- A versatile synthesis of the 1,4-dihydroxynaphthoquinone nucleus
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The electrochemical oxidation of different methoxynaphthalenes to afford the corresponding 5,8-dihydroxy-1,4-naphthoquinones has been examined. This method constitutes a new alternative and efficient route for the synthesis of the 5,8-dihydroxy-1,4-naphthoquinone nucleus. (C) 2000 Elsevier Science Ltd.
- Menegazzo,Sandona,Moro,Sheeba,Zagotto
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- A hydrogen peroxide-activated Cu(II) pro-ionophore strategy for modifying naphthazarin as a promising anticancer agent with high selectivity for generating ROS in HepG2 cells over in L02 cells
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Targeting redox vulnerability of cancer cells by pro-oxidants capable of generating reactive oxygen species (ROS) has surfaced as an important anticancer strategy. Due to the intrinsic narrow therapeutic window and other dangerous side effects of ROS generation, it is highly needed and challenging to develop pro-oxidative anticancer agents (PAAs) with high selectivity for generating ROS in cancer cells. Herein we report a hydrogen peroxide (H2O2)-activated Cu(II) pro-ionophore strategy to develop naphthazarin (Nap) as such type of PAAs based on the H2O2-mediated conversion of boronate to free phenol. The boronate-protected Nap (PNap) can exploit increased levels of H2O2 in HepG2 cells to in situ release Nap followed by its efflux via conjugation with reduced glutathione (GSH), allowing that the Nap-GSH adduct works as a Cu(II) ionophore to induce continuously GSH depletion via a reduction-dependent releasing of Cu(I) by GSH. This strategy endows PNap with the unprecedented ability to hit multi-redox characteristics (increased levels of H2O2, GSH and copper) of HepG2 cells, leading to ROS generation preferentially in HepG2 cells along with their selective death.
- Bao, Xia-Zhen,Wang, Qi,Ren, Xiao-Rong,Dai, Fang,Zhou, Bo
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p. 597 - 608
(2019/12/25)
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- The design of 1,4-naphthoquinone derivatives and mechanisms underlying apoptosis induction through ROS-dependent MAPK/Akt/STAT3 pathways in human lung cancer cells
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The natural compound 1,4-naphthoquinone has potent anti-tumor activity. However, the clinical application of 1,4-naphthoquinone and its derivatives has been limited by their side effects. In this study, we attempted to reduce the toxicity of 1,4-naphthoquinone by synthesizing two derivatives: 2,3-dihydro-2,3-epoxy-2-propylsulfonyl-5,8-dimethoxy-1,4-naphthoquinone (EPDMNQ) and 2,3-dihydro-2,3-epoxy-2-nonylsulfonyl-5,8-dimethoxy-1,4-naphthoquinone (ENDMNQ). Then we evaluated the cytotoxicity and molecular mechanisms of these compounds in lung cancer cells. EPDMNQ and ENDMNQ significantly inhibited the viabilities of three lung cancer cell lines and induced A549 cell cycle arrest at the G1 phase. In addition, they induced the apoptosis of A549 lung cancer cells by increasing the phosphorylation of p38 and c-Jun N-terminal kinase (p-JNK), and decreasing the phosphorylation of extracellular signal-related kinase (p-ERK), protein kinase B (Akt), and signal transducer and activator of transcription 3 (STAT3). Furthermore, they increased reactive oxygen species (ROS) levels in A549 cells; however, pretreatment with the ROS inhibitor N-acetyl-L-cysteine significantly inhibited EPDMNQ- and ENDMNQ-mediated apoptosis and reversed apoptotic proteins expression. In conclusion, EPDMNQ and ENDMNQ induced G1 phase cell cycle arrest and apoptosis in A549 cells via the ROS-mediated activation of mitogen activated protein kinase (MAPK), Akt and STAT3 signaling pathways.
- Zhang, Yi,Luo, Ying-Hua,Piao, Xian-Ji,Shen, Gui-Nan,Wang, Jia-Ru,Feng, Yu-Chao,Li, Jin-Qian,Xu, Wan-Ting,Zhang, Yu,Zhang, Tong,Wang, Chang-Yuan,Jin, Cheng-Hao
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p. 1577 - 1587
(2019/03/06)
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- The compound 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via reactive oxygen species-regulated mitogen-activated protein kinase, protein kinase B, and signal transducer and activator of transcription 3 signaling in human gastric cancer cells
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(Table presented.). It is reported that 1,4-naphthoquinones and their derivatives have potent antitumor activity in various cancers, although their clinical application is limited by observed side effects. To improve the therapeutic efficacy of naphthoquinones in the treatment of cancer and to reduce side effects, we synthesized a novel naphthoquinone derivative, 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ). In this study, we explored the effects of NTDMNQ on apoptosis in gastric cancer cells with a focus on reactive oxygen species (ROS) production. Our results demonstrated that NTDMNQ exhibited the cytotoxic effects on gastric cancer cells in a dose-dependent manner. NTDMNQ significantly induced mitochondrial-related apoptosis in AGS cells and increased the accumulation of ROS. However, pre-treatment with N-acetyl-L-cysteine (NAC), an ROS scavenger, inhibited the NTDMNQ-induced apoptosis. In addition, NTDMNQ increased the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and Signal Transducer and Activator of Transcription 3 (STAT3); these effects were blocked by mitogen-activated protein kinase (MAPK) inhibitor and NAC. Taken together, the present findings indicate that NTDMNQ-induced gastric cancer cell apoptosis via ROS-mediated regulation of the MAPK, Akt, and STAT3 signaling pathways. Therefore, NTDMNQ may be a potential treatment for gastric cancer as well as other tumor types.
- Wang, Jia-Ru,Shen, Gui-Nan,Luo, Ying-Hua,Piao, Xian-Ji,Shen, Meng,Liu, Chang,Wang, Yue,Meng, Ling-Qi,Zhang, Yi,Wang, Hao,Li, Jin-Qian,Xu, Wan-Ting,Liu, Yang,Sun, Hu-Nan,Han, Ying-Hao,Jin, Mei-Hua,Cao, Long-Kui,Jin, Cheng-Hao
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p. 295 - 306
(2018/09/25)
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- Ruthenium-catalyzed C-H oxygenation of quinones by weak O-coordination for potent trypanocidal agents
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Ruthenium-catalysis enabled the C-5 selective C-H oxygenation of naphthoquinones, and also sets the stage for the site-selective introduction of a hydroxyl group into anthraquinones. A-ring modified naphthoquinoidal compounds represent an important class of bioactive quinones for which the present study encompasses the first C-H oxygenation strategy by weak O-coordination.
- Dias, Gleiston G.,Rogge, Torben,Kuniyil, Rositha,Jacob, Claus,Menna-Barreto, Rubem F. S.,Da Silva Júnior, Eufranio N.,Ackermann, Lutz
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supporting information
p. 12840 - 12843
(2018/11/30)
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- Method for synthesizing 5,8-dihydroxy-1,4-naphthoquinone with molten salt method
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The invention discloses a method for synthesizing 5,8-dihydroxy-1,4-naphthoquinone with a molten salt method. The method comprises the following main steps: step 1, a complex of 5,8-dihydroxy-1,4-naphthoquinone and AlCl3 is formed from hydroquinone and maleic anhydride as raw materials for synthesizing 5,8-dihydroxy-1,4-naphthoquinone as well as anhydrous AlCl3 as a catalyst and NaCl as molten salt through Friedel-Crafts acylation at high temperature and high pressure; step 2, free 5,8-dihydroxy-1,4-naphthoquinone is prepared from the complex of 5,8-dihydroxy-1,4-naphthoquinone and AlCl3 by digesting and then purified, and a 5,8-dihydroxy-1,4-naphthoquinone product is obtained. According to the method, the target product is obtained directly with one-step reaction on the basis of the molten salt method without an intermediate, so that the synthetic route is shortened greatly, aftertreatment is simple, a recrystallization step can be omitted, and extraction purity is guaranteed.
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Paragraph 0028-0031; 0033-0042
(2018/04/01)
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- Synthesis of naphthazarin derivatives and identification of novel thioredoxin reductase inhibitor as potential anticancer agent
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Mammalian thioredoxin reductase (TrxR) enzymes play a crucial role in regulating multiple redox-based signaling pathways and have attracted increasing attention as promising anticancer drug targets. We report here the synthesis of a panel of naphthazarin derivatives and discovery of 2-methyl-5,8-dihydroxy-1,4-naphthoquinone (3, 2-methylnaphthazarin) as a potent cytotoxic agent with a submicromolar half maximal inhibitory concentration to the human promyelocytic leukemia HL-60 cells. Mechanism studies reveal that the compound selectively inhibits TrxR to induce oxidative stress-mediated apoptosis of HL-60 cells. Knockdown of TrxR sensitizes the cells to 3 insults, while overexpression of the functional enzyme confers resistance to the compound treatment, underpinning the physiological significance of targeting TrxR by 3. Clarification of the interaction of compound 3 with TrxR unveils a mechanism underlying the cellular action of the compound, and sheds light in considering development of the compound as a potential cancer chemotherapeutic agent.
- Zhang, Junmin,Liu, Yaping,Shi, Danfeng,Hu, Guodong,Zhang, Baoxin,Li, Xinming,Liu, Ruijuan,Han, Xiao,Yao, Xiaojun,Fang, Jianguo
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p. 435 - 447
(2017/10/09)
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- Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: a structure–activity relationship study
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The synthesis of 1,4-naphthoquinone derivatives is of great interest since these compounds exhibit strong activity as antimalarial, antibacterial, antifungal and anticancer agents. A series of 50 naphthoquinone derivatives was synthesized and evaluated for antibacterial and antifungal activity against Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida krusei, Candida parapsilosis and Cryptococcus neoformans using the broth microdilution method. The Candida species were the most susceptible microorganisms. Halogen derivatives of 1,4-naphthoquinone presented strong activity, e.g., 2-bromo-5-hydroxy-1,4-naphthoquinone, which exhibited inhibition at an MIC of 16?μg/mL in S. aureus, and 2-chloro-5,8-dihydroxy-1,4-naphthoquinone, with an MIC of 2?μg/mL in C. krusei. These compounds showed higher activity against fungi, but the antibacterial activities were very low. The study of structure–activity relationships is very important in the search for new antimicrobial drugs due to the limited therapeutic arsenal.
- Sánchez-Calvo, Juan M.,Barbero, Gara R.,Guerrero-Vásquez, Guillermo,Durán, Alexandra G.,Macías, Mariola,Rodríguez-Iglesias, Manuel A.,Molinillo, José M. G.,Macías, Francisco A.
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p. 1274 - 1285
(2016/07/06)
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- A convenient and efficient synthesis of naphthazarin
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A convenient and efficient synthetic method of the important intermediate naphthazarin is presented starting from 1, 4, 5, 8-tetramethoxynaphthalene in an overall yield of 87%. Compared with the reported synthesis, this method has several advantages. Firstly, the reaction conditions are milder; secondly, the workup of each step is simpler and the yield is considerably higher; thirdly, all the reactions involved in the method are more suitable for large-scale preparations.
- Peng, Ying,Zhou, Wen,Zhang, Min,Wang, Cheng-Dong,Chen, Qian,Jiang, Sheng-Jie,Li, Shao-Shun
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- The treatment of pests using substituted naphthoquinones
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Naphthoquinone compounds of the formula I wherein R1 and R2 are each, independently, selected from H and OH and R3 and R4 are each, independently, selected from H, halo and 1-4C alkyl groups, provided that when R1 and R2 are each H, R3 and R4 cannot both be H, have use as pesticides particularly in the treatment of acarids and insects. A pesticidal composition comprises at least one compound of the formula I together with an inert carrier.
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- Colorant precursors derivable from cells of plants of the genus medicago, process for their preparation and use thereof for the preparation of colorants
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Colorant precursors, which are present in the cells of plants belonging to the genus Medicago, such as alfalfa, can react with quinones so as to yield colorants which can be used in dyeing compositions for textiles or hair.
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- The reductive dehalogenation of halosubstituted naphthazarins and quinizarins as a simple route to parent compounds
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By the reaction of 2-chloro-3-alkyl-, 2,3-dichloro(dibromo)-, trichloro(tribromo)-and tetrachloro(tetrabromo)-naphthazarins and 2,3- dichloroquinizarin with Fe/HOAc followed by oxidation with an air in a mild basic conditions the corresponding naphthazarins and quinizarin were obtained in good to excellent yields.
- Anufriev, Victor Ph.,Malinovskaya, Galina V.,Novikov, Vyacheslav L.,Balanyova, Nadezhda N.,Polonik, Sergey G.
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p. 2149 - 2157
(2007/10/03)
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- Thermodynamics of semiquinone disproportionation in aqueous buffer
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The thermodynamic parameters, Kdisp, ΔH° and ΔS°, controlling the disproportionation of semiquinones derived from 1,4-benzoquinone (BQ), 1,4-naphthoquinone (NQ), 2-methylbenzoquinone (MBQ), menadione (MNQ), naphthazarin (NZQ) and quinizarin (QNZ), have been determined. Smaller disproportionation constants, Kdisp, are observed upon addition of a fused benzene ring to the semiquinone structure. Negative enthalpies and positive entropies of disproportionation govern the disproportionation equilibria. Addition of OH groups to the 5 and 8 positions in NQ?- displaces the disproportionation equilibrium to the semiquinone probably due to intramolecular hydrogen bonding.
- Alegria, Antonio E.,Lopez, Marcos,Guevara, Norberto
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p. 4965 - 4968
(2007/10/03)
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- Method for dyeing keratinous fibres using a monohydroxyindole or dihydroxyindole and a non-oxidizing aromatic carbonyl derivative and dyeing agent
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The present invention relates to a method for dyeing keratinous fibers, characterized in that the following are applied to the fibers: a) a composition (A) containing, in a medium appropriate for dyeing, at least one monohydroxyindole or dihydroxyindole, this application being preceded or followed by the application of b) a composition (B) containing, in a medium appropriate for dyeing, at least one aromatic carbonyl derivative chosen from hydroxyacetophenones, hydroxybenzophenones, 2-hydroxy-1,4-benzoquinones, hydroxy-1,4-naphthoquinones,amino-1,4-naphthoquinones,hydroxy-9,10-anthraquinones and amino-9,10-anthraquinones. It also relates to the dyeing agents for carrying it out.
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- A Direct Route for the Regioselective Synthesis of Hydroxylated Aromatic Cycloalkanediones
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A "one-pot" regioselective synthesis of hydroxylated aromatic cycloalkanediones 1 from phenols or their methyl ethers and aliphatic dicarboxylic acid chlorides is reported.
- Sartori, Giovanni,Bigi, Franca,Goffredi, Gino,Maggi, Raimondo,Portioli, Roberto,Casnati, Giuseppe
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p. 2061 - 2079
(2007/10/02)
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- Pigments of Fungi. XXII Synthesis of (+/-) Austrocortirubin and Related Tetrahydroanthraquinones
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The fungal tetrahydroanthraquinones austrocortirubin (1) and austrocortilutein (3) and their deoxy derivatives (2) and (4), respectively, are synthesized in racemic form from naphthopurpurin (6).
- Burns, Christopher J.,Gill, Melvyn
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p. 1447 - 1458
(2007/10/02)
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- Absorption Spectra of the Radical Ions of Quinones: A Pulse Radiolysis Study
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The formation of quinone radical ions was observed at room temperature using pulse radiolysis.The following quinones were investigated: p-benzoquinone, p-naphthoquinone, 5,8-dihydroxy-1,4-naphthoquinone, anthraquinone and 1,4-dihydroxyanthraquinone.The radial cations were produced in freon-113 solutions and the radical anions were produced in methanol solutions.Th absorption spectra of the radical ions were found in the near -UV-VIS range.The spectra of the radical cations were blue shifted compared with the spectra of the corresponding radical anions.
- Mayer, Jozef,Krasiukianis, Roman
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p. 2943 - 2947
(2007/10/02)
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- N.M.R. Study of Bond Orders in o- and p-Quinones
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The 4J(Me-CC-H) coupling constsnt, previously established as a probe of bond order,1-3 was used to examine bond orders in a number of quinones.It was found that the presence of a quinone moiety does not cause bond localization in aromatic rings adjacent to the quinone ring.
- Gready, Jill E.,Hata, Kazumi,Sternhell, Sever,Tansey, Charles W.
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p. 593 - 600
(2007/10/02)
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- Enthalpies of combustion of 1,4-naphthoquinone, 9,10-anthraquinone, 9,10-phenanthraquinone, 1,4,9,10-anthradiquinone, 5,8-dihydroxy-1,4-naphthoquinone, and 1,4-dihydroxy-9,10-anthraquinone
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The standard (p0 = 0.1 MPa) molar enthalpies of combustion in oxygen at 298.15 K were measured by static-bomb calorimetry for some quinones and dihydroxyquinones.The standard molar enthalpies of sublimation at 298.15 K were measured by microcalorimetry for 1,4-naphthoquinone and 9,10-phenanthraquinone; values were selected from the literature for the remaining compounds in order to derive the standard molar enthalpies of formation in the gaseous state. The energies of the intramolecular hydrogen bonds in the dihydroxyquinones were assessed as (25 +/- 3) kJ*mol-1. 1,4,9,10-Anthradiquinone is apparently considerably strained, and although its reaction with water produces 1,4-dihydroxy-9,10-anthraquinone, a concomitant formation of hydrogen peroxide is shown to be thermodynamically improbable.
- Silva, M. A. V. Ribeiro da,Silva, Maria D. M. C. Ribeiro da,Teixeira, J. A. S.,Bruce, J. M.,Guyan, Patricia M.,Pilcher, G.
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p. 265 - 274
(2007/10/02)
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- The 2- or 6-(α-Hydroxyalkyl- and α-Oxoalkyl)-5,8-dimethoxy-1,4-naphtoquinones from the Oxidative Demethylation of 2-(α-Hydroxyalkyl- and α-Oxoalkyl)-1,4,5,8-tetramethoxynaphthalenes with Cerium(IV) Ammonium Nitrate, and the Further Demethylations to Naphthazarins
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Oxidative demethylation of 2-(α-hydroxyalkyl- and α-oxoalkyl)-1,4,5,8-tetramethoxynaphthalene with (NH4)2Ce(NO3)6 gave two isomeric dimethoxynaphthoquinones: 2-substituted and 6-substituted 5,8-dimethoxy-1,4-naphthoquinones.Further demethylations of the former isomer to the corresponding dihydroxynaphthoquinones required an AgO-40percentHNO3 reagent, while the latter isomers needed AlCl3 as the demethylation reagent.Some comments regarding the mechanism of these oxidative demethylations with (NH4)2Ce(NO3)6 are given.
- Tanoue, Yasuhiro,Terada, Akira
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p. 2039 - 2046
(2007/10/02)
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- Nouvelles methodes de synthese de la naphtopurpurine (trihydroxy-2,5,8 naphtoquinone-1,4)
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The condensation of 1,2,4 trimethoxybenzene with maleic anhydride in the presence of AlCl3-NaCl affords, in a single step, naphtopurpurine 1, an important intermediate in the synthesis of naphtoquinone derived natural products.A different synthesis of compound 1 consists in the substitution of the halogen atom in 2-chloro or 2-bromo-naphthazirin by a methoxy group which is subsequently cleaved in an acidic medium or by a Lewis acid.
- Bekaert, Alain,Andrieux, Jean,Plat, Michel
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p. 314 - 316
(2007/10/02)
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- Site-Selective Diels-Alder Reactions of 1,4,5,8-Naphthodiquinones with Anthracenes and Successively with Cyclopentadiene: Electronic Effects vs. Steric Effects
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The cycloaddition reactions of naphthodiquinones with anthracene derivatives have been investigated.While anthracene (4) reacted with naphthodiquinones (1,2, and 13) at the internal double bond to give the internal adducts (6,7, and 14), the reaction of 9,10-substituted anthracenes (5) took place at the terminal double bond to afford the terminal adducts (8,9, and 15).The successive reaction of adducts 6 and 7 with cyclopentadiene gave the Diels-Alder adducts 16 and 17, respectively, which were photochemically converted into the cage compounds 18 and 19 in high yields.The reaction of 8 with cyclopentadiene afforded terminal adducts 20, whereas the similar reaction of 9 gave internal adducts 21 which were smoothly converted on irradiation to the cage compounds 22.The site selectivity in these reactions was discussed on the basis of the frontier molecular orbital (FMO) analysis as well as consideration of the steric effects of the substituents.
- Hayakawa, Kenji,Aso, Mariko,Kanematsu, Ken
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p. 2036 - 2040
(2007/10/02)
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- Electron-Transfer Kinetics of Quinones at Solid Electrodes in Aprotic Solvents at Low Temperatures
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Activation paramaters for the electrochemical one-electron reduction of quinones were evaluated at glassy carbon, Au, and Pt electrodes from 170 to 290 K in aprotic solvents (N,N-dimethylformamide and propionitrile) by cyclic voltametry.Systematic differences in the activation parameters among electrode materials were observed.The average of the activation enthalpy was 13 +/- 2 kJ /mol for the glassy arbon electrode, 21 +/- 3 kJ/mol for the Au electrode, and 14 +/- 4 kJ/mol for the Pt electrode in N,n-dimethylformamide, showing that the extent of the interaction between the electrode surface and the reactant is different for each electrode material.The Arrheneus plots for 1,4-benzoquinone curved down only at the glassy carbon electrode in both N,N-dimethylformamide and propionitrile, indicating that it was reduced by a different mechanism at law temperatures (250 K) at the glassy carbon electrode.The experimental techniques and a simple cooling system for low-temperature electrochemistry are also described.
- Nagaoka, Tsutomu,Okazaki, Satoshi
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p. 2340 - 2344
(2007/10/02)
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- Reduction of the Naphthazarin Molecule as Studied by Pulse Radiolysis Part 2. - Second One-electron Step
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The disproportionation of the radicals formed by one-electron reduction of naphthtazarin has been observed as a function of pH in the range 1-14.The radicals are least prone to disproportionate at pH 8-9, the stability constant at pH ca. 8.5 being 0.4.The data have been combined with the one-electron reduction potentials of naphthazarin to obtain the one-electron reduction potentials of the radicals (i.e. the second one electron reduction potential of the parent) as a function of pH.E17 of the radicals is equal to E27 of the parent and is -15 mV.The two-electron reduction potential of naphthazarin is -62 mV at pH7 and -351 mV at pH 0.The optical absorption spectra of 1,4,5,8-tetrahydroxynaphthalene prepared in different ionised forms by radiolysis and by chemical reduction have been determined.The redox data and the absorption spectra show that this compound has pKa values of 7.6 and 8.7 and has no further pKa values below ca. 14.
- Land, Edward J.,Mukherjee, Tulsi,Swallow, A. John,Bruce, J. Malcolm
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p. 405 - 416
(2007/10/02)
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- Oxidative Coupling. Part 11. Approaches to the Synthesis of Bikaverin
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The synthesis of orcinoylhydroquinones has been achieved by photochemical Fries rearrangement of their esters.A study of their oxidation (DDQ) shows that oxidative coupling occurs to produce a spirocyclohexenedione which can be thermally isomerised to the xanthone.The synthesis of a tetracyclic xanthone (related to bikaverin) is described.
- Lewis, John R.,Paul, John G.
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p. 770 - 775
(2007/10/02)
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