- Evaluation of a series of 9,10-anthraquinones as antiplasmodial agents
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Background: A phytochemical study on medicinal plants used for the treatment of fever and malaria in Africa yielded metabolites with potential antiplasmodial activity, many of which are Anthraquinones (AQ). AQs have similar sub-structure as naphthoquinones and xanthones, which were previously reported as novel antiplasmodial agents. Objective: The present study aimed to investigate the structural requirements of 9,10-anthraquinones with hydroxy, methoxy and methyl substituents to exert strong antiplasmodial activity and to investigate their possible mode of action. Methods: Thirty-one AQs were synthesized through Friedel-Crafts reaction and assayed for antiplasmodial activity in vitro against Plasmodium falciparum (3D7). The selected compounds were tested for toxicity and probed for their mode of action against β-hematin dimerization through HRP2 and lipid catalyses. The most active compounds were subjected to a docking study using AutoDock 4.2. Results: The active AQs have similar common structural characteristics. However, it is difficult to establish a structure-activity relationship as certain compounds are active despite the absence of the structural features exhibited by other active AQs. They have either ortho- or meta-arranged substituents and one free hydroxyl and/or carbonyl groups. When C-6 is substituted with a methyl group, the activity of AQs generally increased. 1,3-DihydroxyAQ (15) showed good antiplasmodial activity with an IC50 value of 1.08 μM, and when C-6 was substituted with a methyl group, 1,3-dihydroxy-6-methylAQ (24) showed stronger antiplasmodial activity with an IC50 value of 0.02μM, with better selectivity index. Compounds 15 and 24 showed strong HRP2 activity and mild toxicity against hepatocyte cells. Molecular docking studies showed that the hydroxyl groups at the ortho (23) and meta (24) positions are able to form hydrogen bonds with heme, of 3.49 A and 3.02 A, respectively. Conclusion: The activity of 1,3-dihydroxy-6-methylAQ (24) could be due to their inhibition against the free heme dimerization by inhibiting the HRP2 protein. It was further observed that the anthraquinone moiety of compound 24 bind in parallel to the heme ring through hydrophobic interactions, thus preventing crystallization of heme into hemozoin.
- Osman, Che Puteh,Ismail, Nor Hadiani,Widyawaruyanti, Aty,Imran, Syahrul,Tumewu, Lidya,Choo, Chee Yan,Ideris, Sharinah
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p. 353 - 363
(2019/06/20)
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- COLLAGEN MATRIX WITH LOCALLY CONTROLLED INTRAFIBRILLAR AND EXTRAFIBRILLAR MINERAL CONTENT AND METHODS OF PRODUCING
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A mineralized collagen matrix with an intrafibrillar and/or extrafibrillar gradient of mineralization for insertion replacement is disclosed. The intrafibrillar mineralization of the collagen matrix is formed by the addition of fetuin to the simulated body fluid. The gradient of intrafibrillar mineralization may stiffen the collagen matrix and simulate a natural insertion for improved cell infiltration and regeneration.
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Page/Page column
(2014/08/19)
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- Synthesis and antitumor activities of novel α-aminophosphonate derivatives containing an alizarin moiety
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A series of novel α-aminophosphonate derivatives containing an alizarin moiety (6-7) was designed and synthesized as antitumor agents. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay results indicated that most compounds exhibited moderate to high inhibitory activity against KB, NCI-H460, HepG 2, A549, MGC-803, Hct-116, CNE and Hela tumor cell lines. The action mechanism of representative compounds 7h, 7j and 7n were investigated by fluorescence staining assays, flow cytometric analysis and real-time polymerase chain reaction (PCR) assays, which indicated that these compounds induced apoptosis and involved G1 phase arrest by increasing the production of intracellular Ca2+ and reactive oxygen species (ROS) and affecting associated enzymes and genes. The results demonstrated that these compounds may induce apoptosis through a mitochondrion-dependent pathway.
- Ye, Man-Yi,Yao, Gui-Yang,Pan, Ying-Ming,Liao, Zhi-Xin,Zhang, Ye,Wang, Heng-Shan
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p. 116 - 128
(2014/07/08)
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- Total synthesis, cytotoxic effects of damnacanthal, nordamnacanthal and related anthraquinone analogues
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Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were synthesized with modified reaction steps and investigated for their cytotoxicity against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC 50 = 5.70 ± 0.21 and 8.50 ± 1.18 μg/mL), 2-hydroxymethyl-1,3-dimethoxyanthraquinone (6, IC50 = 12.10 ± 0.14 and 14.00 ± 2.13), 2-formyl-1,3-dimethoxyantharquinone (7, IC 50 = 13.10 ± 1.02 and 14.80 ± 0.74), 1,3-dimethoxy-2-methylanthraquinone (4, IC50 = 9.40 ± 3.51 and 28.40 ± 2.33), and 1,3-dihydroxy-2-methylanthraquinone (3, IC 50 = 25.60 ± 0.42 and 28.40 ± 0.79) also exhibited moderate cytotoxicity against MCF-7 and K-562 cancer cell lines, respectively. Other structurally related compounds like 1,3-dihydroxyanthraquinone (13a, IC50 = 19.70 ± 0.35 and 14.50 ± 1.28), 1,3-dimethoxyanthraquinone (13b, IC50 = 6.50 ± 0.66 and 5.90 ± 0.95) were also showed good cytotoxicity. The target compound damnacanthal (1) was found to be the most cytotoxic against the MCF-7 and K-562 cancer cell lines, with IC50 values of 3.80 ± 0.57 and 5.50 ± 1.26, respectively. The structures of all compounds were elucidated with the help of detailed spectroscopic techniques.
- Akhtar, Muhammad Nadeem,Zareen, Seema,Yeap, Swee Keong,Ho, Wan Yong,Lo, Kong Mun,Hasan, Aurangzeb,Alitheen, Noorjahan Banu
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p. 10042 - 10055
(2013/09/23)
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- An anthraquinone scaffold for putative, two-face bim BH3 α-helix mimic
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Bim BH3 peptide features an α-helix with hotspot residues on multiple faces. Compound 5 (6-bromo-2,3-dihydroxyanthracene-9,10-dione), which adopts a rigid-plan amphipathic conformation, was designed and evaluated as a scaffold to mimic two faces of Bim α-helix. It reproduced the functionalities of both D67 and I65 on two opposing helical sides. Moreover, it maintained the two-faced binding mode during further evolution. A putative BH3 α-helix mimic and nanomolar Bcl-2/Mcl-1 dual inhibitor, 6, was obtained based on the structure of 5.
- Zhang, Zhichao,Li, Xiangqian,Song, Ting,Zhao, Yan,Feng, Yingang
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p. 10735 - 10741
(2013/02/23)
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- Synthesis and activity of substituted anthraquinones against a human filarial parasite, Brugia malayi
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Lymphatic filariasis (elephantiasis) is a global public health problem caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. We have previously reported anthraquinones from daylily roots with potent activity against pathogenic trematode Schistosoma mansoni. Here we report the synthesis of novel anthraquinones A-S and their antifilrarial activity. Anthraquinones A-S were synthesized by a single-step Friedel-Crafts acylation reaction between phthalic anhydrides and substituted benzenes. The antifilarial properties of these synthetic anthraquinones were tested against microfilaria as well as adult male and female worms of B. malayi. The most active anthraquinone was K, which showed 100% mortality within 1, 5, and 3 days, respectively, against microfilaria and adult male and female worms at 5 ppm concentration. Albendazole, an oral drug currently used to treat parasitic infections, was used as a positive control. Methylated products of anthraquinones did not affect the microfilaria. Histological examination of treated adult female parasites showed most of the anthraquinones caused marked effects on intrauterine embryos.
- Dhananjeyan, Mugunthu R.,Milev, Youli P.,Kron, Michael A.,Nair, Muraleedharan G.
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p. 2822 - 2830
(2007/10/03)
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- Novel anthraquinones and process for the preparation and method of use thereof
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A process for the preparation of hydroxyl substituted anthraquinones is described. The process couples a phthalic anhydride (substituted or unsubstituted) to benzene ring moiety substituted with at least two hydroxyl groups. Remaining hydroxy groups were converted to methoxy groups in some anthraquinones. The compounds are particularly useful for the treatment of parasitic diseases. Also, a method of treating or preventing malaria, filariasis schistosomiasis and other parasitic diseases using anthraquinones.
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Page/Page column 4, 5
(2008/06/13)
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- Pathway of anthracene modification under simulated solar radiation
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Exposure of polycyclic aromatic hydrocarbons (PAHs) to sunlight results in rapid structural photomodification generally via oxidation reactions. These PAH modification products are in many cases more toxic than their parent compounds. In this study, anthracene (ANT), a rapidly photooxidized PAH, was irradiated with simulated solar radiation (SSR, 100 μmol m-2 s- 1) in aqueous solution to examine the photomodification pathway. The photoproducts formed were identified by HPLC. The ANT product profile after 9 h in SSR was very complex, with more than 20 compounds detected. The photoproducts formed were anthraquinones, benzoic acids, benzaldehydes and phenols showing the process to be oxidative in nature. Some of the anthraquinones were themselves subject to photooxidation, and were thus intermediates in the product pathway. The kinetics of ANT photooxidation revealed a pseudo first-order reaction with a half-life of 2 h under the SSR source used. The kinetics of product formation allowed deduction of a probable photomodification pathway. This study indicates that PAH photooxidation products are likely to exist as complex, dynamically changing mixtures in PAH contaminated aquatic environments.
- Mallakin, Ali,George Dixon,Greenberg, Bruce M.
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p. 1435 - 1441
(2007/10/03)
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- Different synthetic routes towards efficient organogelators: 2,3-substituted anthracenes
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Three synthetic approaches towards 2,3-substituted anthracenes are reported and discussed in terms of selectivity and viability. This allowed us to introduce a variety of substituents as sidearms. Promising results have been found using a tandem Diels-Alder aromatization reaction using 2,2,3-dimethoxybuladiene 9 as a key intermediate. However, for multigram preparations the Friedel-Crafts approach is preferred.
- Pozzo, Jean-Luc,Clavier, Gilles M.,Colomes, Michel,Bouas-Laurent, Henri
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p. 6377 - 6390
(2007/10/03)
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- 1H and 13C NMR studies of some anthraquinones and anthracenetetrones
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1H and 13C NMR chemical shifts are reported and assigned for 1,4,9,10- and 2,3,9,10-anthracenetetrone. In addition, NMR data are given for 2,3-dihydroxy-9, 10-anthraquinone, 2,3-dimethoxy-9,10-anthraquinone and 1-hydroxy-2-acetoxy-9,10-anthraquinone, encountered during the preparation of the anthracenetetrones.
- Danielsen,Francis,Aksnes
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p. 1043 - 1045
(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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- Vicarious Nucleophilic Hydroxylation of Aromatic Nitro Compounds with Organic Hydroperoxides
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Nitrobenzene, α-nitronaphthalene, m-dinitrobenzene, 1,3,5-trinitrobenzene, m-nitrobenzophenone, m-nitrobenzonitrile, methyl m-nitrobenzoate and m-nitro diphenylsulphone can be hydroxylated with cumene or tert-butyl hydroperoxide in dipolar aprotic solvents in the presence of strong bases.The hydroxyl group is introduced preferably in p-position to the nitro group.Attempts to hydroxylate benzophenone, anthraquinone, 2-ethyl anthraquinone, anthraquinone 2-sulphonate, benzonitrile and diphenyl sulphone under the same conditions failed. 1-Nitroanthraquinone delivered 1-hydroxy, 1,2-dihydroxy and 1,4-dihydroxy anthraquinone.
- Brose, Thomas,Holzscheiter, Felix,Mattersteig, Gunter,Pritzkow, Wilhelm,Voerckel, Volkmar
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p. 497 - 504
(2007/10/02)
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- A NEW METHODOLOGICAL APPROACH TO ANTHRAQUINONE AND ANTHRACYCLINONE SYNTHESIS
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A new general methodology for the anthraquinone and anthracyclinone synthesis has been developed.In contrast to the data reported in the previous literature, anthraquinones can be obtained under mild conditions from ortho dicarboxylic acid chlorides and suitable aromatic substrates via a Friedel-Crafts process.In this context the classic Wong synthesis of anthracyclinones has been greatly improved.The study of the reaction mechanism permitted the unexpected results to be rationalized and to account for the "ortho template bisacylation" of the phenol substrates.
- Sartori, Giovanni,Casnati, Giuseppe,Bigi, Franca,Foglio, Federica
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- ECOLOGICAL ASPECTS OF INDANTHRONE PRODUCTION.
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The authors describe certain procedures for diminishing the harmful effects of indanthrone (I) production on the environment. The purpose of this work was to develop an ecologically acceptable technology for production of Vat Blue 0, with shortening and intensification of stages of low efficiency. It was found that the determining factor in production of Vat Blue 0 is the ratio of the solvent to potassium hydroxide. Melt mobility is ensured by the KOH:H//2O ratio (KOH of 88 mass % concentration is in the liquid phase even at 100 degree ). The highest indanthrone yield is attained at 1:0. 17 ratio of KOH to triethylene glycol (TEG). At 1:1 component ratio indanthrone is not formed, while at 1:05 ratio the yield is not high.
- Sadchenko,Zinchenko,Bobrovskaya,Rogovik
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p. 1211 - 1214
(2007/10/02)
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- The photochemistry of 9,10-anthracenedione in sulfuric acid solution. The dependence of product yields on reaction conditions
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Irradiation of a sulfuric acid solution of 9,10-anthracenedione with near-uv light generated 2-hydroxy-9,10-anthracenedione as the major product.In addition, the 1-hydroxy and polyhydroxy derivatives and the reduction products anthrone and bianthronyl were also formed.The yields of these minor products were markedly influenced by the concentrations of water and oxygen in the sulfuric acid.At low light intensities, oxygen quenched the efficient formation of the hydroxyanthracenediones and also oxidised the initial quinone reduction products.Photoreduction of the anthracenedione and photooxidation of anthrone occurred simultaneously in the solution.The reaction mechanism is more complex than previous studies indicated.
- Broadbent, A. Douglas,Stewart, John M.
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p. 1965 - 1969
(2007/10/02)
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- Photochemical Hydroxylation of Anthracene-9,10-dione in Sulphuric Acid Solution
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Near u.v. irradiation of anthracene-9,10-dione in deoxygenated 96percent H2SO4 generates the sulphate ester of 2-hydroxyanthracene-9,10-dione in high yield along with the 1-hydroxy isomer and the novel reduction products anthracen-9(10H)-one and 9,9'-bianthracene-10,10'(9H,9'H)-dione; contrary to previous results, the product distribution and the rate of reaction are dependent upon the concentration of O2 in the solution.
- Broadbent, A. Douglas,Stewart, John M.
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p. 676 - 677
(2007/10/02)
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- Chemistry of Quinones. Part 6. The Selective Hydrolysis of α-Acetoxyanthraquinones and Related Compounds by Trifluoroacetic Acid Containing Small Amounts of Water
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Acetoxy- or benzoyloxy-substituents adjacent to the carbonyl groups of anthraquinone, 1,4-naphthoquinone, naphthacene-5,12-quinone, benzophenone, and methyl benzoate are selectively converted into hydroxy-groups by treatment with trifluoroacetic acid containing small amounts of water.In the absence of water a reversible acidolysis occurs.Water reacts with the acylating agent, thus preventing the reverse reaction.Evidence is presented that the hydrolyses are of the AAC1 type.
- Harrison, Charles R.,Hodge, Philip,Khan, Naeem
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p. 1592 - 1594
(2007/10/02)
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