl-5-hepten-2-one and acetophenone in species-specific combinations. In all Carinostoma spp., these volatiles are embedded in a semi-volatile, naphthoquinone matrix (mainly 1,4-naphthoquinone and 6-methyl-1,4-naphthoquinone). In detail, acetophenone and traces of naphthoquinones characterize the secretions of Carinostoma carinatum. A mixture of octan-3-one, 6-methyl-5-hepten-2-one and large amounts of naphthoquinones were found in C. elegans, and 6-methyl-5-hepten-2-one together with small amounts of naphthoquinones in the secretions of C. ornatum. So far, exclusively naphthoquinones had been reported from a single dyspnoan hitherto studied, Paranemastoma quadripunctatum. PMID:24634568

  17. Cataractogenicity and bioactivation of naphthalene derivatives in lens culture and in vivo

    SciTech Connect

    Lubek, B.M.; Kubow, S.; Basu, P.K.; Wells, P.G. (Univ. of Toronto, Ontario (Canada))

    1989-01-01

    The cataractogenicity of naphthalene derivatives was investigated in a lens culture system that included the lens with an intact capsule and epithelium. The in vivo cataractogenicity of naphthalene, 1000 or 2000 mg/kg ip, also was evaluated in New Zealand white and Chinchilla pigmented rabbits. A dose-related brunescence was observed in lenses incubated with 1,4-naphthoquinone in concentrations from 31.6 to 316 microM. With 316 microM naphthoquinone, lenses were totally opaque within 24 hr. No lenticular opacities were observed with 1-naphthol or 2-naphthol in incubations lasting up to 96 hr. The bioactivation of naphthalene derivatives to reactive free radical intermediates by lenses in organ culture was investigated by electron spin resonance spectrometry (ESR) using the spin trap alpha-phenyl-N-t-butylnitrone (PBN). Lenses were incubated with 316 microM naphthoquinone and 100 mM PBN for 0.25, 4 or 7 hr. A spin trapped radical product with unresolved peaks was observed with 0.25 and 7 hr incubation. No radicals were detected in the 4 hr incubation, nor in control cultures lacking either the lens, naphthoquinone or PBN. In the in vivo studies, naphthalene was cataractogenic in both albino and pigmented rabbits. The in vitro results indicate that naphthoquinone can be bioactivated by rabbit lens to a reactive free radical intermediate, which may contribute to cataractogenicity.

  18. Biologically Active Metabolites Produced by the Basidiomycete Quambalaria cyanescens

    PubMed Central

    Stod?lková, Eva; Císa?ová, Ivana; Kola?ík, Miroslav; Chudí?ková, Milada; Novák, Petr; Man, Petr; Kuzma, Marek; Pavl?, Barbora; ?erný, Jan; Flieger, Miroslav

    2015-01-01

    Four strains of the fungus Quambalaria cyanescens (Basidiomycota: Microstromatales), were used for the determination of secondary metabolites production and their antimicrobial and biological activities. A new naphthoquinone named quambalarine A, (S)-(+)-3-(5-ethyl-tetrahydrofuran-2-yliden)-5,7,8-trihydroxy-2-oxo-1,4-naphthoquinone (1), together with two known naphthoquinones, 3-hexanoyl-2,5,7,8-tetrahydroxy-1,4-naphthoquinone (named here as quambalarine B, 2) and mompain, 2,5,7,8-tetrahydroxy-1,4-naphthoquinone (3) were isolated. Their structures were determined by single-crystal X-ray diffraction crystallography, NMR and MS spectrometry. Quambalarine A (1) had a broad antifungal and antibacterial activity and is able inhibit growth of human pathogenic fungus Aspergillus fumigatus and fungi co-occurring with Q. cyanescens in bark beetle galleries including insect pathogenic species Beauveria bassiana. Quambalarine B (2) was active against several fungi and mompain mainly against bacteria. The biological activity against human-derived cell lines was selective towards mitochondria (2 and 3); after long-term incubation with 2, mitochondria were undetectable using a mitochondrial probe. A similar effect on mitochondria was observed also for environmental competitors of Q. cyanescens from the genus Geosmithia. PMID:25723150

  19. Biologically active metabolites produced by the basidiomycete Quambalaria cyanescens.

    PubMed

    Stod?lková, Eva; Císa?ová, Ivana; Kola?ík, Miroslav; Chudí?ková, Milada; Novák, Petr; Man, Petr; Kuzma, Marek; Pavl?, Barbora; ?erný, Jan; Flieger, Miroslav

    2015-01-01

    Four strains of the fungus Quambalaria cyanescens (Basidiomycota: Microstromatales), were used for the determination of secondary metabolites production and their antimicrobial and biological activities. A new naphthoquinone named quambalarine A, (S)-(+)-3-(5-ethyl-tetrahydrofuran-2-yliden)-5,7,8-trihydroxy-2-oxo-1,4-naphthoquinone (1), together with two known naphthoquinones, 3-hexanoyl-2,5,7,8-tetrahydroxy-1,4-naphthoquinone (named here as quambalarine B, 2) and mompain, 2,5,7,8-tetrahydroxy-1,4-naphthoquinone (3) were isolated. Their structures were determined by single-crystal X-ray diffraction crystallography, NMR and MS spectrometry. Quambalarine A (1) had a broad antifungal and antibacterial activity and is able inhibit growth of human pathogenic fungus Aspergillus fumigatus and fungi co-occurring with Q. cyanescens in bark beetle galleries including insect pathogenic species Beauveria bassiana. Quambalarine B (2) was active against several fungi and mompain mainly against bacteria. The biological activity against human-derived cell lines was selective towards mitochondria (2 and 3); after long-term incubation with 2, mitochondria were undetectable using a mitochondrial probe. A similar effect on mitochondria was observed also for environmental competitors of Q. cyanescens from the genus Geosmithia. PMID:25723150

  20. Metabolism of naphthalene by Cunninghamella elegans.

    PubMed Central

    Cerniglia, C E; Gibson, D T

    1977-01-01

    Cunninghamella elegans grown on Sabouraud dextrose broth in the presence of naphthalene produced six metabolites. Each product was isolated and identified by conventional chemical techniques. The major metabolites were 1-naphthol (67.9%) and 4-hydroxy-1-tetralone (16.7%). Minor products isolated were 1,4-naphthoquinone (2.8%), 1,2-naphthoquinone (0.2%), 2-naphthol (6.3%), and trans-1,2-dihydroxy-1,2-dihydronaphthalene (5.3%). C. elegans oxidized both 1-naphthol and 1,4-naphthoquinone to 4-hydroxy-1-tetralone. The results suggest that C. elegans oxidizes naphthalene by a sequence of reactions similar to those reported for the mammalian metabolism of this hydrocarbon. PMID:921262

  1. Redox activity of naphthalene secondary organic aerosol

    NASA Astrophysics Data System (ADS)

    McWhinney, R. D.; Zhou, S.; Abbatt, J. P. D.

    2013-04-01

    Chamber secondary organic aerosol (SOA) from low-NOx photooxidation of naphthalene by hydroxyl radical was examined with respect to its redox cycling behaviour using the dithiothreitol (DTT) assay. Naphthalene SOA was highly redox active, consuming DTT at an average rate of 118 ± 14 pmol per minute per ?g of SOA material. Measured particle-phase masses of the major previously identified redox active products, 1,2- and 1,4-naphthoquinone, accounted for only 21 ± 3% of the observed redox cycling activity. The redox-active 5-hydroxy-1,4-naphthoquinone was identified as a new minor product of naphthalene oxidation, and including this species in redox activity predictions increased the predicted DTT reactivity to 30 ± 5% of observations. Similar attempts to predict redox behaviour of oxidised two-stroke engine exhaust particles by measuring 1,2-naphthoquinone, 1,4-naphthoquinone and 9,10-phenanthrenequinone predicted DTT decay rates only 4.9 ± 2.5% of those observed. Together, these results suggest that there are substantial unidentified redox-active SOA constituents beyond the small quinones that may be important toxic components of these particles. A gas-to-SOA particle partitioning coefficient was calculated to be (7.0 ± 2.5) × 10-4 m3 ?g-1 for 1,4-naphthoquinone at 25 °C. This value suggests that under typical warm conditions, 1,4-naphthoquinone is unlikely to contribute strongly to redox behaviour of ambient particles, although further work is needed to determine the potential impact under conditions such as low temperatures where partitioning to the particle is more favourable. As well, higher order oxidation products that likely account for a substantial fraction of the redox cycling capability of the naphthalene SOA are likely to partition much more strongly to the particle phase.

  2. Non-enzymatic oxidation of NADH by quinones

    NASA Astrophysics Data System (ADS)

    Scherbak, Nikolai; Strid, Åke; Eriksson, Leif A.

    2005-10-01

    Non-enzymatic oxidation of NADH by a large number of different quinones has been explored both theoretically and experimentally. It is concluded that the smaller benzo- and naphtho-quinones are capable of oxidising NADH in aqueous solution, whereas the larger anthraquinone is not. The mechanisms of stepwise electron and proton transfers are explored, and ruled out in favour of direct hydride transfer. For menadione (2-methyl-1,4-naphthoquinone), no reaction is observed experimentally; theoretically we find that there is a very close balance between the energetic cost of hydride removal from NADH and the energy gain of formation of the menadione semiquinone radical anion.

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

    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.

  4. Hydrogen Peroxide Formation in a Surrogate Lung Fluid by Transition Metals and Quinones Present in Particulate Matter

    PubMed Central

    2015-01-01

    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

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

    PubMed

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

    2014-06-17

    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

  6. 2-methylnaphthazarin 5- O-glucoside from the methanol extracts of in vitro cultures of Drosera species

    Microsoft Academic Search

    Jaromir Budzianowski

    1997-01-01

    The methanol extracts of Drosera rotundifolia and D. spathulata obtained by in vitro micropropagation yielded the new pigment 2-methylnaphthazarin (5,8-dihydroxy-2-methyl-1,4-naphthoquinone) 5-O-glucoside, which is an artefact formed from rossoliside (7-methylhydrojuglone 4-O-glucoside) during extraction with methanol.

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

    Microsoft Academic Search

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

    2004-01-01

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

  8. Vitamin K

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin K was identified in the early 1930’s when it was shown to be essential for normal blood coagulation. Phylloquinone (2-methyl-3-phytyl-1,4-naphthoquinone) found in green plants is the major source of the vitamin. Large amounts of menaquinones with lengthy side chains are also synthesized in...

  9. Reactivity of indanedioneketene dimer with amines.

    PubMed

    Malamidou-Xenikaki, Elizabeth; Spyroudis, Spyros; Tsanakopoulou, Maria; Krautscheid, Harald

    2007-01-19

    The highly reactive indanedioneketene 5, resulting from the thermal decomposition of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone, 4), in the absence of nucleophiles dimerizes to the corresponding tetraoxo spiro oxetanone 6 in quantitative yield. This oxetanone exhibits an interesting reactivity toward amines. PMID:17221967

  10. Protection or cytotoxicity mediated by a novel quinonoid-polyphenol compound?

    PubMed

    Milackova, Ivana; Rackova, Lucia; Majekova, Magdalena; Mrvova, Natasa; Stefek, Milan

    2015-01-01

    Many natural and synthetic quinones and naphthoquinones possess a variety of beneficial pharmacological properties. In plants, the cytotoxic properties of quinones serve in their defensive roles against invading bacteria, fungi and parasites. In this regard many quinones as well as polyphenols, exerting generally toxicity at high dosages, are able to induce favorable hormetic responses at a low dosage. The novel chloronaphthoquinone derivative of quercetin (CHNQ) showed a profound cytotoxicity followed by enhancement of intracellular generation of oxidants in human neonatal B-HNF-3 fibroblasts. Its synthetic precursors, quercetin and 2-chloro-3-hydroxy-[1,4]naphthoquinone, failed to induce these effects, and paradoxically, only CHNQ at a low concentration provided partial protection of the cells against oxidative challenge. Thus, the novel quinonoid-polyphenol CHNQ might have a merit in the search for new prospective agents in prevention and management of ageing and ageing-related pathologies. PMID:25367759

  11. Problem of sludge formation in solar oil

    SciTech Connect

    Chechel, P.S.; Mikhno, S.I.; Voitkovskii, B.F.; Epimakho, M.N.

    1982-01-01

    The problem of sludge from thermal polymerization and oxidation in solar wash oil used for the recovery of benzol hydrocarbons from coke oven gas was investigated. To determine the temperature dependence of the sludge formation, batches of solar oil were held at 20, 80, 120, and 140/sup 0/C for 24 hours. Included in the discussion was the use of 1,2-naphthoquinone as an additive to suppress sludge formation. Also, the operation and steam consumption of the benzol hydrocarbon distillation column was discussed. It was concluded that changing the operating regime of the still and adding 1,2-naphthoquinone to the return solar oil decreased significantly the sludge formation, while the steam consumption remained constant.

  12. Quinone-enhanced reduction of nitric oxide by xanthine/xanthine oxidase.

    PubMed

    Sanchez-Cruz, Pedro; Alegría, Antonio E

    2009-05-01

    The quinones 1,4-naphthoquinone, methyl-1,4-naphthoquinone, tetramethyl-1,4-benzoquinone, 2,3-dimethoxy-5-methyl-1,4-benzoquinone, 2,6-dimethylbenzoquinone, 2,6-dimethoxybenzoquinone, and 9,10-phenanthraquinone enhance the rate of nitric oxide reduction by xanthine/xanthine oxidase in nitrogen-saturated phosphate buffer (pH 7.4). Maximum initial rates of NO reduction (V(max)) and the amount of nitrous oxide produced after 5 min of reaction increase with quinone one- and two-electron redox potentials measured in acetonitrile. One of the most active quinones of those studied is 9,10-phenanthraquinone with a V(max) value 10 times larger than that corresponding to the absence of quinone, under the conditions of this work. Because NO production is enhanced under hypoxia and under certain pathological conditions, the observations obtained in this work are very relevant to such conditions. PMID:19301825

  13. In vitro combinatory antimicrobial effect of plumbagin with oxacillin and tetracycline against Staphylococcus aureus.

    PubMed

    Rondevaldova, Johana; Novy, Pavel; Kokoska, Ladislav

    2015-01-01

    Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a bicyclic naphthoquinone naturally distributed among Plumbago species, has been reported to have antimicrobial activity against a wide range of microorganisms. In this study, plumbagin was examined for its combinatory antimicrobial effect with tetracycline or oxacillin against nine strains of Staphylococcus aureus, including its methicillin- and multidrug-resistant strains. Minimum inhibitory concentrations were determined through the broth microdilution method, whereas the combinatory effect was evaluated according to the sum of fractional inhibitory concentration (?FIC) indices. Additive interactions were obtained for both combinations against most of the strains tested. Synergy was obtained for combination with oxacillin against two out of seven strains (?FIC range 0.273-0.281), both were methicillin resistant. Our results proved plumbagin as a compound suitable for anti-Staphylococcal combinatory testing. Moreover, to the best of our knowledge, this is the first report of plumbagin synergy with oxacillin against S. aureus strains, including its resistant forms. PMID:25266704

  14. Quinone-Enhanced Reduction of Nitric Oxide by Xanthine/Xanthine Oxidase

    PubMed Central

    Sanchez-Cruz, Pedro; Alegría, Antonio E.

    2009-01-01

    The quinones 1,4-naphthoquinone, methyl-1,4-naphthoquinone, tetramethyl-1,4-benzoquinone, 2,3-dimethoxy-5-methyl-1,4-benzoquinone, 2,6-dimethylbenzoquinone, 2,6-dimethoxybenzoquinone, and 9,10-phenanthraquinone enhance the rate of nitric oxide reduction by xanthine/xanthine oxidase in nitrogen-saturated phosphate buffer (pH 7.4). Maximum initial rates of NO reduction (Vmax) and the amount of nitrous oxide produced after 5 min of reaction increase with quinone one- and two-electron redox potentials measured in acetonitrile. One of the most active quinones of those studied is 9,10-phenanthraquinone with a Vmax value 10 times larger than that corresponding to the absence of quinone, under the conditions of this work. Because NO production is enhanced under hypoxia and under certain pathological conditions, the observations obtained in this work are very relevant to such conditions. PMID:19301825

  15. Bioactive constituents of brazilian red propolis.

    PubMed

    Trusheva, Boryana; Popova, Milena; Bankova, Vassya; Simova, Svetlana; Marcucci, Maria Cristina; Miorin, Patricia Laguna; da Rocha Pasin, Flavia; Tsvetkova, Iva

    2006-06-01

    In a new propolis type, red Brazilian propolis, 14 compounds were identified (six of them new for propolis), among them simple phenolics, triterepenoids, isoflavonoids, prenylated benzophenones and a naphthoquinone epoxide (isolated for the first time from a natural source). Three of the major components demonstrated significant antimicrobial activity, and two (obtained as inseparable mixture) possessed radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH). PMID:16786055

  16. Bioactive Constituents of Brazilian Red Propolis

    Microsoft Academic Search

    Boryana Trusheva; Milena Popova; Vassya Bankova; Svetlana Simova; Maria Cristina Marcucci; Patricia Laguna Miorin; Flavia da Rocha Pasin; Iva Tsvetkova; Rua Maria Candida; Vila Guilherme

    2006-01-01

    In a new propolis type, red Brazilian propolis, 14 compounds were identified (six of them new for propolis), among them simple phenolics, triterepenoids, isoflavonoids, prenylated benzophenones and a naphthoquinone epoxide (isolated for the first time from a natural source). Three of the major components demonstrated significant antimicrobial activity, and two (obtained as inseparable mixture) possessed radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl

  17. The allelopathic effects of juglone and walnut leaf extracts on yield, growth, chemical and PNE compositions of strawberry cv. Fern

    Microsoft Academic Search

    S. Ercisli; A. Esitken; E. Orhan

    2005-01-01

    Allelopathic effects of juglone and walnut leaf extracts from Persian walnut ( Juglans regia L.) on yield, growth, chemi- cal and plant nutrient element composition of the day-neutral strawberry (Fragaria × ananassa L.) cultivar Fern were investigated as part of an effort to identify tolerant species to plant adjacent to walnut. Strawberry plants were treated with juglone (5-hydroxy-1.4 naphthoquinone, 1mM)

  18. The specific functions of menaquinone and demethylmenaquinone in anaerobic respiration with fumarate, dimethylsulfoxide, trimethylamine N-oxide and nitrate by Escherichia coli

    Microsoft Academic Search

    U. Wissenbach; A. Kröger; G. Unden

    1990-01-01

    The respiratory activities of E. coli with H2 as donor and with nitrate, fumarate, dimethylsulfoxide (DMSO) or trimethylamine N-oxide (TMAO) as acceptor were measured using the membrane fraction of quinone deficient strains. The specific activities of the membrane fraction lacking naphthoquinones with fumarate, DMSO or TMAO amounted to ?2% of those measured with the membrane fraction of the wild-type strain.

  19. Electron transfer of quinone self-assembled monolayers on a gold electrode

    Microsoft Academic Search

    Morio Nagata; Masaharu Kondo; Yoshiharu Suemori; Tsuyoshi Ochiai; Takehisa Dewa; Toshiaki Ohtsuka; Mamoru Nango

    2008-01-01

    Dialkyl disulfide-linked naphthoquinone, (NQ-Cn-S)2, and anthraquinone, (AQ-Cn-S)2, derivatives with different spacer alkyl chains (Cn: n=2, 6, 12) were synthesized and these quinone derivatives were self-assembled on a gold electrode. The formation of self-assembled monolayers (SAMs) of these derivatives on a gold electrode was confirmed by infrared reflection-absorption spectroscopy (IR-RAS). Electron transfer between the derivatives and the gold electrode was studied

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

    Microsoft Academic Search

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

    2001-01-01

    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

  1. Naphthohydroquinone glucosides of Drosera rotundifolia and D. intermedia from in vitro cultures

    Microsoft Academic Search

    Jaromir Budzianowski

    1996-01-01

    Rossoliside (7-methylhydrojuglone 4-O-glucoside) was isolated from Drosera rotundifolia, together with hydroplumbagin 4-O-glucoside, from D. intermedia, both of which were produced by in vitro micropropagation. Hydroplumbagin glucoside released the corresponding 1,4-naphthoquinone (plumbagin) more rapidly than rossoliside (7-methyljuglone). These glucosides can be detected in plant extracts by reversed-phase TLC and appearance of the corresponding free quinones after treatment with ?-glucosidase.

  2. Pyrone polyketides synthesized by a type III polyketide synthase from Drosophyllum lusitanicum

    Microsoft Academic Search

    Aphacha Jindaprasert; Karin Springob; Jürgen Schmidt; Wanchai De-Eknamkul; Toni M. Kutchan

    2008-01-01

    To isolate cDNAs involved in the biosynthesis of acetate-derived naphthoquinones in Drosophyllum lusitanicum, an expressed sequence tag analysis was performed. RNA from callus cultures was used to create a cDNA library from which 2004 expressed sequence tags were generated. One cDNA with similarity to known type III polyketide synthases was isolated as full-length sequence and termed DluHKS. The translated polypeptide

  3. Epidemiological observations on theileriosis following field immunisation using infection and treatment

    Microsoft Academic Search

    J. J. Mutugi; A. S. Young; D. P. Kariuki; J. M. Ole Tameno; S. P. Morzaria

    1991-01-01

    Thirty-seven high grade cattle were immunised against Corridor disease (Theileria parva lawrencei infection) on a farm with a history of heavy and often lethal theilerial challenge. Nineteen cattle were immunised by treating with two doses of long-acting oxytetracyclines given at 20 mg\\/kg on days 0 and 4 after sporozoite stabilate inoculation, while the other 18 were treated with naphthoquinone buparvaquone,

  4. Relocalization of Cathepsin D and Cytochrome c Early in Apoptosis Revealed by Immunoelectron Microscopy

    Microsoft Academic Search

    Karin Roberg

    2001-01-01

    Cathepsin D was translocated from lysosomal structures to the cytosol in primary cultures of neonatal rat cardiomyocytes exposed to oxidative stress, and these cells underwent apoptotic death during subsequent incubation. Temporal aspects of cathepsin D relocalization, cytochrome c release, and decrease in mitochondrial transmembrane potential (??m) were studied in myocytes exposed to the redox-cycling xenobiotic naphthazarin (5,8-dihydroxy-1,4-naphthoquinone). Immunofluorescence labeling revealed

  5. Electrochemical analysis of natural solid organic dyes and pigments

    Microsoft Academic Search

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

    2003-01-01

    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

  6. Laboratory testing of the Hiperion liquid redox process. Final topical report, December 1991

    SciTech Connect

    Dalrymple, D.A.; Trofe, T.W.; DeBerry, D.W.

    1991-12-01

    Radian and Ultrasystems performed laboratory and bench-scale studies to obtain operational information on the Hiperion liquid redox sulfur recovery process. Specific activities included analytical methods development and verification, bench-scale testing, 1,4 naphthoquinone disulfonate stability testing, and reoxidation testing. A definite conclusion regarding the suitability of the Hiperion process for natural gas desulfurization could not be reached due to contractual difficulties which led to GRI's deferring the work.

  7. Laboratory testing of the Hiperion liquid redox process. Final topical report, December 1991

    Microsoft Academic Search

    D. A. Dalrymple; T. W. Trofe; D. W. DeBerry

    1991-01-01

    Radian and Ultrasystems performed laboratory and bench-scale studies to obtain operational information on the Hiperion liquid redox sulfur recovery process. Specific activities included analytical methods development and verification, bench-scale testing, 1,4 naphthoquinone disulfonate stability testing, and reoxidation testing. A definite conclusion regarding the suitability of the Hiperion process for natural gas desulfurization could not be reached due to contractual difficulties

  8. Photosynthetic bio-fuel cells using cyanobacteria

    Microsoft Academic Search

    T. Yagishita; S. Sawayama; K. Tsukahara; T. Ogi

    1996-01-01

    Effects of glycogen and glucose on the current outputs have been studied in photosynthetic bio-fuel cells using two kinds of cyanobacteria, Anabaena variabilis M-3 and Synechocystis sp. M-203, and 2-hydroxy-1,4-naphthoquinone. In the bio-fuel cell using Anabaena variabilis M-3, by repeating discharge-culture operation, the lifetime of the bio-fuel cell extended to net 80 hours, although the current output was sustained only

  9. Purification of sulfide oxidase from rat liver 

    E-print Network

    Pu, Lixia

    1994-01-01

    blue in 500 ml of water. The spectral curve of methylene blue was obtained with a uv-vis scanning spectrophotometer (Shimadzu, UV2101PC). A standard curve for methylene blue was obtained spectrally with known amounts of methylene blue measured at 600...), methylene blue methods (Selvapathy et a1. , 1989), uv-spectrophotometric determination based on the reaction with 2-iodo-I-methylpyridinium iodide (Bald and Ciesielski, 1988), spectrofluorometric determination with 1, 2-naphthoquinone-4-sulphonate (Punta...

  10. Discriminating Redox Cycling and Arylation Pathways of Reactive Chemical Toxicity in Trout Hepatocytes

    Microsoft Academic Search

    P. K. Schmieder; M. A. Tapper; R. C. Kolanczyk; D. E. Hammermeister; B. R. Sheedy; J. S. Denny

    2003-01-01

    The toxicity of four quinones, 2,3-dimethoxy-1,4-naphthoqui- none (DMONQ), 2-methyl-1,4-naphthoquinone (MNQ), 1,4-naph- thoquinone (NQ), and 1,4-benzoquinone (BQ), which redox cycle or arlyate in mammalian cells, was determined in isolated trout (Oncorhynchus mykiss) hepatocytes. More than 70% of cells died in 3 h when exposed to BQ or NQ; 50% died in 7 h when exposed to MNQ, with no mortality compared

  11. The Maillard Reaction for Sunlight Protection

    Microsoft Academic Search

    Ramon M. Fusaro; Edwin G. Rice

    2005-01-01

    During seven months of a clinical trial in spring, summer, and fall, 30 UVA\\/B\\/Soret band-photosensitive patients used sequential topical applications of dihydroxyacetone (DHA) followed by naphthoquinone only at bedtime and received excellent photoprotection without a single therapeutic failure or loss of any patient to follow-up. Eighteen of the 30 patients extended the limits of their photoprotection repeatedly over a seven-month

  12. ``Subversive'' Substrates for the Enzyme Trypanothione Disulfide Reductase: Alternative Approach to Chemotherapy of Chagas Disease

    Microsoft Academic Search

    Graeme B. Henderson; Peter Ulrich; Alan H. Fairlamb; Ian Rosenberg; Miercio Pereira; Michael Sela; Anthony Cerami

    1988-01-01

    The trypanosomatid flavoprotein disulfide reductase, trypanothione reductase, is shown to catalyze one-electron reduction of suitably substituted naphthoquinone and nitrofuran derivatives. A number of such compounds have been chemically synthesized, and a structure-activity relationship has been established; the enzyme is most active with compounds that contain basic functional groups in side-chain residues. The reduced products are readily reoxidized by molecular oxygen

  13. Two new compounds from Trigonostemon heterophyllus

    Microsoft Academic Search

    Yi-Xing Li; Wen-Li Mei; Wen-Jian Zuo; You-Xing Zhao; Wen-Hua Dong; Hao-Fu Dai

    Phytochemical investigation on the stems of Trigonostemon heterophyllus led to the isolation of a new diterpene, trigonoheterene (1), and a new naphthoquinone, trigonoheterone (2), together with two known compounds, 3,4-seco-sonderianol, (3) and trigonochinene E, (4). Their structures were determined by spectroscopic techniques (UV, IR, MS, 1D and 2D NMR). All compounds were evaluated for cytotoxic activities and antibacterial activities.

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

    PubMed Central

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

    2013-01-01

    ?-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. PMID:24023520

  15. Airborne quinones induce cytotoxicity and DNA damage in human lung epithelial A549 cells: the role of reactive oxygen species.

    PubMed

    Shang, Yu; Zhang, Ling; Jiang, Yuting; Li, Yi; Lu, Ping

    2014-04-01

    Ambient particulate matter (PM) is associated with adverse health effects. Quinones present in PM are hypothesized to contribute to these harmful effects through the generation of reactive oxygen species (ROS). However, whether the ROS induced by quinones is involved in mediating DNA damage as well as other biological responses in pulmonary cells is less well known. In this study, the toxic effects of five typical airborne quinones, including 1,2-naphthoquinone, 2-methylanthraquinone, 9,10-phenanthrenequinone, 2-methyl-1,4-naphthoquinone, and acenaphthenequinone, on cytotoxicity, DNA damage, intracellular calcium homeostasis, and ROS generation, were studied in human lung epithelial A549 cells. An antioxidant N-acetylcysteine (NAC) was used to examine the involvement of ROS in adverse biological responses induced by quinones. The quinones caused a concentration-dependent viability decrease, cellular LDH release, DNA damage, and ROS production in A549 cells. 1,2-Naphthoquinone, but not the other four quinones, increased intracellular calcium (Ca(2+)) levels in a dose-dependent manner. These toxic effects were abolished by administration of NAC, suggesting that ROS played a key role in the observed toxic effects of quinones in A549 cells. These results emphasize the importance of quinones in PM on the adverse health effects of PMs, which has been underestimated in the past few years, and highlight the need, when evaluating the effects on health and exposure management, to always consider their qualitative chemical compositions in addition to the size and concentration of PMs. PMID:24480427

  16. Computational Optimization of Bioanalytical Parameters for the Evaluation of the Toxicity of the Phytomarker 1,4 Napthoquinone and its Metabolite 1,2,4-trihydroxynapththalene

    PubMed Central

    Gopal, Velmani; AL Rashid, Mohammad Harun; Majumder, Sayani; Maiti, Partha Pratim; Mandal, Subhash C

    2015-01-01

    Objectives: Lawsone (1,4 naphthoquinone) is a non redox cycling compound that can be catalyzed by DT diaphorase (DTD) into 1,2,4-trihydroxynaphthalene (THN), which can generate reactive oxygen species by auto oxidation. The purpose of this study was to evaluate the toxicity of the phytomarker 1,4 naphthoquinone and its metabolite THN by using the molecular docking program AutoDock 4. Methods: The 3D structure of ligands such as hydrogen peroxide (H2O2), nitric oxide synthase (NOS), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) were drawn using hyperchem drawing tools and minimizing the energy of all pdb files with the help of hyperchem by MM+ followed by a semi-empirical (PM3) method. The docking process was studied with ligand molecules to identify suitable dockings at protein binding sites through annealing and genetic simulation algorithms. The program auto dock tools (ADT) was released as an extension suite to the python molecular viewer used to prepare proteins and ligands. Grids centered on active sites were obtained with spacings of 54 × 55 × 56, and a grid spacing of 0.503 was calculated. Comparisons of Global and Local Search Methods in Drug Docking were adopted to determine parameters; a maximum number of 250,000 energy evaluations, a maximum number of generations of 27,000, and mutation and crossover rates of 0.02 and 0.8 were used. The number of docking runs was set to 10. Results: Lawsone and THN can be considered to efficiently bind with NOS, CAT, GSH, GR, G6PDH and NADPH, which has been confirmed through hydrogen bond affinity with the respective amino acids. Conclusion: Naphthoquinone derivatives of lawsone, which can be metabolized into THN by a catalyst DTD, were examined. Lawsone and THN were found to be identically potent molecules for their affinities for selected proteins. PMID:26120483

  17. Sepiapterin reductase mediates chemical redox cycling in lung epithelial cells.

    PubMed

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

    2013-06-28

    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

  18. Sepiapterin Reductase Mediates Chemical Redox Cycling in Lung Epithelial Cells*

    PubMed Central

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

    2013-01-01

    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

  19. Role of oxidant stress in lawsone-induced hemolytic anemia.

    PubMed

    McMillan, David C; Sarvate, Snehal D; Oatis, John E; Jollow, David J

    2004-12-01

    Lawsone (2-hydroxy-1,4-naphthoquinone) is the active ingredient of henna (Lawsonia alba), the crushed leaves of which are used as a cosmetic dye. Application of henna can induce a severe hemolytic anemia, and lawsone is thought to be the causative agent. Administration of lawsone to rats has been shown to induce a hemolytic response that is associated with oxidative damage to erythrocytes. However, direct exposure of isolated erythrocytes to lawsone did not provoke oxidative damage, suggesting that lawsone must undergo extra-erythrocytic bioactivation in vivo. In the present study, the survival of rat 51Cr-labeled erythrocytes in vivo after in vitro exposure to lawsone and its hydroquinone form, 1,2,4-trihydroxynaphthalene (THN) has been examined. Neither lawsone nor THN were directly hemolytic or methemoglobinemic, even at high concentrations (>3 mM). Lawsone had no effect on erythrocytic GSH levels, whereas THN (3 mM) induced a modest depletion (approximately 30%). Cyclic voltammetry revealed that the lack of hemotoxicity of lawsone was associated with a poor capacity to undergo redox cycling. In contrast, ortho-substituted 1,4-naphthoquinones without a 2-hydroxy group, such as 2-methyl- and 2-methoxy-1,4-naphthoquinone, were redox active, were able to deplete GSH, and were direct-acting hemolytic agents. An oxidant stress-associated hemolytic response to lawsone could be provoked, however, if it was incubated with GSH-depleted erythrocytes. The data suggest that lawsone is a weak direct-acting hemolytic agent that does not require extra-erythrocytic metabolism to cause hemotoxicity. Thus, the hemolytic response to henna may be restricted to individuals with compromised antioxidant defenses. PMID:15456924

  20. Microwave-assisted rapid cyclization of lapachol, a main constituent of Heterophragma adenophyllum.

    PubMed

    Singh, P; Natani, K; Jain, S; Arya, K; Dandia, A

    2006-02-01

    Cyclization reactions of lapachol (1) isolated from Heterophragma adenophyllum have been studied under microwave irradiation under different conditions using alumina (acidic, basic and neutral)/silica gel/montmorillonite (KSF and K-10) as solid support along with neat reaction using 2-3 drops of DMF giving naturally occurring dehydro-alpha-lapachone (2), alpha-lapachone (3), beta-lapachone (4) depending upon the nature of support and irradiation time. A novel naphthoquinone derivative adenophyllone (5) can be synthesized from lapachol using DMF under microwaves. PMID:16496478

  1. Stimulation of oxyradical production of hepatic microsomes of flounder ( Platichthys flesus ) and perch ( Perca fluviatilis ) by model and pollutant xenobiotics

    Microsoft Academic Search

    P. Lemaire; A. Matthews; L. Förlin; D. R. Livingstone

    1994-01-01

    Stimulation of hepatic microsomal NAD(P)H-dependent hydroxyl radical (·OH) production by model compounds, viz. menadione (2-methyl-1,4-naphthoquinone) and nitrofurantoin (N-(5-nitro-2-furfurylidene)-1-aminohydantoin), and pollutant xenobiotics, viz. benzo[a]pyrene (BaP) diones (products of microsomal BaP metabolism), duroquinone (tetramethyl-1,4-benzoquinone—present in pulp mill effluent), and the pesticide lindane (?-hexachlorocyclohexane), was examined in flounder Platichthys flesus. Duroquinone was also studied in perch Perca fluviatilis, a freshwater species used in

  2. Organocatalyzed benzannulation for the construction of diverse anthraquinones and tetracenediones.

    PubMed

    Somai Magar, Krishna Bahadur; Xia, Likai; Lee, Yong Rok

    2015-05-01

    An efficient one-pot synthesis of anthraquinones and tetracenediones was achieved vial-proline catalyzed [4+2] cycloaddition of in situ generated azadiene from ?,?-unsaturated aldehydes and 1,4-naphthoquinones or 1,4-anthracenedione in good to excellent yield. This protocol constitutes an unprecedented tandem benzannulation that allows one-pot construction of diverse anthraquinones and tetracenediones in the presence of organocatalysts. This methodology was applied successfully to the synthesis of naturally occurring molecules and photochemically interesting phenanthrenequinone derivatives. PMID:25858160

  3. Formation of nanotunnels inside a resist film in laser interference lithography.

    PubMed

    Wei, Qi; Hu, Fanhua; Wang, Liyuan

    2015-05-19

    A few kinds of 2-diazo-1-naphthoquinone-4-sulfonates of poly(4-hydroxylstyrene) were prepared to form one-component i-line photoresists. In the laser interference lithography experiments of some of the photoresists, nanotunnels were observed to be aligned in the interior of the resist film. The shape and size of the nanotunnels remain virtually unchanged even under an increased exposure dose, indicating that the exposure energy is confined within the tunnel space. The formation of the nanotunnels results from the effect of standing waves and the permeation of developer from the surface deep into the resist films. PMID:25938301

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

    Microsoft Academic Search

    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

    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

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

    PubMed

    Hausen, B M; Schiedermair, I

    1988-09-01

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

  6. A new dilactone from the seeds of Gaultheria yunnanensis

    Microsoft Academic Search

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

    2010-01-01

    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-?-d-xylosyl(1?6)?-d-glucopyranoside (7), and methyl salicylate 2-O-?-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

  7. 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

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

    2008-01-01

    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

  8. Hydroxynaphthoquinone Metal Complexes as Antitumor Agents X: Synthesis, Structure, Spectroscopy and In Vitro Antitumor Activity of 3-Methyl-Phenylazo Lawsone Derivatives and Their Metal Complexes Against Human Breast Cancer Cell Line MCF-7

    PubMed Central

    Gokhale, Nikhil; Newton, Chris; Pritchard, Robin

    2000-01-01

    The C-3 substituted phenylazo derivatives of lawsone (2-hydroxy-l,4 p-naphthoquinone, III) were synthesized and characterized. The X-ray crystal structure was determined for the ligand 3-(3?-methyl phenylazo) lawsone. The copper complexes of these derivatives were found to possess 1:2 metal stoichiometry and square planar geometries with intermolecular stackings, resulting in antiferromagnetic exchange interactions. The in vitro activity of all the synthesized compounds was examined against human breast cancer cell-line, MCF-7, which revealed enhanced activities for the metal complexes, the highest activity being observed for the copper compound of 3-(3?-methyl phenylazo) lawsone. PMID:18475934

  9. Hydroxynaphthoquinone metal complexes as antitumor agents x: synthesis, structure, spectroscopy and in vitro antitumor activity of 3-methyl-phenylazo lawsone derivatives and their metal complexes against human breast cancer cell line mcf-7.

    PubMed

    Gokhale, N; Padhye, S; Newton, C; Pritchard, R

    2000-01-01

    The C-3 substituted phenylazo derivatives of lawsone (2-hydroxy-l,4 p-naphthoquinone, III) were synthesized and characterized. The X-ray crystal structure was determined for the ligand 3-(3'-methyl phenylazo) lawsone. The copper complexes of these derivatives were found to possess 1:2 metal stoichiometry and square planar geometries with intermolecular stackings, resulting in antiferromagnetic exchange interactions. The in vitro activity of all the synthesized compounds was examined against human breast cancer cell-line, MCF-7, which revealed enhanced activities for the metal complexes, the highest activity being observed for the copper compound of 3-(3'-methyl phenylazo) lawsone. PMID:18475934

  10. Reaction of 1,2,3,4-tetrahydro-isoquinoline enamines with quinones

    Microsoft Academic Search

    N. N. Polygalova; A. G. Mikhailovskii; M. I. Vakhrin

    2006-01-01

    The reaction of p-benzoquinone with enamino amides derived from 2,2-dimethyl-1,2,3,4-tetrahydrobenzo[f]isoquinoline proceeds\\u000a through a Michael addition. The reaction of this quinone with the base of drotaverine leads to a derivative of indolo[2,1-a]isoquinoline.\\u000a Fusion of isoquinoline enamines by the action of 2,3-dichloro-1,4-naphthoquinone leads to pentacyclic benzo[g]naphtho-[2,3-b]indolyzine-8,13-dione.

  11. Annelation of drotaverine by p -quinones to form hydroxyindolo- and hydroxybenzindoloisoquinoline derivatives

    Microsoft Academic Search

    L. Yu. Ukhin; T. N. Gribanova; L. G. Kuz’mina

    2005-01-01

    1-(3, 4-Diethoxybenzyl)-6, 7-diethoxy-3, 4-dihydroisoquinoline (drotaverine, 1a) reacts with p-benzoquinone (2) and p-naphthoquinone (3) in nitromethane or during fusion to give 5-(3, 4-diethoxyphenyl)-7, 8-diethoxy-3-hydroxy-5a, 10, 11, 12-tetrahydroindolo[2, 1-a]isoquinoline (4) and 7-(3, 4-diethoxyphenyl)-9, 10-diethoxy-5-hydroxy-7a, 12, 13, 14-tetrahydrobenz[g]indolo[2, 1-a]isoquinoline (5), respectively. Compounds 4 and 5 are smoothly alkylated at the oxygen atom in the presence of bases. The structure of one alkylation product,

  12. Anticancer Compound Plumbagin and Its Molecular Targets: A Structural Insight into the Inhibitory Mechanisms Using Computational Approaches

    PubMed Central

    Beg, Mohd A.; Suhail, Mohd; Chaudhary, Adeel G. A.; Damanhouri, Ghazi A.; Abuzenadah, Adel M.; Rehan, Mohd

    2014-01-01

    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

  13. 5-O-Acyl plumbagins inhibit DNA polymerase activity and suppress the inflammatory response.

    PubMed

    Onodera, Takefumi; Kuriyama, Isoko; Sakamoto, Yuka; Kawamura, Moe; Kuramochi, Kouji; Tsubaki, Kazunori; Tabata, Atsushi; Naganune, Hideaki; Mizushina, Yoshiyuki

    2015-05-01

    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 displayed enhanced mammalian pol inhibition, with plumbagin conjugated to docosahexaenoic acid (C22:6-acyl plumbagin) exhibiting the strongest inhibition of pol ? among the ten 5-O-acyl plumbagins synthesized. C22:6-acyl plumbagin selectively inhibited the activities of mammalian pol species, but did not influence the activities of other pols or DNA metabolic enzymes tested. The inhibition of pol ?, a DNA repair/recombination pol, by these compounds was significantly correlated with both their suppression of lipopolysaccharide (LPS) induced tumor necrosis factor-? (TNF-?) production by mouse RAW264.7 macrophages and the reduction of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in the mouse ear. These data indicate that 5-O-acyl plumbagins act as anti-inflammatory agents by inhibiting mammalian pol ?. These results further suggest that C22:6-acyl plumbagin is a promising anti-inflammatory candidate and that acylation could be an effective chemical modification to improve the anti-inflammatory activity of vitamin K3 derivatives, such as plumbagin. PMID:25748000

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

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

  16. Chemiluminescence assay for quinones based on generation of reactive oxygen species through the redox cycle of quinone.

    PubMed

    Kishikawa, Naoya; Ohkubo, Nobuhiro; Ohyama, Kaname; Nakashima, Kenichiro; Kuroda, Naotaka

    2009-02-01

    A sensitive and selective chemiluminescence assay for the determination of quinones was developed. The method was based on generation of reactive oxygen species through the redox reaction between quinone and dithiothreitol as reductant, and then the generated reactive oxygen was detected by luminol chemiluminescence. The chemiluminescence was intense, long-lived, and proportional to quinone concentration. It is concluded that superoxide anion was involved in the proposed chemiluminescence reaction because the chemiluminescence intensity was decreased only in the presence of superoxide dismutase. Among the tested quinones, the chemiluminescence was observed from 9,10-phenanthrenequinone, 1,2-naphthoquinone, and 1,4-naphthoquinone, whereas it was not observed from 9,10-anthraquinone and 1,4-benzoquinone. The chemiluminescence property was greatly different according to the structure of quinones. The chemiluminescence was also observed for biologically important quinones such as ubiquinone. Therefore, a simple and rapid assay for ubiquinone in pharmaceutical preparation was developed based on the proposed chemiluminescence reaction. The detection limit (blank + 3SD) of ubiquinone was 0.05 microM (9 ng/assay) with an analysis time of 30 s per sample. The developed assay allowed the direct determination of ubiquinone in pharmaceutical preparation without any purification procedure. PMID:19066858

  17. Microbial electricity generation of diversified carbonaceous electrodes under variable mediators.

    PubMed

    Park, In Ho; In Ho, Park; Gnana Kumar, G; Kim, A R; Kim, Pil; Suk Nahm, Kee

    2011-02-01

    To evaluate a suitable electrode material for the efficient green energy generation of a bio-fuel cell, carbonaceous based carbon cloth, carbon paper, and carbon felt electrodes were investigated under different mediators. The larger surface area, low resistance, and open network of interwoven fibers of the carbon felt electrode facilitated higher electron transfer from the microbial organisms to the electrode surface than that of other carbonaceous electrodes. Carbon paper electrode exhibited lower fuel cell performances due to its lower roughness and high tortuous nature. The green power generation experiments were also carried out under different mediators such as 2-hydroxy-l,4-naphthoquinone and thionin. The electrons mitigation and power generation was augmented by 2-hydroxy-l,4-naphthoquinone than thionin due to its high solubility, stability, and minimal adsorption characteristic to the electrodes. By the combined efforts of extended electrons generation and transportation, bio-fuel cell performances were extended and endorsed its doable applications in bio-fuel cells. PMID:20655812

  18. Pyrone polyketides synthesized by a type III polyketide synthase from Drosophyllum lusitanicum.

    PubMed

    Jindaprasert, Aphacha; Springob, Karin; Schmidt, Jürgen; De-Eknamkul, Wanchai; Kutchan, Toni M

    2008-12-01

    To isolate cDNAs involved in the biosynthesis of acetate-derived naphthoquinones in Drosophyllum lusitanicum, an expressed sequence tag analysis was performed. RNA from callus cultures was used to create a cDNA library from which 2004 expressed sequence tags were generated. One cDNA with similarity to known type III polyketide synthases was isolated as full-length sequence and termed DluHKS. The translated polypeptide sequence of DluHKS showed 51-67% identity with other plant type III PKSs. Recombinant DluHKS expressed in Escherichia coli accepted acetyl-coenzyme A (CoA) as starter and carried out sequential decarboxylative condensations with malonyl-CoA yielding alpha-pyrones from three to six acetate units. However, naphthalenes, the expected products, were not isolated. Since the main compound produced by DluHKS is a hexaketide alpha-pyrone, and the naphthoquinones in D. lusitanicum are composed of six acetate units, we propose that the enzyme provides the backbone of these secondary metabolites. An involvement of accessory proteins in this biosynthetic pathway is discussed. PMID:18466932

  19. Naphthazarin enhances ionizing radiation-induced cell cycle arrest and apoptosis in human breast cancer cells.

    PubMed

    Kim, Min Young; Park, Seong-Joon; Shim, Jae Woong; Yang, Kwangmo; Kang, Ho Sung; Heo, Kyu

    2015-04-01

    Naphthazarin (Naph, DHNQ, 5,8-dihydroxy-l,4-naphthoquinone) is one of the naturally available 1,4-naphthoquinone derivatives that are well-known for their anti-inflammatory, antioxidant, antibacterial and antitumor cytotoxic effects in cancer cells. Herein, we investigated whether Naph has effects on cell cycle arrest and apoptosis in MCF-7 human breast cancer cells exposed to ionizing radiation (IR). Naph reduced the MCF-7 cell viability in a dose-dependent manner. We also found that Naph and/or IR increased the p53-dependent p21 (CIP/WAF1) promoter activity. Noteworthy, our ChIP assay results showed that Naph and IR combined treatment activated the p21 promoter via inhibition of binding of multi-domain proteins, DNMT1, UHRF1 and HDAC1. Apoptosis and cell cycle analyses demonstrated that Naph and IR combined treatment induced cell cycle arrest and apoptosis in MCF-7 cells. Herein, we showed that Naph treatment enhances IR-induced cell cycle arrest and death in MCF-7 human breast cancer cells through the p53-dependent p21 activation mechanism. These results suggest that Naph might sensitize breast cancer cells to radiotherapy by enhancing the p53-p21 mechanism activity. PMID:25633658

  20. Combination of chiroptical, absorption and fluorescence spectroscopic methods reveals multiple, hydrophobicity-driven human serum albumin binding of the antimalarial atovaquone and related hydroxynaphthoquinone compounds.

    PubMed

    Zsila, Ferenc; Fitos, Ilona

    2010-11-01

    High-affinity human serum albumin (HSA) binding of the C3-substituted antimalarial 2-hydroxy-1,4-naphthoquinone derivative atovaquone (ATQ) has been demonstrated and studied by circular dichroism (CD), UV/VIS absorption, fluorescence spectroscopy and affinity chromatography methods. The analysis of induced CD data generated upon HSA binding of ATQ revealed two high-affinity binding sites (K(a) ? 2 × 10(6) M(-1)). CD interaction studies and displacement of specific fluorescent and radioactive marker ligands indicated the contribution of both principal drug binding sites of HSA to complexation of ATQ, and also suggested the possibility of simultaneous binding of ATQ and some other drugs (e.g. warfarin, phenylbutazone, diazepam). Comparison of UV/VIS spectra of ATQ measured in aqueous solutions indicated the prevalence of the anionic species formed by dissociation of the 2-hydroxyl group. HSA binding of related natural hydroxynaphthoquinones, lapachol and lawsone also induces similar CD spectra. The much weaker binding affinity of lawsone (K(a) ? 10(4) M(-1)) bearing no C3 substituent highlights the importance of hydrophobic interactions in the strong HSA binding of ATQ and lapachol. Since neither drug exhibited significant binding to serum ?(1)-acid glycoprotein, HSA must be the principal plasma protein for the binding and transportation of 2-hydroxy-1,4-naphthoquinone-type compounds which are ionized at physiological pH values. PMID:20737064

  1. Mutagenic activity of isoxazolylnaphthoquinoneimines assayed by micronucleus bone marrow test.

    PubMed

    Sicardi, S M; Ferrato, E

    1995-05-01

    Studies were undertaken to evaluate the ability of various quinoneimines to induce micronuclei in bone marrow cells as a measure of their genotoxicity. Accordingly, 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (I), its 2-acetyl derivative (II) and 2-[(5-methyl-3-isoxazolyl)amino]-N-(5-methyl-3-isoxazolyl)-1 ,4- naphthoquinone-4-imine (III), as well as two of their precursors, 2-hydroxynaphthoquinone (NQ-2-OH) and 3,4-dimethyl-5-aminoisoxazole (DMAI) were given by intraperitoneal injection at 5, 50, 100 and 200 mg/Kg doses to S.J.L. Swiss mice with 24 h sampling time. Compounds I and II displayed highly significant differences at 50, 100 and 200 mg/kg doses (p < 0.01) and their mutagenic dose response curves correlated closely with an inverted U-shaped form whose interpretation is still the subject of controversy. NQ-2-OH only produced a significant increase in micronucleus frequency at 50 mg/kg, whereas no mutagenic activity was found for compound III and DMAI at the doses assayed. At 50 mg/kg the order of relative mutagenic potencies was I > II > NQ-2-OH. Mechanisms advanced to explain loss of drug activity at high doses include capture saturation, enzymatic induction during metabolism and participation of an independent defense system. PMID:7753107

  2. Identification of Quinoide Redox Mediators That Are Formed during the Degradation of Naphthalene-2-Sulfonate by Sphingomonas xenophaga BN6

    PubMed Central

    Keck, Andreas; Rau, Jörg; Reemtsma, Thorsten; Mattes, Ralf; Stolz, Andreas; Klein, Joachim

    2002-01-01

    During aerobic degradation of naphthalene-2-sulfonate (2NS), Sphingomonas xenophaga strain BN6 produces redox mediators which significantly increase the ability of the strain to reduce azo dyes under anaerobic conditions. It was previously suggested that 1,2-dihydroxynaphthalene (1,2-DHN), which is an intermediate in the degradative pathway of 2NS, is the precursor of these redox mediators. In order to analyze the importance of the formation of 1,2-DHN, the dihydroxynaphthalene dioxygenase gene (nsaC) was disrupted by gene replacement. The resulting strain, strain AKE1, did not degrade 2NS to salicylate. After aerobic preincubation with 2NS, strain AKE1 exhibited much higher reduction capacities for azo dyes under anaerobic conditions than the wild-type strain exhibited. Several compounds were present in the culture supernatants which enhanced the ability of S. xenophaga BN6 to reduce azo dyes under anaerobic conditions. Two major redox mediators were purified from the culture supernatants, and they were identified by high-performance liquid chromatography-mass spectrometry and comparison with chemically synthesized standards as 4-amino-1,2-naphthoquinone and 4-ethanolamino-1,2-naphthoquinone. PMID:12200285

  3. The maillard reaction for sunlight protection.

    PubMed

    Fusaro, Ramon M; Rice, Edwin G

    2005-06-01

    During seven months of a clinical trial in spring, summer, and fall, 30 UVA/B/Soret band-photosensitive patients used sequential topical applications of dihydroxyacetone (DHA) followed by naphthoquinone only at bedtime and received excellent photoprotection without a single therapeutic failure or loss of any patient to follow-up. Eighteen of the 30 patients extended the limits of their photoprotection repeatedly over a seven-month period to tolerate without sunburns six to eight hours of midday sunlight under all kinds of occupational and recreational environmental conditions. Previously, the use of 3% DHA topically in earlier studies gave only a sun protection factor (SPF) of 3. In this reanalysis of the original notes of a previous clinical study of the melanoidins produced by DHA followed by naphthoquinone in the keratin layers of the epidermis of minimally pigmented Caucasian photosensitive patients, it is determined that these patients received a minimal UVB photoprotection of SPF 18 or more. This represents at least a sixfold amplification of the UVB photoprotective effect over the use of only dihydroxyacetone in the Maillard reaction. PMID:16037237

  4. Synthesis and optical properties of acidochromic amine-substituted benzo[a]phenazines.

    PubMed

    Singh, Prachi; Baheti, Abhishek; Thomas, K R Justin

    2011-08-01

    A new series of alkylamine- or arylamine-substituted benzo[a]phenazines have been synthesized from 1,2-naphthoquinones by employing simple sequential Michael-type addition with a variety of primary and secondary amines and the condensation reaction of the resulting amine-substituted 1,2-naphthoquinones with o-phenylenediamine. They exhibited absorption peaks originating from the charge transfer transition between the amine and pyrazine segments and benzo[a]phenazine localized ?-?* transitions. Although the absorption spectra of the dyes were not significantly influenced by the nature of the solvents, addition of TFA led to a prominent red-shift in the absorption spectra owing to the protonation at the quinoxaline segment which enhanced the electron-accepting ability. The qualitative trends observed in the optical properties and acidochromism were supported by density functional theoretical computations. The dyes displayed positive solvatochromism in the emission spectra suggestive of a more polar excited state. The dyes were also characterized by a quasi-reversible reduction couple originating from the pyrazine segment which underwent shifts corresponding to electron-donating strength of the amine segment. PMID:21644579

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

    PubMed Central

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

    2014-01-01

    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

  6. Inhibition of the mutagenicity of 2-nitrofluorene, 3-nitrofluoranthene and 1-nitropyrene by flavonoids, coumarins, quinones and other phenolic compounds.

    PubMed

    Edenharder, R; Tang, X

    1997-01-01

    When 56 flavonoids, 32 coumarins, five naphthoquinones, 12 anthraquinones and five structurally-related compounds were tested for their antimutagenic potencies with respect to mutagenicities induced by 2-nitrofluorene (2-NF), 3-nitrofluoranthene (3-NFA) and 1-nitropyrene (1-NP) in Salmonella typhimurium TA98 distinct structure-activity relationships were detected. First, the tetracyclic nitroarenes 3-NFA and 1-NP were in general more effectively antagonized by potent antimutagenic flavonoids and coumarins than the tricyclic 2-NF, while there were only minor differences with quinones. Secondly, antimutagenicity of natural compounds of plant origin correlated with the aglyconic nature 10 of a total of 15 glycosides were inactive, four flavonoid glycosides exerted antimutagenicity but to a distinctly lower degree than the corresponding aglycones. Thirdly, within flavonoids, coumarins and anthraquinones positive correlations were found between antimutagenic potency and the polarity of a molecule with the existence of an optimum of activity within flavonols and anthraquinones. However, polarity seemed to be unimportant within the chalcone and naphthoquinone series. Among flavonoids, the parent compounds flavone and flavanone were inactive, but all flavones and many flavonoids with phenolic hydroxyl groups exerted antimutagenicity. Antimutagenic potency reached a maximum with the presence of four hydroxyl functions-luteolin, kaempferol-though the position of hydroxyls was also a determinant of antimutagenic potency. Methylation of phenolic hydroxyl groups, however, always reduced antimutagenicity. A carbonyl group at carbon 4 was essential for antimutagenicity: two catechins and anthocyanidins each were inactive. On the other hand, ring C of the flavane nucleus was not essential for antimutagenicity: chalcones and dihydrochalcones were potent antimutagens. Among coumarins, the parent compound showed antimutagenicity against 1-NP and 3-NFA, although dihydrocoumarin, methylcoumarins and compounds with bulky substituents were inactive. Otherwise, antimutagenic activity depended on the presence of polar hydroxyl, amino or carboxyl groups at carbons 3, 4 or 7 but was diminished by interactions of hydroxyl groups vicinal to carbon 7. Again, antimutagenic potencies were reduced by alkylation or acetylation. Among furanocoumarins xanthotoxin exerted strong and bergapten moderate antimutagenicity, while psoralen (except against 3-NFA), isopimpinellin and the furanochromanones visnagin and khellin were inactive. Among anthraquinones, the principles delineated here were valid again, resulting in potent antimutagenicity of most phenolic compounds and inactivity of anthraquinone itself. Among compounds structurally related to anthraquinones, anthrone, acridone and xanthone exerted antimutagenicity, anthrone being the most potent one, while thioxanthone and 9-fluorenone were inactive. All naphthoquinones were potent antimutagens irrespective of the presence of methyl or hydroxyl functions. Plumbagin, 2-methyl-5-hydroxynaphthoquinone, however, showed exceptional antimutagenicity. PMID:9207898

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

    PubMed

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

    2001-10-01

    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

  8. Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid.

    PubMed

    Knecht, W; Henseling, J; Löffler, M

    2000-01-01

    Mitochondrially-bound dihydroorotate dehydrogenase (EC 1.3.99.11) catalyzes the fourth sequential step in the de novo synthesis of uridine monophosphate. The enzyme has been identified as or surmised to be the pharmacological target for isoxazol, triazine, cinchoninic acid and (naphtho)quinone derivatives, which exerted antiproliferative, immunosuppressive, and antiparasitic effects. Despite this broad spectrum of biological and clinical relevance, there have been no comparative studies on drug-dihydroorotate dehydrogenase interactions. Here, we describe a study of the inhibition of the purified recombinant human and rat dihydroorotate dehydrogenase by ten compounds. 1,4-Naphthoquinone, 5,8-hydroxy-naphthoquinone and the natural compounds juglon, plumbagin and polyporic acid (quinone derivative) were found to function as alternative electron acceptors with 10-30% of control enzyme activity. The human and rat enzyme activity was decreased by 50% by the natural compound lawsone ( > 500 and 49 microM, respectively) and by the derivatives dichloroally-lawsone (67 and 10 nM), lapachol (618 and 61 nM) and atovaquone (15 microM and 698 nM). With respect to the quinone co-substrate of the dihydroorotate dehydrogenase, atovaquone (Kic = 2.7 microM) and dichloroally-lawsone (Kic = 9.8 nM) were shown to be competitive inhibitors of human dihydroorotate dehydrogenase. Atovaquone (Kic = 60 nM) was also acompetitive inhibitor of the rat enzyme. Dichloroally]-lawsone was found to be a time-dependent inhibitor of the rat enzyme, with the lowest inhibition constant (Ki* = 0.77 nM) determined so far for mammalian dihydroorotate dehydrogenases. Another inhibitor, brequinar was previously reported to be a slow-binding inhibitor of the human dihydroorotate dehydrogenase [W. Knecht, M. Loffler, Species-related inhibition of human and rat dihyroorotate dehydrogenase by immunosuppressive isoxazol and cinchoninic acid derivatives, Biochem. Pharmacol. 56 (1998) 1259-1264]. The slow binding features of this potent inhibitor (Ki* = 1.8 nM) with the human enzyme, were verified and seen to be one of the reasons for the narrow therapeutic window (efficacy versus toxicity) reported from clinical trials on its antiproliferative and immunosuppressive action. With respect to the substrate dihydroorotate, atovaquone was an uncompetitive inhibitor of human dihydroorotate dehydrogenase (Kiu = 11.6 microM) and a non-competitive inhibitor of the rat enzyme (Kiu = 905/ Kic = 1,012 nM). 1.5 mM polyporic acid, a natural quinone from fungi, influenced the activity of the human enzyme only slightly; the activity of the rat enzyme was decreased by 30%. PMID:10658902

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

    PubMed

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

    2014-08-01

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

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

    PubMed

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

    2005-04-01

    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

  11. In vitro antispasmodic and anti-inflammatory effects of Drosera rotundifolia.

    PubMed

    Krenn, Liselotte; Beyer, Gabriele; Pertz, Heinz H; Karall, Elisabeth; Kremser, Michaela; Galambosi, Bertalan; Melzig, Matthias F

    2004-01-01

    In investigations of the anti-inflammatory and spasmolytic effects of Drosera rotundifolia two extracts were tested in different in vitro assays. An aqueous and an ethanolic extract inhibited human neutrophil elastase, achieving IC50 values of 5 and 1 microg/mL, respectively. The very low naphthoquinone concentrations in the extracts seem not to be responsible for the effect, as the pure compounds were not effective in the test system used. Thus, flavonoids like hyperoside, quercetin and isoquercitrin, which were detected in the extracts in considerable concentrations, may contribute to the activity. These substances showed activity in the assay. Ellagic acid, detected especially in the ethanolic extract in higher amounts, was substantially less active than the flavonoids. In guinea-pig ileum the extracts led to an antispasmodic effect possibly by affecting an allosteric binding site of the muscarinic M3 receptors. PMID:15344845

  12. Inhibition of the HIF1?-p300 interaction by quinone- and indandione-mediated ejection of structural Zn(II).

    PubMed

    Jayatunga, Madura K P; Thompson, Sam; McKee, Tawnya C; Chan, Mun Chiang; Reece, Kelie M; Hardy, Adam P; Sekirnik, Rok; Seden, Peter T; Cook, Kristina M; McMahon, James B; Figg, William D; Schofield, Christopher J; Hamilton, Andrew D

    2015-04-13

    Protein-protein interactions between the hypoxia inducible factor (HIF) and the transcriptional coactivators p300/CBP are potential cancer targets due to their role in the hypoxic response. A natural product based screen led to the identification of indandione and benzoquinone derivatives that reduce the tight interaction between a HIF-1? fragment and the CH1 domain of p300. The indandione derivatives were shown to fragment to give ninhydrin, which was identified as the active species. Both the naphthoquinones and ninhydrin were observed to induce Zn(II) ejection from p300 and the catalytic domain of the histone demethylase KDM4A. Together with previous reports on the effects of related compounds on HIF-1? and other systems, the results suggest that care should be taken in interpreting biological results obtained with highly electrophilic/thiol modifying compounds. PMID:25023609

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

    PubMed

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

    2013-12-01

    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

  14. Synthesis, Photochemical Properties, and Cytotoxicities of 2H-Naphtho[1,2-b]pyran and Its Photodimers.

    PubMed

    Ota, Motohiro; Sasamori, Takahiro; Tokitoh, Norihiro; Onodera, Takefumi; Mizushina, Yoshiyuki; Kuramochi, Kouji; Tsubaki, Kazunori

    2015-06-01

    A 2H-naphtho[1,2-b]pyran, prepared by dimerization of 2-bromo-3-methyl-1,4-naphthoquinone and O-methylation, readily undergoes solid-state [2 + 2] photodimerization to give a photodimer in excellent yield and with excellent selectivity. Retro [2 + 2] cycloaddition can be achieved by irradiation of a solution of the photodimer in chloroform. Interestingly, the 2H-naphtho[1,2-b]pyran dimerizes with a skeletal rearrangement to afford 2,5-dihydro-1-benzoxepin dimers upon irradiation in methanol or via irradiation with hexamethylditin. Furthermore, treatment of the resulting dimers with triethylamine regenerates the 2H-naphtho[1,2-b]pyran monomer. Significant differences in the color, fluorescence, and cytotoxic properties of the monomer and dimers were observed. PMID:25927340

  15. A new dilactone from the seeds of Gaultheria yunnanensis.

    PubMed

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

    2010-01-01

    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

  16. Quinone reduction by Rhodothermus marinus succinate:menaquinone oxidoreductase is not stimulated by the membrane potential

    SciTech Connect

    Fernandes, Andreia S. [Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Av. da Republica, Apartado 127, 2784-505 Oeiras (Portugal); Konstantinov, Alexander A. [Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Av. da Republica, Apartado 127, 2784-505 Oeiras (Portugal); A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow (Russian Federation); Teixeira, Miguel [Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Av. da Republica, Apartado 127, 2784-505 Oeiras (Portugal); Pereira, Manuela M. [Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Av. da Republica, Apartado 127, 2784-505 Oeiras (Portugal)]. E-mail: mpereira@itqb.unl.pt

    2005-05-06

    Succinate:quinone oxidoreductase (SQR), a di-haem enzyme purified from Rhodothermus marinus, reveals an HQNO-sensitive succinate:quinone oxidoreductase activity with several menaquinone analogues as electron acceptors that decreases with lowering the redox midpoint potential of the quinones. A turnover with the low-potential 2,3-dimethyl-1,4-naphthoquinone that is the closest analogue of menaquinone, although low, can be detected in liposome-reconstituted SQR. Reduction of the quinone is not stimulated by an imposed K{sup +}-diffusion membrane potential of a physiological sign (positive inside the vesicles). Nor does the imposed membrane potential increase the reduction level of the haems in R. marinus SQR poised with the succinate/fumarate redox couple. The data do not support a widely discussed hypothesis on the electrogenic transmembrane electron transfer from succinate to menaquinone catalysed by di-haem SQRs. The role of the membrane potential in regulation of the SQR activity is discussed.

  17. Lawsone dimerization in cobalt(III) complexes toward the design of new prototypes of bioreductive prodrugs.

    PubMed

    Bustamante, Francisco L S; Metello, Julia M; de Castro, Frederico A V; Pinheiro, Carlos B; Pereira, Marcos D; Lanznaster, Mauricio

    2013-02-01

    Dimerization of lawsone occurs upon reaction with Co(BF(4))(2)·6H(2)O and N,N'-bis(pyridin-2-ylmethyl)ethylenediamine (py(2)en) to produce the mononuclear complex [Co(III)(bhnq)(py(2)en)]BF(4)·H(2)O (1). This complex has been investigated as a prototype of a bioreductive prodrug, where the bhnq(2-) ligand acts as a model for cytotoxic naphthoquinones. Cyclic voltammetry data in aqueous solution have shown a quasi-reversible Co(III)/Co(II) process at E(1/2) = -0.26 V vs Fc/Fc(+). Reactivity studies revealed the dissociation of bhnq(2-) from the complex upon reduction of 1 with ascorbic acid, and a dependence of the reaction rate on the oxygen concentration suggests the occurrence of redox cycling. PMID:23343393

  18. Complexation equilibria and spectrophotometric determination of thorium(IV) with Lawsone.

    PubMed

    al-Nady, A B; al-Shaibi, Y; Ba-Issa, A; Ariqui, W

    2001-01-01

    The complex equilibria of Th4+ with Lawsone (2-hydroxy-1,4-naphthoquinone, LAS) were studied spectrophotometrically in 40% (v/v) ethanol water at 25 degrees C and an ionic strength of 0.1 M (NaClO4). The absorbance graphs were analysed to demonstrate and characterize the complex forming equilibria. A simple, rapid, selective and sensitive method for the spectrophotometric determination of trace amounts of thorium(IV) is developed. The complex formed at pH 2.1-3.6 (epsilon = 0.27 x 10(4) cm2 mol-1, at lambda = 440 nm) allows the determination of 5.8-32 micrograms/ml thorium. The effect of interferences was studied. PMID:11770165

  19. Novel zinc(II) and copper(II) complexes of a Mannich base derived from lawsone: Synthesis, single crystal X-ray analysis, ab initio density functional theory calculations and vibrational analysis.

    PubMed

    Neves, Amanda P; Vargas, Maria D; Téllez Soto, Claudio A; Ramos, Joanna M; Visentin, Lorenzo do C; Pinheiro, Carlos B; Mangrich, Antônio S; de Rezende, Edivaltrys I P

    2012-08-01

    Zinc(II) and copper(II) complexes of a tridentate Mannich base L1 derived from 2-hydroxy-1,4-naphthoquinone, pyridinecarboxyaldehyde and 2-aminomethylpyridine, [ZnL1Cl(2)]·H(2)O 1 and [CuL1Cl(2)]·2H(2)O 2, have been synthesized and fully characterized. The structure of complex 1 has been elucidated by a single crystal X-ray diffraction study: the zinc atom is pentacoordinate and the coordination geometry is a distorted square base pyramid, with a geometric structural parameter ? equal to 0.149. Vibrational spectroscopy and ab initio DFT calculations of both compounds have confirmed that the two complexes exhibit similar structures. Full assignment of the vibrational spectra was also supported by careful analysis of the distorted geometries generated by the normal modes. PMID:22513170

  20. Design and synthesis of a novel series of pyranonaphthoquinones as topoisomerase II catalytic inhibitors.

    PubMed

    Jiménez-Alonso, Sandra; Orellana, Haydee Chávez; Estévez-Braun, Ana; Ravelo, Angel G; Pérez-Sacau, Elisa; Machín, Felix

    2008-11-13

    On the basis of previous pharmacophore modeling studies of naphthoquinones derivatives, we have designed and synthesized a new set of pyranonaphthoquinones. These compounds were obtained through a direct and highly efficient approach based on an intramolecular domino Knoevenagel hetero Diels-Alder reaction from lawsone (2-hydroxynaphthoquinone) and a variety of aldehydes containing an alkene. The synthesized pyranonaphthoquinones were evaluated against the alpha isoform of human topoisomerase II (hTopoIIalpha). Among the 11 derivatives studied, we found that six of them act as catalytic inhibitors of the enzyme in vitro. These six derivatives strongly preclude the enzyme from decatenating or relaxing suitable substrates. Finally, we correlate their active/inactive status with docking studies of these novel compounds into the ATPase domain of hTopoIIalpha. PMID:18816045

  1. Novel zinc(II) and copper(II) complexes of a Mannich base derived from lawsone: Synthesis, single crystal X-ray analysis, ab initio density functional theory calculations and vibrational analysis

    NASA Astrophysics Data System (ADS)

    Neves, Amanda P.; Vargas, Maria D.; Soto, Claudio A. Téllez; Ramos, Joanna M.; Visentin, Lorenzo do C.; Pinheiro, Carlos B.; Mangrich, Antônio S.; de Rezende, Edivaltrys I. P.

    Zinc(II) and copper(II) complexes of a tridentate Mannich base L1 derived from 2-hydroxy-1,4-naphthoquinone, pyridinecarboxyaldehyde and 2-aminomethylpyridine, [ZnL1Cl2]·H2O 1 and [CuL1Cl2]·2H2O 2, have been synthesized and fully characterized. The structure of complex 1 has been elucidated by a single crystal X-ray diffraction study: the zinc atom is pentacoordinate and the coordination geometry is a distorted square base pyramid, with a geometric structural parameter ? equal to 0.149. Vibrational spectroscopy and ab initio DFT calculations of both compounds have confirmed that the two complexes exhibit similar structures. Full assignment of the vibrational spectra was also supported by careful analysis of the distorted geometries generated by the normal modes

  2. Preferential killing of glucose-depleted HeLa cells by menadione and hyperthermia.

    PubMed

    Kim, J H; Kim, S H; Dutta, P; Pinto, J

    1992-01-01

    Energy deprivation of cancer cells increases sensitivity to killing by hyperthermia. Recent cell culture studies suggest that certain naphthoquinones, especially menadione (vitamin K3), have anti-tumour activity by interfering with the energy metabolism of cells, resulting in the inhibition of aerobic glycolysis. We therefore studied the cytotoxic effects of menadione in HeLa cells in combination with hyperthermia. The cell culture data show that the cytotoxicity is markedly increased in cells deprived of glucose in the medium at 37 degrees C after exposure to menadione. When cells were exposed to menadione (20-40 microM) and hyperthermia (41-42 degrees C), there was a dramatic potentiation of heat-induced cytotoxicity in cells deprived of glucose in the medium. These data suggest that glucose-deficient cancer cells could be selectively killed by the combined treatment of menadione and mild hyperthermia, both of which can be readily achievable in humans. PMID:1545160

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

    SciTech Connect

    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

    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.

  4. Polycyclic aromatic hydrocarbons and their quinones modulate the metabolic profile and induce DNA damage in human alveolar and bronchiolar cells.

    PubMed

    Gurbani, Deepak; Bharti, Santosh Kumar; Kumar, Ashutosh; Pandey, Alok K; Ana, Godson R E E; Verma, Ambrish; Khan, Altaf Husain; Patel, Devendra K; Mudiam, M K R; Jain, Swatantra K; Roy, Raja; Dhawan, Alok

    2013-08-01

    The release of particulate pollutants into the air through burning of coal, crude oil, diesel, coal tar, etc. raises concerns of potential health hazards to the exposed human population. Polycyclic aromatic hydrocarbons (PAHs) are major toxic constituents of particulate matter (PM), which upon ingestion get metabolized to even more toxic metabolites such as quinones. The PAHs levels were assessed in both respirable particulate matter (RSPM, <10?M size) and suspended particulate matter (SPM, >10?M size) of urban ambient air (UAA) and that of major contributors viz. diesel exhaust particles (DEPs) and coal tar combustions emissions (CTCE). Seven US Environmental Protection Agency (USEPA) prioritized PAHs in RSPM and 10 in SPM were detected in UAA. Ten and 15 prioritized PAHs, respectively, were also detected in diesel exhaust particles (DEP) and coal tar combustion emission (CTCE) evidencing their release in the air. These PM associated PAHs for UAA, DEP and CTCE showed significant increase (p<0.05) in mutagenicity and mammalian genotoxicity in the order CTCE>DEP>UAA. Human lung alveolar (A549) and bronchiolar (BEAS-2B) cells when treated with PAH-metabolites viz. 1,4-benzoquinone (1,4-BQ), hydroquinone (HQ), 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ) and 9,10-phenanthroquinone (9,10-PQ) showed metabolic modulation in these cell lines with significant depletion of principal cellular metabolites viz. NADP, uracil, asparagines, glutamine, and histidine and accumulation of di-methyl amine and beta-hydroxybutyrate, identified using (1)H NMR spectroscopy. These results suggest that PAH-quinones induce genotoxic effects by modulating the metabolic machinery inside the cells by a combined effect of oxidative stress and energy depletion. Our data for metabolic profiling of human lung cells could also help in understanding the mechanism of toxicity of other xenobiotics. PMID:23735462

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

    PubMed

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

    2013-06-01

    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

  6. Profiling the NIH Small Molecule Repository for Compounds That Generate H2O2 by Redox Cycling in Reducing Environments

    PubMed Central

    2010-01-01

    We have screened the Library of Pharmacologically Active Compounds (LOPAC) and the National Institutes of Health (NIH) Small Molecule Repository (SMR) libraries in a horseradish peroxidase–phenol red (HRP-PR) H2O2 detection assay to identify redox cycling compounds (RCCs) capable of generating H2O2 in buffers containing dithiothreitol (DTT). Two RCCs were identified in the LOPAC set, the ortho-naphthoquinone ?-lapachone and the para-naphthoquinone NSC 95397. Thirty-seven (0.02%) concentration-dependent RCCs were identified from 195,826 compounds in the NIH SMR library; 3 singleton structures, 9 ortho-quinones, 2 para-quinones, 4 pyrimidotriazinediones, 15 arylsulfonamides, 2 nitrothiophene-2-carboxylates, and 2 tolyl hydrazides. Sixty percent of the ortho-quinones and 80% of the pyrimidotriazinediones in the library were confirmed as RCCs. In contrast, only 3.9% of the para-quinones were confirmed as RCCs. Fifteen of the 251 arylsulfonamides in the library were confirmed as RCCs, and since we screened 17,868 compounds with a sulfonamide functional group we conclude that the redox cycling activity of the arylsulfonamide RCCs is due to peripheral reactive enone, aromatic, or heterocyclic functions. Cross-target queries of the University of Pittsburgh Drug Discovery Institute (UPDDI) and PubChem databases revealed that the RCCs exhibited promiscuous bioactivity profiles and have populated both screening databases with significantly higher numbers of active flags than non-RCCs. RCCs were promiscuously active against protein targets known to be susceptible to oxidation, but were also active in cell growth inhibition assays, and against other targets thought to be insensitive to oxidation. Profiling compound libraries or the hits from screening campaigns in the HRP-PR H2O2 detection assay significantly reduce the timelines and resources required to identify and eliminate promiscuous nuisance RCCs from the candidates for lead optimization. PMID:20070233

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

    PubMed

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

    2012-12-01

    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

  8. [Tobacco--once a medicinal plant. Does it contain substances with medicinal properties?].

    PubMed

    Budzianowski, Jaromir

    2013-01-01

    Tobacco and its use was discovered by Christopher Columbus in parallel with the discovery of America. Soon after, tobacco became a known medicinal plant in Europe. Its harmful effects were gradually discovered, especially those of tobacco smoke, and now it is considered a toxic plant. Tobacco leaf has a monograph in German "Hagers Enzyklopädie derArzneistoffe und Drogen", which describes its old, already not valid, medicinal use and clearly shows the toxic effects. Epidemiological studies indicate about 50% lower incidence of Parkinson's disease in smokers than in non-smokers. In turn, studies of the brains of smokers using positron emission tomography showed significantly decreased level of monoamine oxidase B--an enzyme which degrades dopamine--the neurotransmitter which the significant insufficiency of about 80-85%, is responsible for the symptoms of Parkinson's disease. From the tobacco leaves there were isolated MAO-B inhibitors--naphthoquinone--2,3,6-trimethyl-1,4-naphthoquinone and diterpenoid -trans,trans-farnesol, which occur also in tobacco smoke. In the last decade many papers have appeared on the neuroprotective activity of nicotine, the best known component of tobacco. through the effect of this compound on specific nicotinic cholinergic receptors (nAChRs), which interacts with nigrostriatal dopaminergic system as well as the possibility of using nicotine for the treatment of Parkinson's disease and other neurodegenerative diseases. Moreover, tobacco was also found to contain inhibitors of neuronal nitric oxide synthase (nNOS). Tobacco cannot be considered a medicinal plant, but some compounds occurring in that plant may find therapeutic use. PMID:24501813

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

    NASA Astrophysics Data System (ADS)

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

    2012-08-01

    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.

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

    PubMed Central

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

    2014-01-01

    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

  11. S-nitrosoglutathione covalently modifies cysteine residues of human carbonyl reductase 1 and affects its activity.

    PubMed

    Hartmanová, Tereza; Tambor, Vojt?ch; Len?o, Juraj; Staab-Weijnitz, Claudia A; Maser, Edmund; Wsól, Vladimír

    2013-02-25

    Carbonyl reductase 1 (CBR1 or SDR21C1) is a ubiquitously-expressed, cytosolic, monomeric, and NADPH-dependent enzyme. CBR1 participates in apoptosis, carcinogenesis and drug resistance, and has a protective role in oxidative stress, cancer and neurodegeneration. S-Nitrosoglutathione (GSNO) represents the newest addition to its diverse substrate spectrum, which includes a wide range of xenobiotics and endogenous substances. GSNO has also been shown to covalently modify and inhibit CBR1. The aim of the present study was to quantify and characterize the resulting modifications. Of five candidate cysteines for modification by 2 mM GSNO (positions 26, 122, 150, 226, 227), the last four were analyzed using MALDI-TOF/TOF mass spectrometry and then quantified using the Selected Reaction Monitoring Approach on hyphenated HPLC with a triple quadrupole mass spectrometer. The analysis confirmed GSNO concentration-dependent S-glutathionylation of cysteines at positions 122, 150, 226, 227 which was 2-700 times higher compared to wild-type CBR1 (WT-CBR1). Moreover, a disulfide bond between neighboring Cys-226 and Cys-227 was detected. We suggest a role of these two cysteines as a redox-sensitive cysteine pair. The catalytic properties of wild-type and enzyme modified with 2 mM GSNO were also investigated by steady state kinetic experiments with various substrates. GSNO treatment of CBR1 resulted in a 2-5-fold decrease in kcat with menadione, 4-benzoylpyridine, 2,3-hexanedione, daunorubicin and 1,4-naphthoquinone. In contrast, the same treatment increased kcat for substrates containing a 1,2-diketo group in a ring structure (1,2-naphthoquinone, 9,10-phenanthrenequinone, isatin). Except for 9,10-phenanthrenequinone, all changes in kcat were at least in part compensated for by a similar change in Km, overall yielding no drastic changes in catalytic efficiency. The findings indicate that GSNO-induced covalent modification of cysteine residues affects the kinetic mechanism of CBR1 both in terms of substrate binding and turnover rate, probably by covalent modification of Cys-226 and/or Cys-227. PMID:23295225

  12. Two-electron reduction of quinones by rat liver NAD(P)H:quinone oxidoreductase: quantitative structure-activity relationships.

    PubMed

    Anusevicius, Zilvinas; Sarlauskas, Jonas; Cenas, Narimantas

    2002-08-15

    Mammalian NAD(P)H:quinone oxidoreductase (NQO1, DT-diaphorase, EC 1.6.99.2) catalyzes the two-electron reduction of quinones and plays one of the main roles in the bioactivation of quinoidal drugs. In order to understand the enzyme substrate specificity, we have examined the reactions of rat NQO1 with a number of quinones with available potentials of single-electron (E(1)(7)) reduction and pK(a) of their semiquinones. The hydride transfer potentials (E(7)(H(-))) were calculated from the midpoint potentials of quinones and pK(a) of hydroquinones. Our findings imply that benzo- and naphthoquinones with a van der Waals volume (VdWvol) < or = 200 A(3) are much more reactive than glutathionyl-substituted naphthoquinones, polycyclic quinones, and FMN (VdWvol>200 A(3)) with the same reduction potentials. The entropies of activation (DeltaS(not equal)) in the reduction of "fast" oxidants are equal to -84 to -76 J mol(-1) K(-1), whereas in the reduction of "slow" oxidants Delta S(not equal)=-36 to -11 J mol(-1) K(-1). The large negative Delta S(not equal) in the reduction of fast oxidants may be explained by their better electronic coupling with reduced FAD or the formation of charge-transfer complexes, since fast oxidants bind at the dicumarol binding site, whereas the binding of some slow oxidants outside it has been demonstrated. The reactivity of quinones may be equally well described in terms of the three-step (e(-),H(+),e(-)) hydride transfer, using E(1)(7), pK(a)(QH*), and VdWvol as correlation parameters, or in terms of single-step (H(-)) hydride transfer, using E(7)(H(-)) and VdWvol in the correlation. The analysis of NQO1 reactions with single-electron acceptors and quinones using an "outer-sphere" electron transfer model points to the possibility of a three-step hydride transfer. PMID:12147263

  13. Valence-state analysis through spectroelectrochemistry in a series of quinonoid-bridged diruthenium complexes [(acac)(2)Ru(mu-L)Ru(acac)(2)](n) (n=+2, +1, 0, -1, -2).

    PubMed

    Ghumaan, Sandeep; Sarkar, Biprajit; Maji, Somnath; Puranik, Vedavati G; Fiedler, Jan; Urbanos, Francisco A; Jimenez-Aparicio, Reyes; Kaim, Wolfgang; Lahiri, Goutam Kumar

    2008-01-01

    The quinonoid ligand-bridged diruthenium compounds [(acac)(2)Ru(mu-L(2-))Ru(acac)(2)] (acac(-)=acetylacetonato=2,4-pentanedionato; L(2-)=2,5-dioxido-1,4-benzoquinone, 1; 3,6-dichloro-2,5-dioxido-1,4-benzoquinone, 2; 5,8-dioxido-1,4-naphthoquinone, 3; 2,3-dichloro-5,8-dioxido-1,4-naphthoquinone, 4; 1,5-dioxido-9,10-anthraquinone, 5; and 1,5-diimido-9,10-anthraquinone, 6) were prepared and characterized analytically. The crystal structure analysis of 5 in the rac configuration reveals two tris(2,4-pentanedionato)ruthenium moieties with an extended anthracenedione-derived bis(ketoenolate) pi-conjugated bridging ligand. The weakly antiferromagnetically coupled {Ru(III)(mu-L(2-))Ru(III)} configuration in 1-6 exhibits complicated overall magnetic and EPR responses. The simultaneous presence of highly redox-active quinonoid-bridging ligands and of two ruthenium centers capable of adopting the oxidation states +2, +3, and +4 creates a large variety of possible oxidation state combinations. Accordingly, the complexes 1-6 exhibit two reversible one-electron oxidation steps and at least two reversible reduction processes. Shifts to positive potentials were observed on introduction of Cl substituents (1-->2, 3-->4) or through replacement of NH by O (6-->5). The ligand-to-metal charge transfer (LMCT) absorptions in the visible region of the neutral molecules become more intense and shifted to lower energies on stepwise reduction with two electrons. On oxidation, the para-substituted systems 1-4 exhibit monocation intermediates with intervalence charge transfer (IVCT) transitions of Ru(III)Ru(IV) mixed-valent species. In contrast, the differently substituted systems 5 and 6 show no such near infrared (NIR) absorption. While the first reduction steps are thus assigned to largely ligand-centered processes, the oxidation appears to involve metal-ligand delocalized molecular orbitals with variable degrees of mixing. PMID:18924186

  14. In vivo exposure of Dreissena polymorpha mussels to the quinones menadione and lawsone: menadione is more toxic to mussels than lawsone.

    PubMed

    Osman, A M; Rotteveel, S; den Besten, P J; van Noort, P C M

    2004-01-01

    The principal aim of this study was to assess whether the two quinones, menadione (2-methyl-1,4-naphthoquinone) and lawsone (2-hydroxy-1,4-naphthoquinone), elicit differential toxicity in mussels as has been reported for higher organisms. Therefore, the effects of short-term (48 h) and long-term (20 days) exposure of the two quinones at concentrations of 0.56 and 1 mg l(-1) to zebra mussels, Dreissena polymorpha, under laboratory conditions were studied. After the short-term exposure, the specific activities of the two-electron quinone oxidoreductase (DT-diaphorase) and the one-electron catalysing quinone reductases NADPH-cytochrome c reductase and NADH-cytochrome c reductase were determined in the gills and the rest of the soft tissues (soft mussel tissues minus the gills) of both treated and control mussels. At the higher concentrations of menadione and lawsone used, a significant reduction of the activity of NADPH-cytochrome c reductase in the gills and in the rest of the soft mussel tissues (by 33-34% and 31-43%, respectively) was observed. The activities of DT-diaphorase and NADH-cytochrome c reductase were not significantly affected. Interestingly, DT-diaphorase was observed in the gills, an organ requiring protection against antioxidants. Furthermore, a single-cell electrophoretic assay (comet assay) performed with gill cells to assess DNA damage by the quinones did not show any significant difference between the treated and the control organisms. This indicates that the formation of reactive species by the quinone metabolism in vivo in the mussels was possibly suppressed through the concerted action of DT-diaphorase and antioxidant enzymes. The results of in vitro experiments with gill extracts confirmed the protective role of DT-diaphorase. The rate of the two-electron quinone reduction was found to be five times that of the one-electron quinone reduction. The results of the long-term exposure unambiguously demonstrated that in mussels menadione, unlike in higher organisms, is more toxic than lawsone. The lack of detectability of xanthine oxidase in the mussel tissues could explain the comparatively lower toxicity of lawsone in the invertebtrate, lending support to a previous suggestion that xanthine oxidase might be responsible for the mechanism of toxicity of lawsone in higher organisms in vivo. PMID:15052609

  15. Plumbagin induces G2/M arrest, apoptosis, and autophagy via p38 MAPK- and PI3K/Akt/mTOR-mediated pathways in human tongue squamous cell carcinoma cells

    PubMed Central

    Pan, Shu-Ting; Qin, Yiru; Zhou, Zhi-Wei; He, Zhi-Xu; Zhang, Xueji; Yang, Tianxin; Yang, Yin-Xue; Wang, Dong; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2015-01-01

    Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone; PLB), a naturally occurring naphthoquinone isolated from the roots of Plumbaginaceae plants, has been reported to possess anticancer activities in both in vitro and in vivo studies, but the effect of PLB on tongue squamous cell carcinoma (TSCC) is not fully understood. This study aimed to investigate the effects of PLB on cell cycle distribution, apoptosis, and autophagy, and the underlying mechanisms in the human TSCC cell line SCC25. The results have revealed that PLB exerted potent inducing effects on cell cycle arrest, apoptosis, and autophagy in SCC25 cells. PLB arrested SCC25 cells at the G2/M phase in a concentration- and time-dependent manner with a decrease in the expression level of cell division cycle protein 2 homolog (Cdc2) and cyclin B1 and increase in the expression level of p21 Waf1/Cip1, p27 Kip1, and p53 in SCC25 cells. PLB markedly induced apoptosis and autophagy in SCC25 cells. PLB decreased the expression of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) while increasing the expression level of the pro-apoptotic protein Bcl-2-associated X protein (Bax) in SCC25 cells. Furthermore, PLB inhibited phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), glycogen synthase kinase 3? (GSK3?), and p38 mitogen-activated protein kinase (p38 MAPK) pathways as indicated by the alteration in the ratio of phosphorylation level over total protein expression level, contributing to the autophagy inducing effect. In addition, we found that wortmannin (a PI3K inhibitor) and SB202190 (a selective inhibitor of p38 MAPK) strikingly enhanced PLB-induced autophagy in SCC25 cells, suggesting the involvement of PI3K- and p38 MAPK-mediated signaling pathways. Moreover, PLB induced intracellular reactive oxygen species (ROS) generation and this effect was attenuated by l-glutathione (GSH) and n-acetyl-l-cysteine (NAC). Taken together, these results indicate that PLB promotes cellular apoptosis and autophagy in TSCC cells involving p38 MAPK- and PI3K/Akt/mTOR-mediated pathways with contribution from the GSK3? and ROS-mediated pathways. PMID:25834400

  16. Phytochemistry of the carnivorous sundew genus Drosera (Droseraceae) - future perspectives and ethnopharmacological relevance.

    PubMed

    Egan, Paul A; van der Kooy, Frank

    2013-10-01

    Species of the carnivorous genus Drosera L. have long been a source of valuable natural products. The various phytochemicals characteristic of these species, particularly 1,4-naphthoquinones and flavonoids, have contributed to the diverse utilization of sundews in traditional medicine systems worldwide. A growing number of studies have sought to investigate the comparative phytochemistry of Drosera species for improved sources of pharmaceutically important compounds. The outcomes of these studies are here collated, with emergent trends discussed in detail. Important factors which affect production of secondary metabolites in plants are critically examined, such as environmental influences and in vitro culture, and recommendations subsequently presented based on this. Explicitly, the current review aims to i) present an updated, comprehensive listing of the phytochemical constituents of the genus (including quantitative data where available), ii) summarize important factors which may influence the production of phytopharmaceuticals in plants, and iii) recommend guidelines for future research based on the above, including improved standardization and quality control. We have also included a section discussing future perspectives of research on Drosera spp. based on three different research lines i) the potential to produce much needed lead compounds for treatment of tuberculosis, ii) the potential role of anthocyanins in nitrogen transport, and iii) research into 'Natural Deep Eutectic' solvents produced by Drosera spp. in the droplets or 'dew' employed to capture insect prey. PMID:24130022

  17. Analysis of atmospheric concentrations of quinones and polycyclic aromatic hydrocarbons in vapour and particulate phases

    NASA Astrophysics Data System (ADS)

    Delgado-Saborit, Juana Maria; Alam, Mohammed S.; Godri Pollitt, Krystal J.; Stark, Christopher; Harrison, Roy M.

    2013-10-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-09-01

    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.

  19. Cbl-b-regulated extracellular signal-regulated kinase signaling is involved in the shikonin-induced apoptosis of lung cancer cells in vitro

    PubMed Central

    QU, DAN; CHEN, YU; XU, XIAO-MAN; ZHANG, MENG; ZHANG, YI; LI, SHENG-QI

    2015-01-01

    Shikonin (SK), a naturally occurring naphthoquinone, exhibits antitumor activity. However, its precise mechanisms of action are unknown. In the present study, the effects of SK on NCI-H460 human lung cancer cells were investigated. It was found that SK reduced cell viability and induced apoptosis in the NCI-H460 cells. Additionally, SK inhibited extracellular signal-regulated kinase (ERK) activity, which indicates that inhibition of the ERK pathway is probably one of the mechanisms by which SK induced NCI-H460 cell apoptosis. The expression of Cbl-b was significantly increased by treatment with SK for 4 h, and gradually increased to a maximal level at 24 h; the time taken for the upregulation of Cbl-b protein was in accordance to that required for the downregulation of phospho (p)-ERK protein. The Cbl inhibitor Ps341 reversed the SK-induced downregulation of p-ERK and apoptosis of NCI-H460 cells. These results indicate that Cbl-b potentiates the apoptotic action of SK by inhibiting the ERK pathway in lung cancer cells. PMID:25780420

  20. Discovery and Development of Natural Product-derived Chemotherapeutic Agents Based on a Medicinal Chemistry Approach?†

    PubMed Central

    Lee, Kuo-Hsiung

    2010-01-01

    Medicinal plants have long been an excellent source of pharmaceutical agents. Accordingly, the long term objectives of the author's research program are to discover and design new chemotherapeutic agents based on plant-derived compound leads by using a medicinal chemistry approach, which is a combination of chemistry and biology. Different examples of promising bioactive natural products and their synthetic analogs, including sesquiterpene lactones, quassinoids, naphthoquinones, phenylquinolones, dithiophenediones, neo-tanshinlactone, tylophorine, suksdorfin, DCK, and DCP, will be presented with respect to their discovery and preclinical development as potential clinical trial candidates. Research approaches include bioactivity- or mechanism of action-directed isolation and characterization of active compounds, rational drug design-based modification and analog synthesis, as well as structure-activity relationship and mechanism of action studies. Current clinical trials agents discovered by the Natural Products Research Laboratories, University of North Carolina, include bevirimat (dimethyl succinyl betulinic acid), which is now in Phase IIb trials for treating AIDS. Bevirimat is also the first in a new class of HIV drug candidates called “maturation inhibitors”. In addition, an etoposide analog, GL-331, progressed to anticancer Phase II clinical trials, and the curcumin analog JC-9 is in Phase II clinical trials for treating acne and in development for trials against prostate cancer. The discovery and development of these clinical trials candidates will also be discussed. PMID:20187635

  1. Molecular Structure of Urushiol

    NSDL National Science Digital Library

    2006-04-19

    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.

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

    PubMed Central

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

    2012-01-01

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

  3. Rhinacanthin C Inhibits Osteoclast Differentiation and Bone Resorption: Roles of TRAF6/TAK1/MAPKs/NF-?B/NFATc1 Signaling

    PubMed Central

    Tomomura, Mineko; Suzuki, Ryuichiro; Shirataki, Yoshiaki; Sakagami, Hiroshi; Tamura, Nobuaki; Tomomura, Akito

    2015-01-01

    Rhinacanthin C is a naphthoquinone ester with anti-inflammatory activity, found in Rhinacanthus nasutus (L) Kurz (Acanthaceae). We found that rhinacanthin C inhibited osteoclast differentiation stimulated by the receptor activator of nuclear factor-?B ligand (RANKL) in mouse bone marrow macrophage cultures, although the precise molecular mechanisms underlying this phenomenon are unclear. In this study, we investigated the inhibitory mechanisms of rhinacanthin C in osteoclastogenesis. Rhinacanthin C suppressed RANKL-induced nuclear factor of activated T cells c1 (NFATc1) expression. Phosphorylation of ERK, JNK, and NF-?B, but not p38, was inhibited by rhinacanthin C, which also inhibited RANKL-stimulated TRAF6-TAK1 complex formation. Thus, the anti-osteoclastogenic effect of rhinacanthin C is mediated by a cascade of inhibition of RANKL-induced TRAF6-TAK1 association followed by activation of MAPKs/NF-?B; this leads to suppression of c-Fos and NFATc1, which regulate transcription of genes associated with osteoclast differentiation. In vivo, rhinacanthin C also reduced RANKL-induced osteoclast formation and bone resorption in mouse calvaria. Rhinacanthin C also suppressed LPS-stimulated osteoclastogenesis and bone resorption in vitro and in vivo. Rhinacanthin C may provide a novel therapy for abnormal bone lysis that occurs during inflammatory bone resorption. PMID:26083531

  4. Antiallergic effects of pigments isolated from green sea urchin (Strongylocentrotus droebachiensis) shells.

    PubMed

    Pozharitskaya, Olga N; Shikov, Alexander N; Makarova, Marina N; Ivanova, Svetlana A; Kosman, Vera M; Makarov, Valery G; Bazgier, Václav; Berka, Karel; Otyepka, Michal; Ulrichová, Jitka

    2013-12-01

    This study was undertaken to evaluate possible antiallergic effects of an extract of pigments from green sea urchin (Strongylocentrotus droebachiensis) shells. Effects were studied on animal models - guinea pig ileum contraction, rabbit eyes allergic conjunctivitis, and rabbit local skin irritation. The extract significantly reduced, in a dose-dependent manner, the histamine-induced contractions of the isolated guinea pig ileum with ID50 =1.2 µg/mL (in equivalents of spinochrome B), had an inhibitory effect on the model of ocular allergic inflammation surpassing the reference drug olopatadine, and did not show any irritating effect in rabbits. The extract predominantly contained polyhydroxy-1,4-naphthoquinone which would be responsible for the pharmacological activity. The active compounds of the extract were evaluated in silico with molecular docking. Molecular docking into H1R receptor structures obtained from molecular dynamic simulations showed that all spinochrome derivatives bind to the receptor active site, but spinochrome monomers fit better to it. The results of the present study suggest possibilities for the development of new agents for treating allergic diseases on the base of pigments from sea urchins shells. PMID:24288292

  5. A receptor-interacting protein 1 (RIP1)-independent necrotic death under the control of protein phosphatase PP2A that involves the reorganization of actin cytoskeleton and the action of cofilin-1.

    PubMed

    Tomasella, Andrea; Blangy, Anne; Brancolini, Claudio

    2014-09-12

    Cell death by necrosis is emerging not merely as a passive phenomenon but as a cell-regulated process. Here, by using different necrotic triggers, we prove the existence of two distinct necrotic pathways. The mitochondrial reactive oxygen species generator 2,3-dimethoxy-1,4-naphthoquinone elicits necrosis characterized by the involvement of RIP1 and Drp1. However, G5, a non-selective isopeptidase inhibitor, triggers a distinct necrotic pathway that depends on the protein phosphatase PP2A and the actin cytoskeleton. PP2A catalytic subunit is stabilized by G5 treatment, and its activity is increased. Furthermore, PP2Ac accumulates into the cytoplasm during necrosis similarly to HMGB1. We have also defined in the actin-binding protein cofilin-1 a link between PP2A, actin cytoskeleton, and necrotic death. Cofilin-1-severing/depolymerization activity is negatively regulated by phosphorylation of serine 3. PP2A contributes to the dephosphorylation of serine 3 elicited by G5. Finally, a cofilin mutant that mimics phosphorylated Ser-3 can partially rescue necrosis in response to G5. PMID:25096578

  6. Menaquinone Analogs Inhibit Growth of Bacterial Pathogens

    PubMed Central

    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.

    2013-01-01

    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

  7. Menaquinone analogs inhibit growth of bacterial pathogens.

    PubMed

    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

    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

  8. 2-Sulfanylidene-1,3-dithiolo[4,5-b]naphtho-[2,3-e][1,4]dithiine-5,10-dione.

    PubMed

    Méndez-Rojas, Miguel Angel; Bernès, Sylvain; Pérez-Benítez, Aarón; Romero Zarazúa, María Fernanda; Castellanos-Uribe, Adrián

    2011-11-01

    The title mol-ecule, C(13)H(4)O(2)S(5), is folded by 47.83?(6)° along the S?S vector of the [1,4]dithiine six-membered ring, with the naphtho-quinone and [1,3]dithiole-2-thione moieties being nearly planar [largest deviations from least-squares planes = 0.028?(2) and 0.016?(1)?Å, respectively]. This boat conformation is close to that observed in the analogous compound [Mendez-Rojas et al. (2001). J. Chem. Crystallogr.31, 17-28] including a 2-oxo group [folding angle: 42.3?(1)° at 213?(2)?K]. Both compounds are indeed isomorphous, and the small difference in the folding angle probably results from the involvement of the thioxo group of the title compound in inter-molecular S?S contacts [3.5761?(13)?Å]. In the crystal structure, mol-ecules are stacked in the [100] direction, with dithiole rings making ?-? inter-actions. In a stack, alternating short and long separations are observed between the centroids of dithiole rings, 3.5254?(17) and 4.7010?(18)?Å. PMID:22219881

  9. 2-Sulfanylidene-1,3-dithiolo[4,5-b]naphtho­[2,3-e][1,4]dithiine-5,10-dione

    PubMed Central

    Méndez-Rojas, Miguel Angel; Bernès, Sylvain; Pérez-Benítez, Aarón; Romero Zarazúa, María Fernanda; Castellanos-Uribe, Adrián

    2011-01-01

    The title mol­ecule, C13H4O2S5, is folded by 47.83?(6)° along the S?S vector of the [1,4]dithiine six-membered ring, with the naphtho­quinone and [1,3]dithiole-2-thione moieties being nearly planar [largest deviations from least-squares planes = 0.028?(2) and 0.016?(1)?Å, respectively]. This boat conformation is close to that observed in the analogous compound [Mendez-Rojas et al. (2001). J. Chem. Crystallogr. 31, 17–28] including a 2-oxo group [folding angle: 42.3?(1)° at 213?(2)?K]. Both compounds are indeed isomorphous, and the small difference in the folding angle probably results from the involvement of the thioxo group of the title compound in inter­molecular S?S contacts [3.5761?(13)?Å]. In the crystal structure, mol­ecules are stacked in the [100] direction, with dithiole rings making ?–? inter­actions. In a stack, alternating short and long separations are observed between the centroids of dithiole rings, 3.5254?(17) and 4.7010?(18)?Å. PMID:22219881

  10. Carbonyl reductase activity exhibited by pig testicular 20 beta-hydroxysteroid dehydrogenase.

    PubMed

    Nakajin, S; Tamura, F; Takase, N; Toyoshima, S

    1997-11-01

    The carbonyl reductase activity exhibited by pig testicular 20 beta-hydroxysteroid dehydrogenase (20 beta-HSD) was examined using a recombinant enzyme. Kinetic parameters were obtained for 48 carbonyl group-containing substrates, including aromatic aldehydes, aromatic ketones, cycloketones, quinones, aliphatic aldehydes and aliphatic ketones. 20 beta-HSD showed a high affinity towards quinones, such as 9,10-phenanthrenequinone, alpha-naphthoquinone and menadione (Km values of 4, 2 and 5 microM, respectively), and the substrate utilization efficiency (Vmax/Km) of the enzyme against these quinones was very high. Cyclohexanone and 2-methylcyclohexanone were also reduced with a high Vmax/Km value, but not cyclopentanone or 2-methylcyclopentanone. Various aromatic aldehydes and ketones including benzaldehyde- and acetophenone-derivatives were reduced by 20 beta-HSD. Especially, 4-nitrobenzaldehyde and 4-nitroacetophenone were reduced with high Vmax/Km values in the related compounds. The enzyme also reduced the pyridine-derivatives, 2-, 3-, and 4-benzoylpyridine, with the Vmax/Km value for 2-benzoylpyridine being the highest. 20 beta-HSD reduced aliphatic aldehydes and aliphatic ketones, but was more effective on the former. The correlation between the structure of carbonyl compounds and their substrate Vmax/Km is discussed. PMID:9401736

  11. Microbial fuel cell using anaerobic respiration as an anodic reaction and biomineralized manganese as a cathodic reactant.

    PubMed

    Rhoads, Allison; Beyenal, Haluk; Lewandowski, Zbigniew

    2005-06-15

    We have operated a microbial fuel cell in which glucose was oxidized by Klebsiella pneumoniae in the anodic compartment, and biomineralized manganese oxides, deposited by Leptothrix discophora, were electrochemically reduced in the cathodic compartment. In the anodic compartment, to facilitate the electron transfer from glucose to the graphite electrode, we added a redox mediator, 2-hydroxy-1,4-naphthoquinone. We did not add any redox mediator to the cathodic compartment because the biomineralized manganese oxides were deposited on the surface of a graphite electrode and were reduced directly by electrons from the electrode. We have demonstrated that biomineralized manganese oxides are superiorto oxygen when used as cathodic reactants in microbial fuel cells. The current density delivered by using biomineralized manganese oxides as the cathodic reactant was almost 2 orders of magnitude higher than that delivered using oxygen. Several fuel cells were operated for 500 h, reaching anodic potentials of -441.5 +/- 31 mVscE and cathodic potentials of +384.5 +/- 64 mVscE. When the electrodes were connected by a 50 Ohms resistor, the fuel cell delivered the peak power density of 126.7 +/- 31.5 mW/m2. PMID:16047807

  12. YNL134C from Saccharomyces cerevisiae encodes a novel protein with aldehyde reductase activity for detoxification of furfural derived from lignocellulosic biomass.

    PubMed

    Zhao, Xianxian; Tang, Juan; Wang, Xu; Yang, Ruoheng; Zhang, Xiaoping; Gu, Yunfu; Li, Xi; Ma, Menggen

    2015-05-01

    Furfural and 5-hydroxymethylfurfural (HMF) are the two main aldehyde compounds derived from pentoses and hexoses, respectively, during lignocellulosic biomass pretreatment. These two compounds inhibit microbial growth and interfere with subsequent alcohol fermentation. Saccharomyces cerevisiae has the in situ ability to detoxify furfural and HMF to the less toxic 2-furanmethanol (FM) and furan-2,5-dimethanol (FDM), respectively. Herein, we report that an uncharacterized gene, YNL134C, was highly up-regulated under furfural or HMF stress and Yap1p and Msn2/4p transcription factors likely controlled its up-regulated expression. Enzyme activity assays showed that YNL134C is an NADH-dependent aldehyde reductase, which plays a role in detoxification of furfural to FM. However, no NADH- or NADPH-dependent enzyme activity was observed for detoxification of HMF to FDM. This enzyme did not catalyse the reverse reaction of FM to furfural or FDM to HMF. Further studies showed that YNL134C is a broad-substrate aldehyde reductase, which can reduce multiple aldehydes to their corresponding alcohols. Although YNL134C is grouped into the quinone oxidoreductase family, no quinone reductase activity was observed using 1,2-naphthoquinone or 9,10-phenanthrenequinone as a substrate, and phylogenetic analysis indicates that it is genetically distant to quinone reductases. Proteins similar to YNL134C in sequence from S. cerevisiae and other microorganisms were phylogenetically analysed. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25656244

  13. Ability of the oriental fruit moth Grapholita molesta (Lepidoptera: Tortricidae) to detoxify juglone, the main secondary metabolite of the non-host plant walnut.

    PubMed

    Piskorski, Rafal; Ineichen, Simon; Dorn, Silvia

    2011-10-01

    Many plant species produce toxic secondary metabolites that limit attacks by herbivorous insects, and may thereby constrain insect expansion to new hosts. Walnut is a host for the codling moth Cydia pomonella, which efficiently detoxifies the main walnut defensive compound juglone (5-hydroxy-1,4-naphthoquinone). The oriental fruit moth Grapholita molesta, which also belongs to the tribe Grapholitini, does not feed on walnut. We tested the performance of G. molesta, a highly invasive species, on artificial diets containing juglone at levels mimicking those found in walnut over the growing season. Juglone-fed G. molesta survived relatively well to adulthood, but larval and adult body weights were reduced, and larval developmental time was prolonged in a dose-dependent fashion. Chemical analysis of frass from larvae that had been fed a juglone-containing diet suggests that G. molesta reduces juglone to non-toxic 1,4,5-trihydroxynaphthalene in its gut. This unexpected tolerance of G. molesta to high levels of juglone may facilitate expansion of the host range beyond the current rosacean fruit trees used by this invasive pest. PMID:21901444

  14. How the oligophage codling moth Cydia pomonella survives on walnut despite its secondary metabolite juglone.

    PubMed

    Piskorski, Rafal; Dorn, Silvia

    2011-06-01

    Besides apple, its primary host, the codling moth Cydia pomonella uses walnut as a secondary host. Abundance of toxic naphthoquinones, among which juglone prevails, does not restrain this economically important pest insect from infesting walnut, but processes underlying the suitability of this host were yet unknown. Larvae feeding on an artificial diet supplemented with juglone at naturally occurring concentrations survived to adulthood at a similarly high proportion as those in the juglone-devoid control. However, their development time was prolonged, their weight gain was reduced, and adult sex ratio was distorted. Results from the natural system with walnut and apple fruits were in line with data gained on artificial diet. Remarkably, a twofold increase of the maximal juglone content reported from the walnut husk was lethal to the larvae. Chemical analyses showed that larvae feeding on the artificial diet supplemented with juglone concentrations present in walnut contained 1,4,5-trihydroxynaphthalene and excreted it in their frass, whereas the hemolymph contained neither detectable amounts of juglone nor the product of its reduction. Hence, effective metabolism of juglone in the intestinal system of the larvae underlies their survival on host plants containing this defensive compound. PMID:21356213

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

    PubMed

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

    2002-03-01

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

  16. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts

    PubMed Central

    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

    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. PMID:23812755

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

    PubMed

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

    2014-08-01

    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

  18. 2-Phenylaminonaphthoquinones and related compounds: synthesis, trypanocidal and cytotoxic activities.

    PubMed

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

    2014-09-01

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

  19. The organotelluride catalyst (PHTE)?NQ prevents HOCl-induced systemic sclerosis in mouse.

    PubMed

    Marut, Wioleta K; Kavian, Niloufar; Servettaz, Amélie; Nicco, Carole; Ba, Lalla A; Doering, Mandy; Chéreau, Christiane; Jacob, Claus; Weill, Bernard; Batteux, Frédéric

    2012-04-01

    Systemic sclerosis (SSc) is a connective tissue disorder characterized by skin and visceral fibrosis, microvascular damage, and autoimmunity. HOCl-induced mouse SSc is a murine model that mimics the main features of the human disease, especially the activation and hyperproliferation rate of skin fibroblasts. We demonstrate here the efficiency of a tellurium-based catalyst 2,3-bis(phenyltellanyl)naphthoquinone ((PHTE)(2)NQ) in the treatment of murine SSc, through its selective cytotoxic effects on activated SSc skin fibroblasts. SSc mice treated with (PHTE)(2)NQ displayed a significant decrease in lung and skin fibrosis and in alpha-smooth muscle actin (?-SMA) expression in the skin compared with untreated mouse SSc animals. Serum concentrations of advanced oxidation protein products, nitrate, and anti-DNA topoisomerase I autoantibodies were increased in SSc mice, but were significantly reduced in SSc mice treated with (PHTE)(2)NQ. To assess the mechanism of action of (PHTE)(2)NQ, the cytotoxic effect of (PHTE)(2)NQ was compared in normal fibroblasts and in mouse SSc skin fibroblasts. ROS production is higher in mouse SSc fibroblasts than in normal fibroblasts, and was still increased by (PHTE)(2)NQ to reach a lethal threshold and kill mouse SSc fibroblasts. Therefore, the effectiveness of (PHTE)(2)NQ in the treatment of mouse SSc seems to be linked to the selective pro-oxidative and cytotoxic effects of (PHTE)(2)NQ on hyperproliferative fibroblasts. PMID:22277946

  20. Redox reactions of the FAD-containing apoptosis-inducing factor (AIF) with quinoidal xenobiotics: a mechanistic study

    PubMed Central

    Misevi?ien?, Lina; Anusevi?ius, Žilvinas; Šarlauskas, Jonas; Sevrioukova, Irina F.; ??nas, Narimantas

    2011-01-01

    Mitochondrial apoptosis-inducing factor (AIF) is a FAD-containing protein that under certain conditions translocates to the nucleus and causes a programmed cell death, apoptosis. The apoptogenic action of AIF is redox controlled as the NADH-reduced AIF dimer has lower affinity for DNA than the oxidized monomer. To gain further insights into the mechanism of AIF, we investigated its interaction with a series of quinone oxidants, including a number of anticancer quinones. Our data indicate that the NADH:quinone oxidoreduction catalyzed by AIF follows a “ping-pong” scheme, with the reductive half-reaction being rate-limiting and the FADH--NAD+ charge-transfer complex serving as an electron donor. AIF is equally reactive toward benzo- and naphthoquinones, but may discriminate structures with a higher number of aromatic rings. The reactivity of quinones is mainly defined by their one-electron reduction potential, whereas the size and nature of the substituents play a minor role. AIF is unlikely to significantly contribute to bioreductive activation of low-potential quinoidal anticancer quinones. However, high-potential quinones, e.g. a toxic natural compound naphthazarin, maintain AIF in the oxidized state when a significant excess of NADH is present. Thus, these compounds may prevent the accumulation of the reduced form of AIF in vivo, and enhance AIF-mediated apoptosis. PMID:21664341

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

    PubMed

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

    2013-07-01

    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

  2. Beneficial Effect of Shikonin on Experimental Colitis Induced by Dextran Sulfate Sodium in Balb/C Mice

    PubMed Central

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

    2012-01-01

    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

  3. Conjugated polymer and drug co-encapsulated nanoparticles for chemo- and photo-thermal combination therapy with two-photon regulated fast drug release.

    PubMed

    Yuan, Youyong; Wang, Zuyong; Cai, Pingqiang; Liu, Jie; Liao, Lun-De; Hong, Minghui; Chen, Xiaodong; Thakor, Nitish; Liu, Bin

    2015-02-21

    The spatial-temporal synchronization of photothermal therapy and chemotherapy is highly desirable for an efficient cancer treatment with synergistic effect. Herein, we developed a chemotherapeutic drug doxorubicin (DOX) and photothermal conjugated polymer (CP) co-loaded nanoplatform using a near-infrared (NIR) laser responsive amphiphilic brush copolymer as the encapsulation matrix. The obtained nanoparticles (NPs) exhibit good monodispersity and excellent stability, which can efficiently convert laser energy into thermal energy for photothermal therapy. Moreover, the hydrophobic polymer matrix bearing a number of 2-diazo-1,2-naphthoquinones (DNQ) moieties could be transformed to a hydrophilic one upon NIR two-photon laser irradiation, which leads to fast drug release. Furthermore, the surface modification of the NPs with cyclic arginine-glycine-aspartic acid (cRGD) tripeptide significantly enhances the accumulation of the NPs within integrin ?v?3 overexpressed cancer cells. The half-maximal inhibitory concentration (IC50) of the combination therapy is 13.7 ?g mL(-1), while the IC50 for chemotherapy and photothermal therapy alone is 147.8 ?g mL(-1) and 36.2 ?g mL(-1), respectively. The combination index (C.I.) is 0.48 (<1), which indicates the synergistic effect for chemotherapy and PTT. These findings provide an excellent NIR laser regulated nanoplatform for combined cancer treatment with synergistic effect due to the synchronous chemo- and photo-thermal therapy. PMID:25608113

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

    PubMed

    Kang, Ik-Joon; Lee, Mu-Hyoung

    2006-07-01

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

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

    PubMed

    Abiko, Yumi; Kumagai, Yoshito

    2013-07-15

    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

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

    PubMed

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

    2002-05-01

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

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

    PubMed Central

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

    2002-01-01

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

  8. Bioprocessing of lignite coals using reductive microorganisms

    SciTech Connect

    Crawford, D.L.

    1989-01-01

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

  9. Dissimilar effects of ?-lapachone- and hydroxyurea-induced DNA replication stress in root meristem cells of Allium cepa.

    PubMed

    Zabka, Aneta; Trzaskoma, Pawe?; Maszewski, Janusz

    2013-12-01

    Two anticancer drugs, ?-lapachone (?-lap, a naphthoquinone) and hydroxyurea (HU, an inhibitor of ribonucleotide reductase), differently affect nuclear morphology and cell cycle control mechanisms in root meristem cells of Allium cepa. The 18 h treatment with 100 ?M ?-lap results in a lowered number of M-phase cells, increased occurrence of mitotic abnormalities, including over-condensation of chromosomes, their enhanced stickiness, formation of anaphase bridges, micronucleation and reduced mitotic spindles. Following prolonged incubations using high doses of ?-lap, cell nuclei reveal dark-red fluorescence evenly distributed in chromatin surrounding the unstained regions of nucleoli. Both drugs generate H2O2 and induce DNA double strand breaks, which is correlated with ?-phoshorylation of H2AX histones. However, the extent of H2AX phosphorylation (including the frequency of ?-H2AX foci and the relative number cells creating phospho-H2AX domains) is considerably reduced in root meristem cells treated jointly with the ?-lap/HU mixture. Furthermore, various effects of caffeine (an inhibitor of ATM/ATR cell cycle checkpoint kinases) on ?-lap- and HU-induced ?-phoshorylation of H2AX histones and the protective activity of HU against ?-lap suggest that their genotoxic activities are largely dissimilar. ?-Lap treatment results in the induction of apoptosis-like programmed cell death, while HU treatment leads to cell adaptation to replication stress and promotion of abnormal nuclear divisions with biphasic interphase/mitotic states of chromatin condensation. PMID:24184448

  10. Triterpenoids from the roots of Pterospermum heterophyllum Hance.

    PubMed

    Li, Shuai; Shi, Yan; Shang, Xiao-Ya; Cui, Bao-Song; Yuan, Yi; Chen, Xiao-Guang; Yang, Yong-Chun; Shi, Jian-Gong

    2009-07-01

    Two new triterpenoids taraxer-14-ene-1alpha,3beta-diol (1) and 3beta-hydroxytaraxer-14-ene-1-one (2), together with the known triterpenes taraxerol (3), betulin (4), betulinic acid (5), sumaresinolic acid (6), and 5-hydroxy-2-methoxy-1,4-naphthoquinone (7), 5,7-dihydroxy-6,8-dimethylchromone (8), alpha-monpalmitin (9), palmitic acid (10), 6beta-hydroxystigmast-4-en-3-one (11), beta-sitostero1 (12), have been isolated from the petroleum ether fraction of the ethanolic extract of Pterospermum heterophyllum. Their structures were established by spectroscopic methods including IR, MS, 1D, and 2D NMR experiments. Compounds 1-8 were evaluated against several human cancer cell lines. Compound 1 showed in vitro selective cytotoxicity against human lung cancer cell lines (A549) with an IC(50) value of 1.22 microM. Compound 7 showed significant cytotoxicity against the A549, HCT-8, Bel7402, BGC-823, and A2780 cancer cell lines with IC(50) values of 0.21, 0.55, 0.40, 0.59, and 0.34 microM, respectively. However, the other compounds were inactive (IC(50)>10 microM). PMID:20183302

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

    PubMed

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

    2008-02-01

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

  12. Plumbagin Inhibits Prostate Carcinogenesis in Intact and Castrated PTEN Knockout Mice via Targeting PKC?, Stat3, and Epithelial-to-Mesenchymal Transition Markers.

    PubMed

    Hafeez, Bilal Bin; Fischer, Joseph W; Singh, Ashok; Zhong, Weixiong; Mustafa, Ala; Meske, Louise; Sheikhani, Mohammad Ozair; Verma, Ajit Kumar

    2015-05-01

    Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4(+)) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 ppm) inhibits tumor development in intact as well as castrated Pten-KO mice. Plumbagin has shown no signs of toxicity at either of these doses. Plumbagin treatment resulted in a decrease expression of PKC?, AKT, Stat3, and COX2 compared with the control mice. Plumbagin treatment also inhibited the expression of vimentin and slug, the markers of epithelial-to-mesenchymal transition (EMT) in prostate tumors. In summary, the results indicate that dietary plumbagin inhibits growth of both primary and castration-resistant prostate cancer (CRPC) in Pten-KO mice, possibly via inhibition of PKC?, Stat3, AKT, and EMT markers (vimentin and slug), which are linked to the induction and progression of prostate cancer. PMID:25627799

  13. Application of cyclic biamperometry to viability and cytotoxicity assessment in human corneal epithelial cells.

    PubMed

    Rahimi, Mehdi; Youn, Hyun-Yi; McCanna, David J; Sivak, Jacob G; Mikkelsen, Susan R

    2013-05-01

    The application of cyclic biamperometry to viability and cytotoxicity assessments of human corneal epithelial cells has been investigated. Electrochemical measurements have been compared in PBS containing 5.0 mM glucose and minimal essential growth medium. Three different lipophilic mediators including dichlorophenol indophenol, 2-methyl-1,4-naphthoquinone (also called menadione or vitamin K3) and N,N,N',N'-tetramethyl-p-phenylenediamine have been evaluated for shuttling electrons across the cell membrane to the external medium. Transfer of these electrons to ferricyanide in the extra cellular medium results in the accumulation of ferrocyanide. The amount of ferrocyanide is then determined using cyclic biamperometry and is related to the extent of cell metabolic activity and therefore cell viability. To illustrate cytotoxicity assessment of chemicals, hydrogen peroxide, benzalkonium chloride and sodium dodecyl sulfate have been chosen as sample toxins, the cytotoxicities of which have been evaluated and compared to values reported in the literature. Similar values have been reported using colorimetric assays; however, the simplicity of this electrochemical assay can, in principle, open the way to miniaturization onto lab-on-chip devices and its incorporation into tiered-testing approaches for cytotoxicity assessment. PMID:23443523

  14. Harvesting energy from the marine sediment-water interface II. Kinetic activity of anode materials.

    PubMed

    Lowy, Daniel A; Tender, Leonard M; Zeikus, J Gregory; Park, Doo Hyun; Lovley, Derek R

    2006-05-15

    Here, we report a comparative study on the kinetic activity of various anodes of a recently described microbial fuel cell consisting of an anode imbedded in marine sediment and a cathode in overlying seawater. Using plain graphite anodes, it was demonstrated that a significant portion of the anodic current results from oxidation of sediment organic matter catalyzed by microorganisms colonizing the anode and capable of directly reducing the anode without added exogenous electron-transfer mediators. Here, graphite anodes incorporating microbial oxidants are evaluated in the laboratory relative to plain graphite with the goal of increasing power density by increasing current density. Anodes evaluated include graphite modified by adsorption of anthraquinone-1,6-disulfonic acid (AQDS) or 1,4-naphthoquinone (NQ), a graphite-ceramic composite containing Mn2+ and Ni2+, and graphite modified with a graphite paste containing Fe3O4 or Fe3O4 and Ni2+. It was found that these anodes possess between 1.5- and 2.2-fold greater kinetic activity than plain graphite. Fuel cells were deployed in a coastal site near Tuckerton, NJ (USA) that utilized two of these anodes. These fuel cells generated ca. 5-fold greater current density than a previously characterized fuel cell equipped with a plain graphite anode, and operated at the same site. PMID:16574400

  15. PLS-Prediction and Confirmation of Hydrojuglone Glucoside as the Antitrypanosomal Constituent of Juglans Spp.

    PubMed

    Ellendorff, Therese; Brun, Reto; Kaiser, Marcel; Sendker, Jandirk; Schmidt, Thomas J

    2015-01-01

    Naphthoquinones (NQs) occur naturally in a large variety of plants. Several NQs are highly active against protozoans, amongst them the causative pathogens of neglected tropical diseases such as human African trypanosomiasis (sleeping sickness), Chagas disease and leishmaniasis. Prominent NQ-producing plants can be found among Juglans spp. (Juglandaceae) with juglone derivatives as known constituents. In this study, 36 highly variable extracts were prepared from different plant parts of J. regia, J. cinerea and J. nigra. For all extracts, antiprotozoal activity was determined against the protozoans Trypanosoma cruzi, T. brucei rhodesiense and Leishmania donovani. In addition, an LC-MS fingerprint was recorded for each extract. With each extract's fingerprint and the data on in vitro growth inhibitory activity against T. brucei rhodesiense a Partial Least Squares (PLS) regression model was calculated in order to obtain an indication of compounds responsible for the differences in bioactivity between the 36 extracts. By means of PLS, hydrojuglone glucoside was predicted as an active compound against T. brucei and consequently isolated and tested in vitro. In fact, the pure compound showed activity against T. brucei at a significantly lower cytotoxicity towards mammalian cells than established antiprotozoal NQs such as lapachol. PMID:26035104

  16. Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib.

    PubMed

    Zhao, Qiaoli; Kretschmer, Nadine; Bauer, Rudolf; Efferth, Thomas

    2015-09-01

    Overexpression and mutation of the epidermal growth factor receptor (EGFR) gene play a causal role in tumorigenesis and resistance to treatment of glioblastoma (GBM). EGFR inhibitors such as erlotinib are currently used for the treatment of GBM; however, their efficacy has been limited due to drug resistance. New treatment strategies are therefore urgently needed. Shikonin, a natural naphthoquinone, induces both apoptosis and necroptosis in human glioma cells, but the effectiveness of erlotinib-shikonin combination treatment as well as the underlying molecular mechanisms is unknown yet. In this study, we investigated erlotinib in combination with shikonin and 14 shikonin derivatives in parental U87MG and transfected U87MG.?EGFR GBM cells. Most of the shikonin derivatives revealed strong cytotoxicity. Shikonin together with five other derivatives, namely deoxyshikonin, isobutyrylshikonin, acetylshikonin, ?,?-dimethylacrylshikonin and acetylalkannin showed synergistic cytotoxicity toward U87MG.?EGFR in combination with erlotinib. Moreover, the combined cytotoxic effect of shikonin and erlotinib was further confirmed with another three EGFR-expressing cell lines, BS153, A431 and DK-MG. Shikonin not only dose-dependently inhibited EGFR phosphorylation and decreased phosphorylation of EGFR downstream molecules, including AKT, P44/42MAPK and PLC?1, but also together with erlotinib synergistically inhibited ?EGFR phosphorylation in U87MG.?EGFR cells as determined by Loewe additivity and Bliss independence drug interaction models. These results suggest that the combination of erlotinib with shikonin or its derivatives might be a potential strategy to overcome drug resistance to erlotinib. PMID:25688715

  17. Effects of different quinoid redox mediators on the anaerobic reduction of azo dyes by bacteria.

    PubMed

    Rau, Jorg; Knackmuss, Hans-Joachim; Stolz, Andreas

    2002-04-01

    The addition of quinoid redox mediators to anaerobically incubated cultures of various taxonomically different bacterial species resulted in significantly increased reduction rates for the azo dye amaranth. From different quinones tested, generally anthraquinone-2-sulfonate (AQS) and lawsone (2-hydroxy-1,4-naphthoquinone) caused the highest increase in the azoreductase activities. The effects of AQS and lawsone were studied in greater detail with Sphingomonas xenophaga BN6 and Escherichia coli K12. Both strains reduced the quinones under anaerobic conditions with significantly different relative activities. The chemically reduced forms of AQS, lawsone, and different other quinones were assayed for their ability to decolorize amaranth, and a good correlation between the redox potentials of the quinones and the reduction rates of the azo dyes was observed. The addition of AQS or lawsone also increased the ability of unacclimated sewage sludge to reduce azo dyes. Chemically pure lawsone could be replaced by the powdered leaves of the henna plant which contain significant amounts of lawsone. PMID:11999057

  18. Synthesis and cytotoxic activity of metallic complexes of lawsone.

    PubMed

    Oramas-Royo, Sandra; Torrejón, Concepción; Cuadrado, Irene; Hernández-Molina, Rita; Hortelano, Sonsoles; Estévez-Braun, Ana; de Las Heras, Beatriz

    2013-05-01

    In the present study, a series of metallic complexes of the 1,4-naphthoquinone lawsone (2-6) were synthesized and evaluated for potential cytotoxicity in a mouse leukemic macrophagic RAW 264.7 cell line. Cell viability was determined by the MTT assay. Significant growth inhibition was observed for the copper complex (4) with an IC(50) value of 2.5 ?M. This compound was selected for further evaluation of cytotoxic activity on several human cancer cells including HT-29 (human colorectal adenocarcinoma), HepG2 (human hepatocellular carcinoma) and HeLa, (human cervical adenocarcinoma cells). Significant cell viability decrease was also observed in HepG2 cells. The apoptotic potential of this complex was evaluated in these cells. Compound 4 induced apoptosis by a mechanism that involves the activation of caspases 3, 8 and 9 and modulation of apoptotic-related proteins such as Bax, Bad, and p53. These results indicate that metal complexes of lawsone derivatives, in particular compound 4, might be used for the design of new antitumoral agents. PMID:23545136

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

    PubMed Central

    Rau, Jörg; Stolz, Andreas

    2003-01-01

    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. PMID:12788749

  20. Redoxal as a new lead structure for dihydroorotate dehydrogenase inhibitors: a kinetic study of the inhibition mechanism.

    PubMed

    Knecht, W; Löffler, M

    2000-02-01

    Mitochondrial dihydroorotate dehydrogenase (DHOdehase; EC 1.3.99.11) is a target of anti-proliferative, immunosuppressive and anti-parasitic agents. Here, redoxal, (2,2'-[3,3'-dimethoxy[1, 1'-biphenyl]-4,4'-diyl)diimino]bis-benzoic acid, was studied with isolated mitochondria and the purified recombinant human and rat enzyme to find out the mode of kinetic interaction with this target. Its pattern of enzyme inhibition was different from that of cinchoninic, isoxazol and naphthoquinone derivatives and was of a non-competitive type for the human (K(ic)=402 nM; K(iu)=506 nM) and the rat enzyme (K(ic)=116 nM; K(iu)=208 nM). The characteristic species-related inhibition of DHOdehase found with other compounds was less expressed with redoxal. In human and rat mitochondria, redoxal did not inhibit NADH-induced respiration, its effect on succinate-induced respiration was marginal. This was in contrast to the sound effect of atovaquone and dichloroallyl-lawsone, studied here for comparison. In human mitochondria, the IC(50) value for the inhibition of succinate-induced respiration by atovaquone was 6.1 microM and 27.4 microM for the DHO-induced respiration; for dichlorallyl-lawsone, the IC(50) values were 14.1 microM and 0.23 microM. PMID:10664450

  1. Enhancing survival of Escherichia coli by expression of azoreductase AZR possessing quinone reductase activity.

    PubMed

    Liu, Guangfei; Zhou, Jiti; Jin, Ruofei; Zhou, Mi; Wang, Jing; Lu, Hong; Qu, Yuanyuan

    2008-09-01

    Quinone reductase activity of azoreductase AZR from Rhodobacter sphaeroides was reported. High homologies were found in the cofactor/substrate-binding regions of quinone reductases from different domains. 3D structure comparison revealed that AZR shared a common overall topology with mammal NAD(P)H/quinone oxidoreductase NQO1. With menadione as substrate, the optimal pH value and temperature were pH 8-9 and 50 degrees C, respectively. Following the ping-pong kinetics, AZR transferred two electrons from NADPH to quinone substrate. It could reduce naphthoquinones and anthraquinones, such as menadione, lawsone, anthraquinone-2-sulfonate, and anthraquinone-2,6-disulfonate. However, no activity was detected with 1,4-benzoquinone. Dicoumarol competitively inhibited AZR's quinone reductase activity with respect to NADPH, with an obtained K (i) value of 87.6 microM. Significantly higher survival rates were obtained in Escherichia coli YB overexpressing AZR than in the control strain when treated by heat shock and oxidative stressors such as H(2)O(2) and menadione. PMID:18548247

  2. Oxygen-insensitive nitroreductases NfsA and NfsB of Escherichia coli function under anaerobic conditions as lawsone-dependent Azo reductases.

    PubMed

    Rau, Jörg; Stolz, Andreas

    2003-06-01

    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. PMID:12788749

  3. Enhanced dechlorination of carbon tetrachloride by Geobacter sulfurreducens in the presence of naturally occurring quinones and ferrihydrite.

    PubMed

    Doong, Ruey-an; Lee, Chun-chi; Lien, Chia-min

    2014-02-01

    The effect of naturally occurring quinones including lawsone (LQ), ubiquinone (UQ), juglone (JQ), and 1,4-naphthoquinone (NQ) on the biotransformation of carbon tetrachloride (CT) in the presence of Geobacter sulfurreducens and ferrihydrite was investigated. AQDS was used as the model compound for comparison. The reductive dissolution of ferrihydrite by G. sulfurreducens was enhanced by AQDS, NQ, and LQ. However, addition of UQ and JQ had little enhancement effect on Fe(II) production. The bioreduction efficiency and rate of ferrihydrite was highly dependent on the natural property and concentration of quinone compounds and the addition of low concentrations of LQ and NQ significantly accelerated the biotransformation rate of CT. The pseudo-first-order rate constants for CT dechlorination (kobsCT) in AQDS-, LQ- and NQ-amended batches were 5.4-5.8, 4.6-7.4 and 2.4-5.8 times, respectively, higher than those in the absence of quinone. A good relationship between kobsCT for CT dechlorination and bioreduction ratio of ferrihydrite was observed, indicating the important role of biogenic Fe(II) in dechlorination of CT under iron-reducing conditions. Spectroscopic analysis showed that AQDS and NQ could be reduced to semiquinones and hydroquinones, while only hydroquinones were generated in LQ-amended batches. PMID:24290294

  4. Cobalt lawsone complexes: searching for new valence tautomers.

    PubMed

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

    2013-04-21

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

  5. Structure-activity relationships of anthraquinones on the suppression of DNA-binding activity of the aryl hydrocarbon receptor induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed

    Fukuda, Itsuko; Kaneko, Atsushi; Nishiumi, Shin; Kawase, Masaya; Nishikiori, Rika; Fujitake, Nobuhide; Ashida, Hitoshi

    2009-03-01

    Anthraquinones are widely present in plant kingdom, and clinically used as laxatives. Environmental contaminants, dioxins, develop various adverse effects through transformation of a cytosolic aryl hydrocarbon receptor (AhR). We investigated the effects of 18 anthraquinones and 7 of their structurally related compounds on transformation of the AhR estimated by its DNA-binding activity in the cell-free system. 1,4-Dihydroxyanthraquinone (quinizarin), 1,5-dihydroxyanthraquinone (anthrarufin), 1,8-dihydroxyanthraquinone (danthron), and 5-hydroxy-1,4-naphthoquinone (juglone) strongly suppressed DNA-binding activity of the AhR induced by 0.1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with their IC(50) values around 1 muM. On the other hand, anthraquinone, 2,6-dihydroxyanthraquinone (anthraflavic acid), and 2-hydroxy-1,4-naphthalendione (lawsone) showed moderate effects. Quantitative structure-activity relationships analysis demonstrated that hydroxyl groups at C1 or C4 but not C3 position of anthraquinone structure are critical for the suppressive effects. In addition, all compounds except lawsone had no agonistic effect. The suppressive effects of anthraquinones in a cultured cell system were also confirmed. In human hepatoma HepG2 cells, chrysophanol, danthron, and rhein also suppressed the DNA-binding activity in a dose-dependent manner, although aloe-emodin showed a moderate effect. The findings of this study may be useful for the design of the novel antagonists of the AhR. PMID:19269596

  6. Inhibition of apoptosis by menadione on exposure to UVA.

    PubMed

    Ibuki, Y; Toyooka, T; Goto, R

    2006-09-01

    Quinones are widely distributed in the environment, both as natural products and as pollutants. This paper reports that one of the simplest quinones, 2-methyl-1,4-naphthoquinone (menadione), effectively inhibited apoptosis in the presence of UVA. Menadione suppressed the apoptosis induced by serum depletion and cell detachment. This effect was significantly enhanced by UVA irradiation. An antioxidant, N-acetylcysteine, completely inhibited the antiapoptotic effects of both menadione itself and menadione plus UVA, and peroxidation of the cells after treatment was observed using a probe to detect the intracellular production of peroxides. By contrast, 2-hydroxy-1,4-naphtoquinone (lawsone) showed no antiapoptotic effect in the presence or absence of UVA. Lawsone is reported not to undergo the redox process that produces reactive oxygen species. These results indicated that intracellular peroxidation contributed to the antiapoptotic effects of both menadione itself and menadione plus UVA. Dysregulation of the apoptotic process is critical to carcinogenesis. The photosensitization of quinone compounds as it relates to the inhibition of apoptosis should be examined in the future. PMID:16845610

  7. Effect of quinoid redox mediators on the aerobic decolorization of azo dyes by cells and cell extracts from Escherichia coli.

    PubMed

    Cui, Daizong; Li, Guofang; Zhao, Dan; Zhao, Min

    2015-03-01

    It is widely accepted that the addition of redox mediators increases the decolorization rates of azo dyes by bacterial strains under anaerobic conditions. However, little information exists about whether quinoid redox mediators can enhance the performance of aerobic azo dye decolorization. In the present study, quinone-mediated decolorization of different azo dyes by whole cells and cell extracts from the Escherichia coli strain CD-2 under aerobic conditions were investigated. The results demonstrated that reduction rates of different azo dyes were greatly increased when quinone compounds were used as redox mediators. Compared with menadione, 2-hydroxy-1,4-naphthoquinone (lawsone) was more effective at aiding azo dye degradation and the optimum concentration for lawsone is 0.1 mM. Strain CD-2 and the anthraquinone were co-immobilized by entrapment in different polymeric matrices. The co-immobilized beads exhibited good catalytic activity for azo dye degradation and kept stable during successive repeated experiments. The mechanism of the quinone-mediated reduction showed that although whole cells incubated with quinones could significantly increase the rate of decolorization of azo dyes, the quinone compounds did not directly promote azoreductase activity. According to the survey, this is the first report to confirm that the addition of quinoid redox mediators to bacteria increased decolorization under aerobic conditions. PMID:25323408

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

    PubMed

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

    2002-09-01

    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

  9. Enhanced anaerobic degradation of polymeric azo compounds by Escherichia coli in the presence of low-molecular-weight redox mediators.

    PubMed

    Rau, J; Maris, B; Kinget, R; Samyn, C; Van Den Mooter, G; Stolz, A

    2002-11-01

    The effects of the redox mediator lawsone (2-hydroxy-1,4-naphthoquinone) on the ability of Escherichia coli to reduce anaerobically polymeric azo compounds were analysed. Two types of polymeric azo compounds were tested, that have been proposed as putative tools for the site-specific targeting of drugs to the colon. The first group of polymers consisted basically of linear chains of polymethacrylic acid or polymethylmethacrylate which were interrupted by subunits of 4,4'-bis(methacryloylamino)azobenzene. These polymers differed significantly in their hydrophilicity according to the relative proportion of polymethacrylic acid used for the polymerization procedure. The second group of polymers consisted of almost water-insoluble poly(ether-ester)azo polymers that were composed of 4-(6-hydroxyhexyl)oxy-phenylazobenzoate and 16-hydroxyhexadecanoate. The addition of lawsone to the anaerobically incubated cultures of E. coli resulted in a pronounced increase in the reduction rates of the water-soluble poly(methacrylate-co-4,4'-bis(methacryloylamino)azobenzene) and in a much smaller, but significant, increase in the reduction rates of the hydrophobic poly(ether-ester)azo polymers. An increase in the amount of azo groups resulted, for the hydrophobic poly(ether-ester)azo polymers, in an increased reduction rate in the presence of the redox mediator lawsone. PMID:12495549

  10. Screening of Potential anti-Trypanosoma cruzi Candidates: In Vitro and In Vivo Studies

    PubMed Central

    Soeiro, Maria de Nazaré C; de Castro, Solange Lisboa

    2011-01-01

    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. PMID:21629508

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

    PubMed

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

    2012-03-01

    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

  12. Reduction of chalcogen oxyanions and generation of nanoprecipitates by the photosynthetic bacterium Rhodobacter capsulatus.

    PubMed

    Borghese, Roberto; Baccolini, Chiara; Francia, Francesco; Sabatino, Piera; Turner, Raymond J; Zannoni, Davide

    2014-03-30

    The facultative photosynthetic bacterium Rhodobacter capsulatus is characterized in its interaction with the toxic oxyanions tellurite (Te(IV)) and selenite (Se(IV)) by a highly variable level of resistance that is dependent on the growth mode making this bacterium an ideal organism for the study of the microbial interaction with chalcogens. As we have reported in the past, while the oxyanion tellurite is taken up by R. capsulatus cells via acetate permease and it is reduced to Te(0) in the cytoplasm in the form of splinter-like black intracellular deposits no clear mechanism was described for Se(0) precipitation. Here, we present the first report on the biotransformation of tellurium and selenium oxyanions into extracellular Te(0) and Se(0)nanoprecipitates (NPs) by anaerobic photosynthetically growing cultures of R. capsulatus as a function of exogenously added redox-mediator lawsone, i.e. 2-hydroxy-1,4-naphthoquinone. The NPs formation was dependent on the carbon source used for the bacterial growth and the rate of chalcogen reduction was constant at different lawsone concentrations, in line with a catalytic role for the redox mediator. X-ray diffraction (XRD) analysis demonstrated the Te(0) and Se(0) nature of the nanoparticles. PMID:24462199

  13. Conjugated polymer and drug co-encapsulated nanoparticles for Chemo- and Photo-thermal Combination Therapy with two-photon regulated fast drug release

    NASA Astrophysics Data System (ADS)

    Yuan, Youyong; Wang, Zuyong; Cai, Pingqiang; Liu, Jie; Liao, Lun-De; Hong, Minghui; Chen, Xiaodong; Thakor, Nitish; Liu, Bin

    2015-02-01

    The spatial-temporal synchronization of photothermal therapy and chemotherapy is highly desirable for an efficient cancer treatment with synergistic effect. Herein, we developed a chemotherapeutic drug doxorubicin (DOX) and photothermal conjugated polymer (CP) co-loaded nanoplatform using a near-infrared (NIR) laser responsive amphiphilic brush copolymer as the encapsulation matrix. The obtained nanoparticles (NPs) exhibit good monodispersity and excellent stability, which can efficiently convert laser energy into thermal energy for photothermal therapy. Moreover, the hydrophobic polymer matrix bearing a number of 2-diazo-1,2-naphthoquinones (DNQ) moieties could be transformed to a hydrophilic one upon NIR two-photon laser irradiation, which leads to fast drug release. Furthermore, the surface modification of the NPs with cyclic arginine-glycine-aspartic acid (cRGD) tripeptide significantly enhances the accumulation of the NPs within integrin ?v?3 overexpressed cancer cells. The half-maximal inhibitory concentration (IC50) of the combination therapy is 13.7 ?g mL-1, while the IC50 for chemotherapy and photothermal therapy alone is 147.8 ?g mL-1 and 36.2 ?g mL-1, respectively. The combination index (C.I.) is 0.48 (<1), which indicates the synergistic effect for chemotherapy and PTT. These findings provide an excellent NIR laser regulated nanoplatform for combined cancer treatment with synergistic effect due to the synchronous chemo- and photo-thermal therapy.

  14. Direct evidence that the rifamycin polyketide synthase assembles polyketide chains processively

    PubMed Central

    Yu, Tin-Wein; Shen, Yuemao; Doi-Katayama, Yukiko; Tang, Li; Park, Cheonseok; Moore, Bradley S.; Richard Hutchinson, C.; Floss, Heinz G.

    1999-01-01

    The assembly of the polyketide backbone of rifamycin B on the type I rifamycin polyketide synthase (PKS), encoded by the rifA–rifE genes, is terminated by the product of the rifF gene, an amide synthase that releases the completed undecaketide as its macrocyclic lactam. Inactivation of rifF gives a rifamycin B nonproducing mutant that still accumulates a series of linear polyketides ranging from the tetra- to a decaketide, also detected in the wild type, demonstrating that the PKS operates in a processive manner. Disruptions of the rifD module 8 and rifE module 9 and module 10 genes also result in accumulation of such linear polyketides as a consequence of premature termination of polyketide assembly. Whereas the tetraketide carries an unmodified aromatic chromophore, the penta- through decaketides have undergone oxidative cyclization to the naphthoquinone, suggesting that this modification occurs during, not after, PKS assembly. The structure of one of the accumulated compounds together with 18O experiments suggests that this oxidative cyclization produces an 8-hydroxy-7,8-dihydronaphthoquinone structure that, after the stage of proansamycin X, is dehydrogenated to an 8-hydroxynaphthoquinone. PMID:10430893

  15. Direct evidence that the rifamycin polyketide synthase assembles polyketide chains processively.

    PubMed

    Yu, T W; Shen, Y; Doi-Katayama, Y; Tang, L; Park, C; Moore, B S; Richard Hutchinson, C; Floss, H G

    1999-08-01

    The assembly of the polyketide backbone of rifamycin B on the type I rifamycin polyketide synthase (PKS), encoded by the rifA-rifE genes, is terminated by the product of the rifF gene, an amide synthase that releases the completed undecaketide as its macrocyclic lactam. Inactivation of rifF gives a rifamycin B nonproducing mutant that still accumulates a series of linear polyketides ranging from the tetra- to a decaketide, also detected in the wild type, demonstrating that the PKS operates in a processive manner. Disruptions of the rifD module 8 and rifE module 9 and module 10 genes also result in accumulation of such linear polyketides as a consequence of premature termination of polyketide assembly. Whereas the tetraketide carries an unmodified aromatic chromophore, the penta- through decaketides have undergone oxidative cyclization to the naphthoquinone, suggesting that this modification occurs during, not after, PKS assembly. The structure of one of the accumulated compounds together with (18)O experiments suggests that this oxidative cyclization produces an 8-hydroxy-7, 8-dihydronaphthoquinone structure that, after the stage of proansamycin X, is dehydrogenated to an 8-hydroxynaphthoquinone. PMID:10430893

  16. Evaluation of radical scavenging properties of shikonin

    PubMed Central

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

    2014-01-01

    With the aim of developing effective anti-inflammatory drugs, we have been investigating the biochemical effects of shikonin of “Shikon” roots, which is a naphthoquinone with anti-inflammatory and antioxidative properties. Shikonin scavenged reactive oxygen species like hydroxyl radical, superoxide anion (O2•?) and singlet oxygen in previous studies, but its reactivity with reactive oxygen species is not completely understood, and comparison with standard antioxidants is lacking. This study aimed elucidation of the reactivity of shikonin with nitric oxide radical and reactive oxygen species such as alkyl-oxy radical and O2•?. By using electron paramagnetic resonance spectrometry, shikonin was found unable of reacting with nitric oxide radical in a competition assay with oxyhemoglobin. However, shikonin scavenged alkyl-oxy radical from 2,2'-azobis(2-aminopropane) dihydrochloride with oxygen radical absorbance capacity, ORAC of 0.25 relative to Trolox, and showed a strong O2•?-scavenging ability (42-fold of Trolox; estimated reaction rate constant: 1.7 × 105 M?1s?1) in electron paramagnetic resonance assays with CYPMPO as spin trap. Concerning another source of O2•?, the phagocyte NADPH oxidase (Nox2), shikonin inhibited the Nox2 activity by impairing catalysis when added before enzyme activation (IC50: 1.1 µM; NADPH oxidation assay). However, shikonin did not affect the preactivated Nox2 activity, although having potential to scavenge produced O2•?. In conclusion, shikonin scavenged O2•? and alkyl-oxy radical, but not nitric oxide radical. PMID:25320455

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

    PubMed

    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

    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

  18. Cloning and expression of the gene encoding flavodoxin from Desulfovibrio vulgaris (Miyazaki F).

    PubMed

    Kitamura, M; Sagara, T; Taniguchi, M; Ashida, M; Ezoe, K; Kohno, K; Kojima, S; Ozawa, K; Akutsu, H; Kumagai, I; Nakaya, T

    1998-05-01

    The gene encoding a flavodoxin of Desulfovibrio vulgaris (Miyazaki F) was cloned, and overexpressed in Escherichia coli. A 1.6-kbp DNA fragment, isolated from D. vulgaris (Miyazaki F) by double digestion with SalI and EcoRI, contained the flavodoxin gene and its regulatory region. An expression system for the flavodoxin gene under control of the T7 promoter was constructed in E. coli. The purified protein was soluble and exhibited a characteristic visible absorption spectrum. HPLC analysis of the recombinant flavodoxin revealed the presence of an identical FMN to that found in the native D. vulgaris flavodoxin, and its dissociation constant with FMN was determined to be 0.38 nM. In vitro H2 reduction analysis indicated that the recombinant flavodoxin is active, and its redox potential was determined to be E1 = -434 and E2 = -151 mV using methyl viologen and 2-hydroxy-1,4-naphthoquinone, respectively. Its redox behavior was also examined with the recombinant flavodoxin adsorbed onto a graphite electrode. The mutant, A16E, was also produced, which revealed the feature of a conserved Glu residue at the surface of the molecule. PMID:9562622

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

    PubMed

    Liu, Ruijuan; Wang, Mengmeng; Ding, Li

    2014-10-01

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

  20. Biopesticides from plants: Calceolaria integrifolia s.l.

    PubMed

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

    2014-07-01

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

  1. Cytotoxic Effects of N-(3-Chloro-1,4-dioxo 1,4-dihydronaphthalen-2-yl)-benzamide on Androgen-dependent and -independent Prostate Cancer Cell Lines

    PubMed Central

    KANAAN, YASMINE M.; WHITE, DOUGLAS F.; DAS, JHARNA R.; BERHE, SOLOMON; BAKARE, OLADAPO; KENGUELE, HILLAIRE; BEYENE, DESTA; ZHOU, YANFEI; DAY, AGNES A.; COPELAND, ROBERT L.

    2013-01-01

    Background Worldwide among men, prostate cancer ranks third in cancer occurrence and sixth in cancer mortality. A number of 1, 4-naphthoquinone derivatives have been identified that possess significant pharmacological effects associated with antitumor activities. In this study, the in vitro effects of N-(3-chloro-1,4-dioxo 1,4-dihydronaphthalen-2-yl)-benzamide (NCDDNB) were evaluated on androgen-dependent (CWR-22) and androgen-independent (PC-3, DU-145) human prostate cancer cell lines, and on a normal bone marrow cell line (HS-5). Specifically, the in vitro activity of this compound on cell cycle regulation and apoptosis was evaluated. Materials and Methods Established methods of cell viability, cell cycle, Western blot and apoptosis were used. Results The effect of NCDDNB on CWR-22, PC-3, DU-145 and HS-5 cells revealed significant anti-tumor activities with IC50s, of 2.5, 2.5, 6.5, and 25 ?M respectively. The results of cell cycle analysis showed that NCDDNB arrested PC-3, DU-145, and CWR-22 cells in the G1-phase of the cell cycle. The compound showed no effect on the cell cycle progression in the HS-5 bone marrow cell line. These findings were further validated using Western blot analysis. NCDDNB showed the greatest amount of apoptosis in the androgen-independent PC-3 cells in a time-dependent manner with the apoptotic apex at day 5 of treatment. Furthermore, NCDDNB induced-apoptosis in DU-145 and CWR-22 cells peaked at day 3 of treatment. Conclusion Although the mechanism of action of this compound has not been completely elucidated, the effect on the cell cycle and the induction of apoptosis in different prostate cancer cell lines prompted us to carry out a more in-depth preclinical evaluation. This study suggests that NCDDNB may have an impact on treatment of prostate cancer while protecting the bone marrow. PMID:20332464

  2. Potential of herbs in skin protection from ultraviolet radiation

    PubMed Central

    Kora?, Radava R.; Khambholja, Kapil M.

    2011-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  4. Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol

    SciTech Connect

    Maeda, Masayo [Department of Chemistry, Kanazawa Medical University, Uchinada, Ishikawa 920-0293 (Japan); Murakami, Manabu; Takegami, Tsutomu [Division of Molecular Oncology and Virology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293 (Japan); Ota, Takahide [Division of Molecular Oncology and Virology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293 (Japan)], E-mail: takahide@kanazawa-med.ac.jp

    2008-06-01

    Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent.

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

    NASA Astrophysics Data System (ADS)

    Koike, Eiko; Yanagisawa, Rie; Takano, Hirohisa

    2014-11-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  8. Potential of herbs in skin protection from ultraviolet radiation.

    PubMed

    Kora?, Radava R; Khambholja, Kapil M

    2011-07-01

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

  9. Subtle changes in endochin-like quinolone structure alter the site of inhibition within the cytochrome bc1 complex of Plasmodium falciparum.

    PubMed

    Stickles, Allison M; de Almeida, Mariana Justino; Morrisey, Joanne M; Sheridan, Kayla A; Forquer, Isaac P; Nilsen, Aaron; Winter, Rolf W; Burrows, Jeremy N; Fidock, David A; Vaidya, Akhil B; Riscoe, Michael K

    2015-04-01

    The cytochrome bc1 complex (cyt bc1) is the third component of the mitochondrial electron transport chain and is the target of several potent antimalarial compounds, including the naphthoquinone atovaquone (ATV) and the 4(1H)-quinolone ELQ-300. Mechanistically, cyt bc1 facilitates the transfer of electrons from ubiquinol to cytochrome c and contains both oxidative (Qo) and reductive (Qi) catalytic sites that are amenable to small-molecule inhibition. Although many antimalarial compounds, including ATV, effectively target the Qo site, it has been challenging to design selective Qi site inhibitors with the ability to circumvent clinical ATV resistance, and little is known about how chemical structure contributes to site selectivity within cyt bc1. Here, we used the proposed Qi site inhibitor ELQ-300 to generate a drug-resistant Plasmodium falciparum clone containing an I22L mutation at the Qi region of cyt b. Using this D1 clone and the Y268S Qo mutant strain, P. falciparum Tm90-C2B, we created a structure-activity map of Qi versus Qo site selectivity for a series of endochin-like 4(1H)-quinolones (ELQs). We found that Qi site inhibition was associated with compounds containing 6-position halogens or aryl 3-position side chains, while Qo site inhibition was favored by 5,7-dihalogen groups or 7-position substituents. In addition to identifying ELQ-300 as a preferential Qi site inhibitor, our data suggest that the 4(1H)-quinolone scaffold is compatible with binding to either site of cyt bc1 and that minor chemical changes can influence Qo or Qi site inhibition by the ELQs. PMID:25605352

  10. Monoamine Oxidase Inhibitors Extracted from Tobacco Smoke as Neuroprotective Factors for Potential Treatment of Parkinson's Disease.

    PubMed

    Sari, Youssef; Khalil, Ashraf

    2015-01-01

    Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of mainly the nigrostriatal dopaminergic neurons, which leads to motor dysfunction. Although, most of the drugs are currently used for symptomatic treatment, there are at least three FDA-approved drugs for the treatment of PD that have been suggested preclinically to have neuroprotective effects. Among these drugs are monoamine oxidase (MAO) type B inhibitors such as selegiline and rasagiline, and non-ergot derivative dopamine agonist, pramipexole. In this review article, we focused on the potential uses of non-selective reversible MAO inhibitor, 2,3,6-trimethyl-1,4-naphthoquinone, from flue-cured tobacco leaves extract and two ?- carboline alkaloids (harman and norharman) as potent, reversible and non-selective MAO inhibitors for the treatment of PD. In addition, we discussed the potential uses of farnesol as a potent inhibitor of MAO-B and farnesylacetone as a less potent selective MAO-B inhibitor. Furthermore, adducts of 1,2,3,4-tetrahydroisoquinoline have shown to have competitive inhibitory effects for both MAO-A and MAO-B. These inhibitors have potential neuroprotective effects, which might be mediated at least through nerve growth factor, neurotrophin 3, brain derived neurotrophic factor, and glial-cell-line-derived neurotrophic factor. We suggest here the neuroprotective implication of extracted MAO inhibitors from smoke tobacco; however, it is important to note that there are several existing compounds in tobacco smoke that have toxic effects in the brain, these include and not limited to the induction of neuropathological features observed in individuals suffering from Alzheimer's disease and dementia. PMID:25808895

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

    PubMed

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

    2014-04-22

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

  12. Redox modulation of global phosphatase activity and protein phosphorylation in intact skeletal muscle.

    PubMed

    Wright, Valerie P; Reiser, Peter J; Clanton, Thomas L

    2009-12-01

    Skeletal muscles produce transient reactive oxygen species (ROS) in response to intense stimulation, disuse atrophy, heat stress, hypoxia, osmotic stress, stretch and cell receptor activation. The physiological significance is not well understood. Protein phosphatases (PPases) are known to be highly sensitive to oxidants and could contribute to many different signalling responses in muscle. We tested whether broad categories of PPases are inhibited by levels of acute oxidant exposure that do not result in loss of contractile function or gross oxidative stress. We also tested if this exposure results in elevated levels of global protein phosphorylation. Rat diaphragm muscles were treated with either 2,3-dimethoxy-1-naphthoquinone (DMNQ; 1, 10, 100 microm; a mitochondrial O(2)(.-)/H2O2 generator) or exogenous H2O2 (5, 50, 500 microm) for 30 min. Supernatants were assayed for serine/threonine PPase (Ser/Thr-PPase) or protein tyrosine PPase (PTP) activities. With the exception of 500 microm H2O2, no other oxidant exposures significantly elevated protein carbonyl formation, nor did they alter the magnitude of twitch force. DMNQ significantly decreased all categories of PPase activity at 10 and 100 microm and reduced PTP at 1 microm. Similar reductions in Ser/Thr-PPase activity were seen in response to 50 and 500 microm H2O2 and PTP at 500 microm H2O2. ROS treatments resulted a dose-dependent increase in the phosphorylation states of many proteins. The data are consistent with the concept that PPases, within intact skeletal muscles, are highly sensitive to acute changes in ROS activity and that localized ROS play a critical role in lowering the barriers for effective phosphorylation events to occur in muscle cells, thus increasing the probability for cell signalling responses to proceed. PMID:19841000

  13. Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice.

    PubMed

    Müller, Joachim; Aguado-Martinez, Adriana; Manser, Vera; Balmer, Vreni; Winzer, Pablo; Ritler, Dominic; Hostettler, Isabel; Arranz-Solís, David; Ortega-Mora, Luis; Hemphill, Andrew

    2015-04-01

    The naphthoquinone buparvaquone is currently the only drug used against theileriosis. Here, the effects of buparvaquone were investigated in vitro and in an experimental mouse model for Neospora caninum infection. In 4-day proliferation assays, buparvaquone efficiently inhibited N.?caninum tachyzoite replication (IC50?=?4.9?nM; IC100?=?100?nM). However, in the long term tachyzoites adapted and resumed proliferation in the presence of 100?nM buparvaquone after 20 days of cultivation. Parasiticidal activity was noted after 9 days of culture in 0.5?µM or 6 days in 1?µM buparvaquone. TEM of N.?caninum infected fibroblasts treated with 1?µM buparvaquone showed that the drug acted rather slowly, and ultrastructural changes were evident only after 3-5 days of treatment, including severe alterations in the parasite cytoplasm, changes in the composition of the parasitophorous vacuole matrix and a diminished integrity of the vacuole membrane. Treatment of N.?caninum infected mice with buparvaquone (100?mg/kg) either by intraperitoneal injection or gavage prevented neosporosis symptoms in 4 out of 6 mice in the intraperitoneally treated group, and in 6 out of 7 mice in the group receiving oral treatment. In the corresponding controls, all 6 mice injected intraperitoneally with corn oil alone died of acute neosporosis, and 4 out of 6 mice died in the orally treated control group. Assessment of infection intensities in the treatment groups showed that, compared to the drug treated groups, the controls showed a significantly higher parasite load in the lungs while cerebral parasite load was higher in the buparvaquone-treated groups. Thus, although buparvaquone did not eliminate the parasites infecting the CNS, the drug represents an interesting lead with the potential to eliminate, or at least diminish, fetal infection during pregnancy. PMID:25941626

  14. 2-Methoxystypandrone ameliorates brain function through preserving BBB integrity and promoting neurogenesis in mice with acute ischemic stroke.

    PubMed

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

    2014-02-01

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

  15. Screening of inbred lines to develop a thermotolerant sunflower hybrid using the temperature induction response (TIR) technique: a novel approach by exploiting residual variability.

    PubMed

    Senthil-Kumar, M; Srikanthbabu, V; Mohan Raju, B; Ganeshkumar; Shivaprakash, N; Udayakumar, M

    2003-11-01

    Plants, when exposed to sub-lethal stress (induction stress), develop the ability to withstand severe temperatures and this phenomenon is often referred to as acquired thermotolerance. Earlier it was reported that induction stress alters gene expression and brings greater adaptation to heat stress and that the genetic variability in thermotolerance is only seen upon induction stress. Based on this concept, the temperature induction response (TIR) technique has been developed to identify thermotolerant lines. By following the TIR technique, sunflower hybrid KBSH-1 parents were screened for high temperature tolerance. Seedlings of parental lines including CMS 234 A, CMS 234 B and 6 D-1 showed considerable genetic variability for thermotolerance and it was attributed to the expression of existing residual variability for stress responses. Thus, the existing variability forms the basis for identifying thermotolerant lines. The identified parental inbred lines were selected and established in the field and crossed to get F1 hybrid seeds. The KBSH-1 hybrid developed from selected variants of parental lines was compared with the original KBSH-1 for thermotolerance. The selected KBSH-1 was more tolerant compared with the original hybrid both at the seedling as well as at the plant level. The physiological and molecular basis of thermotolerance was studied in the KBSH-1 original and the hybrid developed from selected variants of parental lines. The selected hybrid exhibited high tolerance to Menadione (naphthoquinone)-induced oxidative stress. Even the methyl viologen-induced oxidative stress damage was relatively less in the selected hybrid population. The selected hybrid also showed enhanced expression of the heat shock proteins HSP 90 and HSP 104 and also accumulated higher levels of the heat shock transcription factor HSFA. PMID:14565951

  16. YY1 positively regulates human UBIAD1 expression.

    PubMed

    Funahashi, Nobuaki; Hirota, Yoshihisa; Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato; Suhara, Yoshitomo; Okano, Toshio

    2015-05-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K1) and a series of bacterial menaquionones (MK-n; vitamin K2). Menadione (vitamin K3) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5' rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. PMID:25772619

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

    PubMed

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

    2007-06-01

    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

  18. Accelerated removal of Sudan dye by Shewanella oneidensis MR-1 in the presence of quinones and humic acids.

    PubMed

    Liu, Guangfei; Zhou, Jiti; Ji, Qiuyan; Wang, Jing; Jin, Ruofei; Lv, Hong

    2013-09-01

    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

  19. Stability of flavin semiquinones in the gas phase: the electron affinity, proton affinity, and hydrogen atom affinity of lumiflavin.

    PubMed

    Zhang, Tianlan; Papson, Kaitlin; Ochran, Richard; Ridge, Douglas P

    2013-11-01

    Examination of electron transfer and proton transfer reactions of lumiflavin and proton transfer reactions of the lumiflavin radical anion by Fourier transform ion cyclotron resonance mass spectrometry is described. From the equilibrium constant determined for electron transfer between 1,4-naphthoquinone and lumiflavin the electron affinity of lumiflavin is deduced to be 1.86 ± 0.1 eV. Measurements of the rate constants and efficiencies for proton transfer reactions indicate that the proton affinity of the lumiflavin radical anion is between that of difluoroacetate (331.0 kcal/mol) and p-formyl-phenoxide (333.0 kcal/mol). Combining the electron affinity of lumiflavin with the proton affinity of the lumiflavin radical anion gives a lumiflavin hydrogen atom affinity of 59.7 ± 2.2 kcal/mol. The ?G298 deduced from these results for adding an H atom to gas phase lumiflavin, 52.1 ± 2.2 kcal/mol, is in good agreement with ?G298 for adding an H atom to aqueous lumiflavin from electrochemical measurements in the literature, 51.0 kcal/mol, and that from M06-L density functional calculations in the literature, 51.2 kcal/mol, suggesting little, if any, solvent effect on the H atom addition. The proton affinity of lumiflavin deduced from the equilibrium constant for the proton transfer reaction between lumiflavin and 2-picoline is 227.3 ± 2.0 kcal mol(-1). Density functional theory calculations on isomers of protonated lumiflavin provide a basis for assigning the most probable site of protonation as position 1 on the isoalloxazine ring and for estimating the ionization potentials of lumiflavin neutral radicals. PMID:24007273

  20. Antiparasitic activities of novel ruthenium/lapachol complexes.

    PubMed

    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

    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

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

    PubMed Central

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

    2014-01-01

    Background: Cnidoscolus quercifolius is a species popularly known as favela and faveleira, and belonging to the Caatinga biome (semi-arid vegetation, Brazil), where is used in folk medicine as an anti-inflammatory. Objective: The aim was to evaluate the anti-inflammatory effect of the ethanolic extract from barks (Cqb-EtOH) and leaves (Cql-EtOH) of C. quercifolius in mice using experimental models of inflammation. Materials and Methods: The preliminary phytochemical analysis of the ethanolic extract was performed. The activity was evaluated by paw edema induced by carrageenan and leukocytes migration to the peritoneal cavity induced by carrageenan methods. Results: A preliminary analysis of Cqb-EtOH revealed that it contained coumarins, flavonoids, monoterpenes/diterpenes and naphthoquinones, while the Cql-EtOH showed positive reaction to coumarins, anthracene derivatives, flavonoids, lignans and triterpenes/steroids. Cqb-EtOH and Cql-EtOH (100, 200 and 400 mg/kg) inhibited significantly (P < 0.01) the increase in the edema volume after administration of carrageenan. In the peritonitis test, acute pretreatment with Cqb-EtOH and Cql-EtOH (100, 200 and 400 mg/kg) inhibited the leukocyte migration. Conclusions: It can be concluded that extracts from the barks and leaves of C. quercifolius have anti-inflammatory activity, which supports the popular use of this plant to treat inflammation. Thus, extracts has significant anti-inflammatory properties, which are related probably to inhibition of release of mediators of the inflammatory process. PMID:25276074

  2. Analysis of Naphthalene Adduct Binding Sites in Model Proteins by Tandem Mass Spectrometry

    PubMed Central

    Pham, Nathalie T.; Jewell, William T.; Morin, Dexter; Buckpitt, Alan R.

    2013-01-01

    The electrophilic metabolites of the polyaromatic hydrocarbon naphthalene have been shown to bind covalently to proteins and covalent adduct formation correlates with the cytotoxic effects of the chemical in the respiratory system. Although 1,2-naphthalene epoxide, naphthalene diol epoxide, 1,2-naphthoquinone, and 1,4-napthoquinone have been identified as reactive metabolites of interest, the role of each metabolite in total covalent protein adduction and subsequent cytotoxicity remains to be established. To better understand the target residues associated with the reaction of these metabolites with proteins, mass spectrometry was used to identify adducted residues following 1) incubation of metabolites with actin and protein disulfide isomerase (PDI), and 2) activation of naphthalene in microsomal incubations containing supplemental actin or PDI. All four reactive metabolites bound to Cys, Lys or His residues in actin and PDI. Cys17 of actin was the only residue adducted by all metabolites; there was substantial metabolite selectivity for the majority of adducted residues. Modifications of actin and PDI, following microsomal incubations containing 14C-naphthalene, were detected readily by 2D gel electrophoresis and phosphor imaging. However, target modifications on tryptic peptides from these isolated proteins could not be readily detected by MALDI/TOF/TOF and only three modified peptides were detected using high resolution – selective ion monitoring (HR-SIM). All the reactive metabolites investigated have the potential to modify several residues in a single protein, but even in tissues with very high rates of naphthalene activation, the extent of modification was too low to allow unambiguous identification of a significant number of modified residues in the isolated proteins. PMID:22659010

  3. Enhancement of DMNQ-induced hepatocyte toxicity by cytochrome P450 inhibition

    SciTech Connect

    Ishihara, Yasuhiro [Department of Biology, Graduate School of Science, Osaka University, Osaka 532-8686 (Japan); Shiba, Dai [Department of Biology, Graduate School of Science, Osaka University, Osaka 532-8686 (Japan); Shimamoto, Norio [Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1, Shido, Sanuki, Kagawa 769-2193 (Japan)]. E-mail: n-shimamoto@kph.bunri-u.ac.jp

    2006-07-15

    Two mechanisms have been proposed to explain quinone cytotoxicity: oxidative stress via the redox cycle and the arylation of intracellular nucleophiles. As the redox cycle is catalyzed by NADPH cytochrome P450 reductase, cytochrome P450 systems are expected to be related to the cytotoxicity induced by redox-cycling quinones. Thus, we investigated the relationship between cytochrome P450 systems and quinone toxicity for rat primary hepatocytes using an arylator, 1,4-benzoquinone (BQ), and a redox cycler, 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). The hepatocyte toxicity of both BQ and DMNQ increased in a time- and dose-dependent manner. Pretreatment with cytochrome P450 inhibitors, such as SKF-525A (SKF), ketoconazole and 2-methy-1,2-di-3-pyridyl-1-propanone, enhanced the hepatocyte toxicity induced by DMNQ but did not affect BQ-induced hepatocyte toxicity. The production of superoxide anion and the levels of glutathione disulfide and thiobarbituric-acid-reactive substances were increased by treatment with DMNQ, and SKF pretreatment further enhanced their increases. In addition, NADPH oxidation in microsomes was increased by treatment with DMNQ and further augmented by pretreatment with SKF, and a NADPH cytochrome P450 reductase inhibitor, diphenyleneiodonium chloride completely suppressed NADPH oxidations increased by treatment with either DMNQ- or DMNQ + SKF. Pretreatment with antioxidants, such as {alpha}-tocopherol, reduced glutathione, N-acetyl cysteine or an iron ion chelator deferoxamine, totally suppressed DMNQ- and DMNQ + SKF-induced hepatocyte toxicity. These results indicate that the hepatocyte toxicity of redox-cycling quinones is enhanced under cytochrome P450 inhibition, and that this enhancement is caused by the potentiation of oxidative stress.

  4. Sequence organization and regulation of the Bacillus subtilis menBE operon.

    PubMed Central

    Driscoll, J R; Taber, H W

    1992-01-01

    Menaquinone (MK) plays a central role in the respiratory chain of Bacillus subtilis. The biosynthesis of MK requires the formation of a naphthoquinone ring via a series of specific reactions branching from the shikimate pathway. "Early" MK-specific reactions catalyze the formation of o-succinylbenzoate (OSB) from isochorismate, and "late" reactions convert OSB to dihydroxynaphthoate, by utilizing an OSB-coenzyme A intermediate. We have cloned and sequenced the B. subtilis menE and menB genes encoding, respectively, OSB-coenzyme A synthase and dihydroxynaphthoate synthase. The MenB open reading frame encodes a potential polypeptide of 261 amino acid residues with a predicted size of 28.5 kDa, while the MenE open reading frame could encode a 24.4-kDa polypeptide of 220 amino acid residues. Probable promoter sequences were identified by high-resolution primer extension assays. Organization of these genes and regulatory regions was found to be menBp menB menEp menE. Expression of menE was dependent on both menEp and menBp, indicating an operonlike organization. A region of dyad symmetry capable of forming a stable RNA secondary structure was found between menB and menE. Culture cycle-dependent expression of menB and menE was measured by steady-state transcript accumulation. For both genes, maximal accumulation was found to occur within an hour after the end of exponential growth. The menBp and menEp promoters have sequences compatible with recognition by the major vegetative form of B. subtilis RNA polymerase, E sigma A. Both promoter regions also were found to contain homologies to a sequence motif previously identified in the menCDp region and in promoters for several B. subtilis tricarboxylic acid cycle genes. Images PMID:1629163

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

    PubMed Central

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

    2012-01-01

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

  6. An efficient one-pot reaction for selective fluorimetric determination of cefpodoxime and its prodrug.

    PubMed

    Mohamed, Niveen A; Abdel-Wadood, Hanaa M; Ahmed, Sameh

    2011-09-30

    Cefpodoxime proxetil (CFP), an oral third-generation cephalosporin, is a prodrug that is de-esterified in vivo to its active metabolite, cefpodoxime acid (CFA). Therefore, this study aimed to develop a facile and efficient one-pot reaction for selective and sensitive determination of CFA and its prodrug (CFP). The method was based on single-step reaction between CFP or CFA and 1,2-naphthoquinone-4-sulfonate (NQS) as a selective derivatizing reagent in alkaline medium without heating, extraction or reduction steps as usual for NQS derivatization reactions. The fluorescence of the formed NQS-derivative was monitored directly at emission wavelength of 440 nm after excitation at 330 nm. The method can easily be implemented in plating facilities by operators and/or incorporated in on-line derivatization reaction. The correlation coefficients of 0.9991 and 0.9984 were obtained in the concentration ranges of 50-2000 ng mL(-1) for CFA and CFP, respectively. The detection limits were 9.17 and 9.48 ng mL(-1) for CFA and CFP, respectively. The method was validated in accordance with the requirements of ICH guidelines and shown to be suitable for their efficient and sensitive determinations. The developed method was successfully applied for selective determination of CFP in pure form and in pharmaceutical dosage forms as well as CFA in human urine after single dose of CFP without prior need for separation. The method is valuable for quality control laboratories for monitoring of CFP and its active metabolite CFA. PMID:21872067

  7. The Mycobacterium tuberculosis Rv2540c DNA sequence encodes a bifunctional chorismate synthase

    PubMed Central

    Ely, Fernanda; Nunes, José ES; Schroeder, Evelyn K; Frazzon, Jeverson; Palma, Mário S; Santos, Diógenes S; Basso, Luiz A

    2008-01-01

    Background The emergence of multi- and extensively-drug resistant Mycobacterium tuberculosis strains has created an urgent need for new agents to treat tuberculosis (TB). The enzymes of shikimate pathway are attractive targets to the development of antitubercular agents because it is essential for M. tuberculosis and is absent from humans. Chorismate synthase (CS) is the seventh enzyme of this route and catalyzes the NADH- and FMN-dependent synthesis of chorismate, a precursor of aromatic amino acids, naphthoquinones, menaquinones, and mycobactins. Although the M. tuberculosis Rv2540c (aroF) sequence has been annotated to encode a chorismate synthase, there has been no report on its correct assignment and functional characterization of its protein product. Results In the present work, we describe DNA amplification of aroF-encoded CS from M. tuberculosis (MtCS), molecular cloning, protein expression, and purification to homogeneity. N-terminal amino acid sequencing, mass spectrometry and gel filtration chromatography were employed to determine identity, subunit molecular weight and oligomeric state in solution of homogeneous recombinant MtCS. The bifunctionality of MtCS was determined by measurements of both chorismate synthase and NADH:FMN oxidoreductase activities. The flavin reductase activity was characterized, showing the existence of a complex between FMNox and MtCS. FMNox and NADH equilibrium binding was measured. Primary deuterium, solvent and multiple kinetic isotope effects are described and suggest distinct steps for hydride and proton transfers, with the former being more rate-limiting. Conclusion This is the first report showing that a bacterial CS is bifunctional. Primary deuterium kinetic isotope effects show that C4-proS hydrogen is being transferred during the reduction of FMNox by NADH and that hydride transfer contributes significantly to the rate-limiting step of FMN reduction reaction. Solvent kinetic isotope effects and proton inventory results indicate that proton transfer from solvent partially limits the rate of FMN reduction and that a single proton transfer gives rise to the observed solvent isotope effect. Multiple isotope effects suggest a stepwise mechanism for the reduction of FMNox. The results on enzyme kinetics described here provide evidence for the mode of action of MtCS and should thus pave the way for the rational design of antitubercular agents. PMID:18445278

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

    PubMed Central

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

    2014-01-01

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

  9. Direct quantitative determination of cyanamide by stable isotope dilution gas chromatography-mass spectrometry.

    PubMed

    Hiradate, Syuntaro; Kamo, Tsunashi; Nakajima, Eri; Kato, Kenji; Fujii, Yoshiharu

    2005-12-01

    Cyanamide is a multifunctional agrochemical used, for example, as a pesticide, herbicide, and fertilizer. Recent research has revealed that cyanamide is a natural product biosynthesized in a leguminous plant, hairy vetch (Vicia villosa). In the present study, gas chromatography-mass spectrometry (GC-MS) equipped with a capillary column for amines was used for direct quantitative determination of cyanamide. Quantitative signals for ((14)N(2))cyanamide, ((15)N(2))cyanamide (internal standard for stable isotope dilution method), and m-(trifluoromethyl)benzonitrile (internal standard for correcting errors in GC-MS analysis) were recorded as peak areas on mass chromatograms at m/z 42 (A(42)), 44 (A(44)), and 171 (A(IS)), respectively. Total cyanamide content, ((14)N(2))cyanamide plus ((15)N(2))cyanamide, was determined as a function of (A(42)+A(44))/A(IS). Contents of ((14)N(2))cyanamide and ((15)N(2))cyanamide were then calculated by multiplying the total cyanamide content by A(42)/(A(42)+A(44)) and A(44)/(A(42)+A(44)), respectively. The limit of detection for the total cyanamide content by the GC-MS analysis was around 1ng. The molar ratio of ((14)N(2))cyanamide to ((15)N(2))cyanamide in the injected sample was equal to the observed A(42)/A(44) value in the range from 0.1 to 5. It was, therefore, possible to use the stable isotope dilution method to quantify the natural cyanamide content in samples; i.e., the natural cyanamide content was derived by subtracting the A(42)/A(44) ratio of the internal standard from the A(42)/A(44) ratio of sample spiked with internal standard, and then multiplying the resulting difference by the amount of added ((15)N(2))cyanamide (SID-GC-MS method). This method successfully gave a reasonable value for the natural cyanamide content in hairy vetch, concurring with the value obtained by a conventional method in which cyanamide was derivatized to a photometrically active compound 4-cyanimido-1,2-naphthoquinone and analyzed with reversed-phase HPLC (CNQ-HPLC method). The determination range of cyanamide in the SID-GC-MS method was almost the same as that in the CNQ-HPLC method; however, the SID-GC-MS method was much simpler than the CNQ-HPLC method. PMID:16314170

  10. Interaction of ascorbate with photosystem I.

    PubMed

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

    2014-11-01

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

  11. Bioactive compounds from northern plants.

    PubMed

    Hohtola, Anja

    2010-01-01

    Northern conditions are characterised by long days with much light and low temperatures during the growing season. It has been chimed that herbs and berries grown in the north are stronger tasting compared to those of southern origin. The compounds imparting aroma and color to berries and herbs are secondary metabolites which in plants mostly act as chemical means of defense. Recently, the production of secondary metabolites using plant cells has been the subject of expanding research. Light intensity, photoperiod and temperature have been reported to influence the biosynthesis of many secondary metabolites. Native wild aromatic and medicinal plant species of different families are being studied to meet the needs of raw material for the expanding industry of e.g., health-promoting food products known as nutraceutics. There are already a large number of known secondary compounds produced by plants, but the recent advances in modern extraction and analysis should enable many more as yet unknown compounds to be found, characterised and utilised. Rose root (Rhodiola rosea) is a perennial herbaceous plant which inhabits mountain regions throughout Europe, Asia and east coastal regions of North America. The extract made from the rhizomes acts as a stimulant like the Ginseng root. Roseroot has been categorized as an adaptogen and is reported to have many pharmacological properties. The biologically active components of the extract are salitroside tyrosol and cinnamic acid glycosides (rosavin, rosarin, rosin). Round-leaved sundew (Drosera rotundifolia L.) has circumboreal distribution. It inhabits nutrient-poor, moist and sunny areas such as peat bogs and wetlands. Sundew leaves are collected from the wild-type for various medicinal preparations and can be utilized in treating e.g., as an important "cough-medicine" for different respiratory diseases. The antimicrobial activity of extracts of aerial parts against various bacteria has been investigated. Drosera produces various secondary metabolites. The most abundant, among these compounds, are the naphthoquinones. Bilberry (Vaccinium myrtillus) is a characteristic field layer species in boreal forests. Bilberry and other northern Vaccinium species, berries and leaves, contain high amounts of phenolic compounds. Bilberries are known for its exceptionally high amounts ofanthocyanins with powerful antioxidant capacity. They have been shown to possess beneficial health effects, like having a protective role in cardiovascular diseases and cancer. Many flavonoids also seem to have antiviral, antibacterial, antifungal and antiallergenic properties. The effect of ingested cranberry (V. oxycoccus) juice has been shown to prevent urinary tract infections in women. PMID:21520706

  12. Reactive Oxygen Species Production Mediated by Humic-like Substances in Atmospheric Aerosols: Enhancement Effects by Pyridine, Imidazole, and Their Derivatives.

    PubMed

    Dou, Jing; Lin, Peng; Kuang, Bin-Yu; Yu, Jian Zhen

    2015-06-01

    Ambient particulate matter (PM) can cause adverse health effects via their ability to produce reactive oxygen species (ROS). Humic-like substances (HULIS), a complex mixture of amphiphilic organic compounds, have been demonstrated to contain the majority of redox activity in the water-extractable organic fraction of PM. Reduced organic nitrogen compounds, such as alkaloids resulting from biomass burning emissions, are among HULIS constituents. In this study, we examined the redox activities of pyridine, imidazole and their alkyl derivatives using a cell-free dithiothreitol (DTT) assay under simulated physiological conditions (37 °C, pH = 7.40). These compounds were found to have little redox activity on their own as measured by the DTT assay, but they enhanced ROS generation catalyzed by 1,4-naphthoquinone (as a model quinone compound) and HULIS isolated from multiple aerosol samples. The enhancement effect by the individual nitrogen-containing bases was determined to be proportional to their amount in the assay solutions. It is postulated that the underlying mechanism involves the unprotonated N atom acting as a H-bonding acceptor to facilitate hydrogen-atom transfer in the ROS generation cycle. The enhancement capability was found to increase with their basicity (i.e., pKa of their conjugated acids, BH(+)), consistent with the proposed mechanism for enhancement. Among the imidazole homologues, a linear relationship was observed between the enhancement factors (in log scale) of the unprotonated form of the imidazole compounds (B) and the pKa of their conjugated acids (BH(+)). This relationship predicts that the range of alkylimidazole homologues (C6-C13) observed in atmospheric HULIS would be 1.5-4.4 times more effective than imidazole in facilitating HULIS-mediated ROS generation. Our work reveals that the ability of atmospheric PM organics to catalyze generation of ROS in cells could be affected by coexisting redox inactive organic constituents and suggests further work deploying multiple assays be conducted to quantify redox capabilities and enhancement effects of the HULIS components. PMID:25961507

  13. United States Department of Agriculture-Agricultural Research Service studies on polyketide toxins of Fusarium oxysporum f sp vasinfectum: potential targets for disease control.

    PubMed

    Bell, Alois A; Wheeler, Michael H; Liu, Jinggao; Stipanovic, Robert D; Puckhaber, Lorraine S; Orta, Heather

    2003-01-01

    A group of 133 isolates of the cotton wilt pathogen Fusarium oxysporum Schlecht f sp vasinfectum (Atk) Sny & Hans, representing five races and 20 vegetative compatibility groups within race 1 were used to determine the identity, biosynthetic regulation and taxonomic distribution of polyketide toxins produced by this pathogen. All isolates of F oxysporum f sp vasinfectum produced and secreted the nonaketide naphthazarin quinones, bikaverin and norbikaverin. Most isolates of race 1 (previously denoted as races 1, 2 and 6; and also called race A) also synthesized the heptaketide naphthoquinones, nectriafurone, anhydrofusarubin lactol and 5-O-methyljavanicin. Nine avirulent isolates of F oxysporum from Upland cotton roots, three isolates of race 3 of F oxysporum f sp vasinfectum, and four isolates of F oxysporum f sp vasinfectum from Australia, all of which previously failed to cause disease of Upland cotton (Gossypium hirsutum L) in stem-puncture assays, also failed to synthesize or secrete more than trace amounts of the heptaketide compounds. These results indicate that the heptaketides may have a unique role in the virulence of race 1 to Upland cotton. The synthesis of all polyketide toxins by ATCC isolate 24908 of F oxysporum f sp vasinfectum was regulated by pH, carbon/nitrogen ratios, and availability of calcium in media. Synthesis was greatest below pH 7.0 and increased progressively as carbon/nitrogen ratios were increased by decreasing the amounts of nitrogen added to media. The nonaketides were the major polyketides accumulated in synthetic media at pH 4.5 and below, whereas the heptaketides were predominant at pH 5.0 and above. The heptaketides were the major polyketides formed when 10 F oxysporum f sp vasinfectum race 1 isolates were grown on sterilized stems of Fusarium wilt-susceptible cotton cultivars, but these compounds were not produced on sorghum grain cultures. Both groups of polyketide toxins were apparently secreted by F oxysporum f sp vasinfectum, since half of the toxin in 2-day-old shake culture was present in the supernatant. Secretion was enhanced by calcium. Glutamine and glutamic acid inhibited both nonaketide and heptaketide syntheses, even at low nitrogen PMID:12846324

  14. Structural-Functional Characterization and Physiological Significance of Ferredoxin-NADP+ Reductase from Xanthomonas axonopodis pv. citri

    PubMed Central

    Delprato, María Laura; Ceccarelli, Eduardo A.; Orellano, Elena G.

    2011-01-01

    Xanthomonas axonopodis pv. citri is a phytopathogen bacterium that causes severe citrus canker disease. Similar to other phytopathogens, after infection by this bacterium, plants trigger a defense mechanism that produces reactive oxygen species. Ferredoxin-NADP+ reductases (FNRs) are redox flavoenzymes that participate in several metabolic functions, including the response to reactive oxygen species. Xanthomonas axonopodis pv. citri has a gene (fpr) that encodes for a FNR (Xac-FNR) that belongs to the subclass I bacterial FNRs. The aim of this work was to search for the physiological role of this enzyme and to characterize its structural and functional properties. The functionality of Xac-FNR was tested by cross-complementation of a FNR knockout Escherichia coli strain, which exhibit high susceptibility to agents that produce an abnormal accumulation of •O2-. Xac-FNR was able to substitute for the FNR in E. coli in its antioxidant role. The expression of fpr in X. axonopodis pv. citri was assessed using semiquantitative RT-PCR and Western blot analysis. A 2.2-fold induction was observed in the presence of the superoxide-generating agents methyl viologen and 2,3-dimethoxy-1,4-naphthoquinone. Structural and functional studies showed that Xac-FNR displayed different functional features from other subclass I bacterial FNRs. Our analyses suggest that these differences may be due to the unusual carboxy-terminal region. We propose a further classification of subclass I bacterial FNRs, which is useful to determine the nature of their ferredoxin redox partners. Using sequence analysis, we identified a ferredoxin (XAC1762) as a potential substrate of Xac-FNR. The purified ferredoxin protein displayed the typical broad UV-visible spectrum of [4Fe-4S] clusters and was able to function as substrate of Xac-FNR in the cytochrome c reductase activity. Our results suggest that Xac-FNR is involved in the oxidative stress response of Xanthomonas axonopodis pv. citri and performs its biological function most likely through the interaction with ferredoxin XAC1762. PMID:22096528

  15. Absorption of lawsone through human skin.

    PubMed

    Kraeling, Margaret E K; Bronaugh, Robert L; Jung, Connie T

    2007-01-01

    Lawsone (2-hydroxy-1,4-naphthoquinone) is the principal color ingredient in henna, a color additive approved with limitations for coloring hair by the Food and Drug Administration (FDA) under 21 CFR 73.2190. In 2002, the scientific committee on cosmetics and non-food products (SCCNFP), now known as the scientific committee for consumer products (SCCP), evaluated the safety of lawsone as a coloring agent in hair dye products of the European Union (EU). The SCCNFP concluded that lawsone was mutagenic and not suitable for use as a hair coloring agent. As a result, studies were conducted to measure the extent of lawsone absorption through human skin. Lawsone skin absorption was determined from two hair coloring products and two shampoo products, all containing henna. [(14)C]-Lawsone (sp. act. 22.9 mCi/mmol) was added to each commercial product and the products were applied to dermatomed, nonviable human skin mounted in flow-through diffusion cells perfused with a physiological buffer (HEPES-buffered Hanks' balanced salt solution, pH 7.4). Products remained on the skin for 5 minutes (shampoos) and 1 hour (hair color paste). For the henna hair paste products, 0.3 and 1.3% of the applied dose was absorbed into the receptor fluid in 24 hours while 2.2 and 4.0% remained in the skin. For both henna shampoo products, 0.3% of the applied dose was absorbed into the receptor fluid at 24 hours while 3.6 and 6.8% remained in the skin. For all products, most of the lawsone applied was washed from the surface of the skin (83-102%) at the end of the exposure period. Extended absorption studies were conducted for 72 hours to determine if skin levels of lawsone in the 24 hour studies might eventually be percutaneously absorbed. These studies determined that the majority of the lawsone remained in the skin with only a small but significant increase (for three out of four products) in receptor fluid values. Therefore, it appears that receptor fluid values would give a good estimate of lawsone absorption for an exposure estimate and that skin levels of lawsone need not be included. PMID:17464748

  16. Transformation of carbon tetrachloride by thiol reductants in the presence of quinone compounds.

    PubMed

    Doong, Ruey-An; Chiang, Huai-Chih

    2005-10-01

    Quinones are present in trace amounts in natural organic matter. The addition of thiol compounds to quinones produces reactive electron-transfer species that may be important for the transformation of chlorinated hydrocarbons under sulfate-reducing conditions. This study systematically investigated the transformation of carbon tetrachloride (CCl4) in homogeneous aqueous solutions containing quinones as electron-transfer mediators and thiol compounds as bulk reductants. The thiol compounds, including sodium hydrosulfide (NaHS) and cysteine, were found to effectively transform CCl4. The transformation of CCl4 followed pseudo-first-order kinetics, and the pseudo-first-order rate constants (kobs) were (3.24 +/- 0.46) x 10(-7) and 1.04 x 10(-7) s(-1), respectively, when solutions contained NaHS and cysteine alone. Addition of quinone compounds, including anthraquinone-2,6-disulfonate (AQDS), benzoquinone (BQ), juglone (JQ), naphthoquinone (NQ), lawsone (LQ), and menadione (MQ), increased the transformation rate and efficiency of CCl4. The kobs values for CCl4 transformation in the presence of quinones were 2.6-71 times higher than those for the thiol compounds alone. The enhancement efficiency followed the order JQ > NQ > BQ > AQDS > LQ > MQ. Spectroscopic studies indicated that the quinone compounds generated various active electron-transfer mediators to transfer electrons from the bulk reductants to CCl4. BQ and NQ produced mercaptoquinones as active redox mediators that significantly enhanced the transformation rate of CCl4 in the presence of NaHS. The addition of thiol reductants produced large amounts of AQDS semiquinone radical as the electron shuttle. In addition, MQ and LQ were reduced by NaHS to give hydroquinone, which slightly enhanced the transformation efficiency of CCl4. These results clearly indicate that the enhanced efficiency of quinones for the transformation of chlorinated hydrocarbons is specifically related to the produced reactive species. Mercaptoquinone is a more active mediator than either semiquinone or hydroquinone for transferring electrons in a reducing environment containing thiol reductants. PMID:16245816

  17. Taurine reduction in anaerobic respiration of Bilophila wadsworthia RZATAU.

    PubMed Central

    Laue, H; Denger, K; Cook, A M

    1997-01-01

    Organosulfonates are important natural and man-made compounds, but until recently (T. J. Lie, T. Pitta, E. R. Leadbetter, W. Godchaux III, and J. R. Leadbetter. Arch. Microbiol. 166:204-210, 1996), they were not believed to be dissimilated under anoxic conditions. We also chose to test whether alkane- and arenesulfonates could serve as electron sinks in respiratory metabolism. We generated 60 anoxic enrichment cultures in mineral salts medium which included several potential electron donors and a single organic sulfonate as an electron sink, and we used material from anaerobic digestors in communal sewage works as inocula. None of the four aromatic sulfonates, the three unsubstituted alkanesulfonates, or the N-sulfonate tested gave positive enrichment cultures requiring both the electron donor and electron sink for growth. Nine cultures utilizing the natural products taurine, cysteate, or isethionate were considered positive for growth, and all formed sulfide. Two clearly different pure cultures were examined. Putative Desulfovibrio sp. strain RZACYSA, with lactate as the electron donor, utilized sulfate, aminomethanesulfonate, taurine, isethionate, and cysteate, converting the latter to ammonia, acetate, and sulfide. Strain RZATAU was identified by 16S rDNA analysis as Bilophila wadsworthia. In the presence of, e.g., formate as the electron donor, it utilized, e.g., cysteate and isethionate and converted taurine quantitatively to cell material and products identified as ammonia, acetate, and sulfide. Sulfite and thiosulfate, but not sulfate, were utilized as electron sinks, as was nitrate, when lactate was provided as the electron donor and carbon source. A growth requirement for 1,4-naphthoquinone indicates a menaquinone electron carrier, and the presence of cytochrome c supports the presence of an electron transport chain. Pyruvate-dependent disappearance of taurine from cell extracts, as well as formation of alanine and release of ammonia and acetate, was detected. We suspected that sulfite is an intermediate, and we detected desulfoviridin (sulfite reductase). We thus believe that sulfonate reduction is one aspect of a respiratory system transferring electrons from, e.g., formate to sulfite reductase via an electron transport system which presumably generates a proton gradient across the cell membrane. PMID:9143131

  18. New strategies and building blocks for functionalised 9,10-bis(1,3-dithiol-2-ylidene)-9,10-dihydroanthracene derivatives, including pyrrolo-annelated derivatives and pi-extended systems with intramolecular charge-transfer.

    PubMed

    Christensen, Christian A; Bryce, Martin R; Batsanov, Andrei S; Becher, Jan

    2003-02-01

    A range of new functionalised 9,10-bis(1,3-dithiol-2-ylidene)-9,10-dihydroanthracene (TTFAQ) derivatives have been synthesised from the key di(halomethyl) building blocks, 10-[4,5-bis(bromomethyl)-1,3-dithiol-2-ylidene]-anthracene-9(10H)-one 10, 10-[4,5-bis(chloromethyl)-1,3-dithiol-2-ylidene]anthracene-9(10H)-one 11 and 9-[4,5-bis(chloromethyl)-1,3-dithiol-2-ylidene]-10-[4,5-bis(hexylsulfanyl)- 1,3-dithiol-2-ylidene]-9,10-dihydroanthracene 18. A Diels-Alder strategy comprising trapping of the transient exocyclic diene 19, which is derived from 18, with 1,4-naphthoquinone leads to the aromatised TTFAQ anthraquinone system 21. Horner-Wadsworth-Emmons olefination of 21 with the anion generated from reagent 22 gave the fused bis(TTFAQ) structure 23. Pyrrolo-annelated derivatives 30-34 have been obtained in a sequence of reactions from compound 10. Mono-formylation of the pyrrole ring of 32 and 33 under Vilsmeier conditions gave 35 and 36 which upon reaction with 2,4,5,7-tetranitrofluorene gave the donor-pi-acceptor diads 38 and 39. Cyclic voltammetry (CV) in solution for all the TTFAQ derivatives shows the typical quasi-reversible two-electron oxidation wave of the TTFAQ core at potentials which vary slightly depending on the substituents. For example, the value of Eox is raised by the electron withdrawing anthraquinone and tetranitrofluorene units of 21 and 38, respectively. The CV of the conjugated TTFAQ dimer 23 showed two, two-electron oxidation waves corresponding to the sequential formation of 23(2+) and 23(4+) (delta Eox = 130 mV) providing evidence for a significant intramolecular electronic interaction, i.e. the dication 23(2+) acts as a conjugated donor-pi-acceptor diad, thereby raising the oxidation potential of its partner TTFAQ unit. Spectroelectrochemical studies on 23 support this explanation. A strong intramolecular charge transfer band at lambda max 538 nm is seen in the UV-Vis spectra of the TTFAQ-pi-tetranitrofluorene diads 38 and 39. The X-ray crystal structures are reported for compounds 30, 33 and 34. The pyrrolo-TTFAQ moiety adopts a saddle-shape with the central ring of the dihydroanthracene moiety folded along the C(9) ... C(10) vector in each case. Significant intermolecular interactions are observed in the structures. PMID:12926254

  19. Genetic toxicity of naphthalene: a review.

    PubMed

    Schreiner, Ceinwen A

    2003-01-01

    Results of five previously unpublished studies of the genotoxicity of naphthalene are presented and extensively discussed in relation to the large database that exists in the published literature. According to the published literature, naphthalene has not induced gene mutations in bacterial assays or in a metabolically competent human cell line. However, naphthalene has caused cytotoxicity in some cell lines, and induced clastogenicity in Chinese hamster ovary (CHO) cells, in a human lymphoblastoid cell line, and in preimplantation mouse embryos. Some naphthalene metabolites were cytotoxic, but only naphthoquinones produced chromosomal damage in vitro. No chromosomal damage was observed in vivo in bone marrow erythrocytes from treated mice; however, a positive response was reported in a Drosophila assay for wing somatic mutation and recombination. The five unpublished studies of naphthalene genotoxicity include three studies in vitro (two Ames bacterial assays and an in vitro unscheduled DNA synthesis assay) and two in vivo (mouse micronucleus and in vivo unscheduled DNA synthesis). Naphthalene was inactive in all five studies, in agreement with reports in the published literature. Chronic inhalation of naphthalene over 2 yr induced an increased incidence of benign alveolar/bronchial adenomas in female mice, and nasal epithelial tumors in both sexes of rats. Inflammation, tissue damage, and subsequent regenerative hyperplasia at target organ sites occurred in both species. Results of standard genetic toxicity assays suggest that naphthalene is not likely to be genotoxic in vivo. Since the in vitro results come primarily from assays utilizing liver-mediated activation systems, and the in vivo results come from rodent organs that are not targets for tumors, tests using naphthalene-sensitive rodent tissues would determine the applicability of current data in addressing the mechanisms of these species and site-specific cancers. The standard assays reported here may be useful in predicting potential health hazard in other species, or in humans, in whom there are few reported instances of naphthalene-induced cancer, especially as more data on species-specific differences in naphthalene metabolism become available. Despite present data limitations, a threshold mechanism for tumorigenesis can be proposed. The absence of naphthalene-induced gene mutation and the presence of cytotoxicity and some chromosomal events in vitro are consistent with a threshold-related mechanism of tumor induction, driven by cytotoxicity and cell regeneration, followed by genetic events, or by accumulation of naphthalene at specific target sites to allow in situ formation of a genotoxic metabolite to trigger or enhance spontaneous tumor development. PMID:12554433

  20. Kinetics of redox interaction between substituted quinones and ascorbate under aerobic conditions.

    PubMed

    Roginsky, V A; Barsukova, T K; Stegmann, H B

    1999-07-01

    One-electron reduction of quinones (Q) by ascorbate (AscH ); (1) AscH + Q --> Q*- + Asc*- + H+, followed by the oxidation of semiquinone (Q*-) by molecular oxygen; (2) Q*- + O2 --> Q + O2*-, results in the catalytic oxidation of ascorbate (with Q as a catalyst) and formation of active forms of oxygen. Along with enzymatic redox cycling of Q. this process may be related to Q cytotoxicity and underlie an antitumor activity of some Qs. In this work, the kinetics of oxygen consumption accompanied the interaction of ascorbate with 55 Qs including substituted 1,4- and 1,2-benzoquinones, naphthoquinones and other quinoid compounds were studied in 50 mM sodium phosphate buffer, pH 7.40, at 37 degrees C by using the Clark electrode technique. The capability of Q to catalyze ascorbate oxidation was characterized by the effective value of kEFF calculated from the initial rate of oxygen consumption (R(OX)) by the equation R(OX) = kEFF[Q][AscH-] as well as by a temporary change in R(OX). The correlation of kEFF with one-electron reduction potential, E(Q/Q*-), showed a sigma-like plot, the same for different kinds of Qs. Only the Qs which reduction potential E(Q/Q*-) ranged from nearly -250 to + 50 mV displayed a pronounced catalytic activity, kEFF increased with shifting E(Q/Q*-) to positive values. The following linear correlation between kEFF (in M (-1) s(-1)) and E(Q/Q*-) (in mV) might be suggested for these Qs: lg(kEFF)= 3.91 + 0.0143E(Q/Q*-). In contrast, Qs with E(Q/Q*-) < - 250 mV and E(Q/Q*-) > + 50 mV showed no measurable catalytic activity. The Qs studied displayed a wide variety in the kinetic regularities of oxygen consumption. When E(Q/Q*-) was more negative than - 100 mV, Q displayed a simple ('standard') kinetic behavior--R(OX) was proportional to [AscH-][Q] independently of concentration of individual reagents, [AscH-] and [Q]; R(OX) did not decrease with time if [AscH-] was held constant: Q recycling was almost reversible. Meanwhile, Qs with E(Q/Q*-) > - 100 mV demonstrated a dramatic deviation from the 'standard' behavior that was manifested by the fast decrease in R(OX) with time and non-linear dependence of even starting values of R(OX) on [Q] and [AscH-]. These deviations were caused basically by the participation of Q*- in side reactions different from (2). The above findings were confirmed by kinetic computer simulations. Some biological implications of Q-AscH- interaction were discussed. PMID:10418963

  1. Dimeric Fe (II, III) complex of quinoneoxime as functional model of PAP enzyme: Mössbauer, magneto-structural and DNA cleavage studies

    NASA Astrophysics Data System (ADS)

    Salunke-Gawali, Sunita; Ahmed, Khursheed; Varret, François; Linares, Jorge; Zaware, Santosh; Date, Sadgopal; Rane, Sandhya

    2008-07-01

    Purple acid phosphatase, ( PAP), is known to contain dinuclear Fe2 + 2, + 3 site with characteristic Fe + 3 ? Tyr ligand to metal charge transfer in coordination. Phthiocoloxime (3-methyl-2-hydroxy-1,4-naphthoquinone-1-oxime) ligand L, mimics (His/Tyr) ligation with controlled and unique charge transfers resulting in valence tautomeric coordination with mixed valent diiron site in model compound Fe-1: [?-OH-Fe2 + 2, + 3 ( o-NQCH3ox) ( o-NSQCH3ox)2 (CAT) H2O]. Fe-2: [Fe + 3( o-NQCH3ox) ( p-NQCH3ox)2]2 a molecularly associated dimer of phthiocoloxime synthesized for comparison of charge transfer. 57Fe Mössbauer studies was used to quantitize unusual valences due to ligand in dimeric Fe-1 and Fe-2 complexes which are supported by EPR and SQUID studies. 57Fe Mössbauer spectra for Fe-1 at 300 K indicates the presence of two quadrupole split asymmetric doublets due to the differences in local coordination geometries of [Fe + 3]A and [Fe + 2]B sites. The hyperfine interaction parameters are ? A = 0.152, (? E Q)A = 0.598 mm/s with overlapping doublet at ? B = 0.410 and (? E Q)B = 0.468 mm/s. Due to molecular association tendency of ligand, dimer Fe-2 possesses 100% Fe + 3(h.s.) hexacoordinated configuration with isomer shift ? = 0.408 mm/s. Slightly distorted octahedral symmetry created by NQCH3ox ligand surrounding Fe + 3(h.s.) state generates small field gradient indicated by quadrupole split ? E Q = 0.213 mm/s. Decrease of isomer shifts together with variation of quadrupole splits with temperature in Fe-1 dimer compared to Fe-2 is result of charge transfers in [Fe2 + 2, + 3 SQ] complexes. EPR spectrum of Fe-1 shows two strong signals at g 1 = 4.17 and g 2 = 2.01 indicative of S = 3/2 spin state with an intermediate spin of Fe + 3(h.s.) configuration. SQUID data of ? _m^{corr} .T were best fitted by using HDVV spin pair model S = 2, 3/2 resulting in antiferromagnetic exchange ( J = -13.5 cm - 1 with an agreement factor of R = 1.89 × 10 - 5). The lower J value of antiferromagnetic exchange leads to Fe+3?-(OH) Fe + 2 bridging in Fe-1 dimer instead of ?-oxo bridge. The intermolecular association through H-bonds may lead to weakly coupled antiferromagnetic interaction between two Fe-2 molecules having Fe + 3(h.s.) centers. Using S = 5/2, 5/2 spin pair model we obtained best-fitted parameters such as J = -12.4 cm - 1, g = 2.3 with R = 3.58 × 10 - 5. Synthetic strategy results in non-equivalent iron sites in Fe-1 dimer analogues to PAP enzyme hence its reconstitution results in pUC-19 DNA cleavage activity, as physiological functionality of APase. It is compared with nuclease activity of Fe-2 RAPase.