1,4-Anthraquinone

Novel O-propyl, S-propyl, and N-propyl substituted 1,4-naphthoquinones and 1,4-anthraquinones as potential fingermark development reagents for porous surfaces.[Pubmed:33090521]

J Forensic Sci. 2020 Oct 14.

Lawsone is a 2-substituted-1,4-naphthoquinone derivative, which has been proposed as an alternative to the reagents currently used for fingermark detection on porous surfaces. 2-substituted-anthraquinones, which contain an additional conjugated benzene ring, have a similar chemical structure to that of lawsone. In this study, a new series of 2-substituted-1,4-naphthoquinones and 2-substituted-1,4-Anthraquinones were synthesized and completely characterized by(1)H NMR,(13)C NMR, IR, and HPLC-TOF/MS analyses. All newly synthesized 2-substituted-1,4-quinones were investigated for their ability to develop latent fingermarks on porous surfaces, and this ability was compared with that of lawsone. Each fingermark developed was graded using an established method; thus, quantitative data were attributed to each fingermark. It has been demonstrated that the 1,4-quinones react with amino acids present in latent fingermarks on selected paper surfaces to produce faint yellow-orange impressions, which exhibit strong photoluminescence when illuminated with a forensic light source at 440 nm and observed through a red filter. None of the compounds caused background darkening. The results obtained were generally similar to those of lawsone, however, 8-dibromo-2-(propylamino)naphthalene-1,4-dione and 5,8-dibromo-2-(propylthio)naphthalene-1,4-dione yielded better results for copier paper and colored (blue) copier paper used in this analysis. To the best of our knowledge, this is the first study to examine the role of 1,4-Anthraquinone derivatives as potential fingermark development reagents. The results indicate that 1,4-quinones have a potential to be used as reagents for enhancement of latent fingermarks.

Concise Synthesis of 1,4-Benzoquinone-Based Natural Products as Mitochondrial Complex I Substrates and Substrate-Based Inhibitors.[Pubmed:32730688]

ChemMedChem. 2020 Jul 30.

A short, efficient one-step synthesis of 2-methyl-5-(3-methyl-2-butenyl)-1,4-benzoquinone, a natural product from Pyrola media is described. The synthesis is based on a direct late C-H functionalization of the quinone scaffold. The formation of the natural product was confirmed by means of 2D-NMR spectroscopy. Additional derivatives were synthesized and tested alongside the natural product as potential substrate and substrate-based inhibitors of mitochondrial complex I (MCI). The structure-activity relationship study led to the discovery of 3-methylbuteneoxide-1,4-Anthraquinone (1 i), an inhibitor with an IC50 of 5 muM against MCI. The identified molecule showed high selectivity for MCI when tested against other quinone-converting enzymes, including succinate dehydrogenase, and the Na (+)-translocating NADH:quinone oxidoreductase. Moreover, the identified inhibitor was also active in cell-based proliferation assays. Therefore, 1 i can be considered as a novel chemical probe for MCI.

Antileishmanial activity of terpenylquinones on Leishmania infantum and their effects on Leishmania topoisomerase IB.[Pubmed:31678841]

Int J Parasitol Drugs Drug Resist. 2019 Dec;11:70-79.

Leishmania is the aethiological agent responsible for the visceral leishmaniasis, a serious parasite-borne disease widely spread all over the World. The emergence of resistant strains makes classical treatments less effective; therefore, new and better drugs are necessary. Naphthoquinones are interesting compounds for which many pharmacological properties have been described, including leishmanicidal activity. This work shows the antileishmanial effect of two series of terpenyl-1,4-naphthoquinones (NQ) and 1,4-Anthraquinones (AQ) obtained from natural terpenoids, such as myrcene and myrceocommunic acid. They were evaluated both in vitro and ex vivo against the transgenic iRFP-Leishmania infantum strain and also tested on liver HepG2 cells to determine their selectivity indexes. The results indicated that NQ derivatives showed better antileishmanial activity than AQ analogues, and among them, compounds with a diacetylated hydroquinone moiety provided better results than their corresponding quinones. Regarding the terpenic precursor, compounds obtained from the monoterpenoid myrcene displayed good antiparasitic efficiency and low cytotoxicity for mammalian cells, whereas those derived from the diterpenoid showed better antileishmanial activity without selectivity. In order to explore their mechanism of action, all the compounds have been tested as potential inhibitors of Leishmania type IB DNA topoisomerases, but only some compounds that displayed the quinone ring were able to inhibit the recombinant enzyme in vitro. This fact together with the docking studies performed on LTopIB suggested the existence of another mechanism of action, alternative or complementary to LTopIB inhibition. In silico druglikeness and ADME evaluation of the best leishmanicidal compounds has shown good predictable druggability.

Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone.[Pubmed:30986933]

Molecules. 2019 Apr 2;24(7). pii: molecules24071279.

Quinones are secondary metabolites of higher plants associated with many biological activities, including antiviral effects and cytotoxicity. In this study, the anti-herpetic and anti-dengue evaluation of 27 terpenyl-1,4-naphthoquinone (NQ), 1,4-Anthraquinone (AQ) and heterocycle-fused quinone (HetQ) derivatives was done in vitro against Human Herpesvirus (HHV) type 1 and 2, and Dengue virus serotype 2 (DENV-2). The cytotoxicity on HeLa and Jurkat tumor cell lines was also tested. Using plaque forming unit assays, cell viability assays and molecular docking, we found that NQ 4 was the best antiviral compound, while AQ 11 was the most active and selective molecule on the tested tumor cells. NQ 4 showed a fair antiviral activity against Herpesviruses (EC50: <0.4 microg/mL, <1.28 microM) and DENV-2 (1.6 microg/mL, 5.1 microM) on pre-infective stages. Additionally, NQ 4 disrupted the viral attachment of HHV-1 to Vero cells (EC50: 0.12 microg/mL, 0.38 microM) with a very high selectivity index (SI = 1728). The in silico analysis predicted that this quinone could bind to the prefusion form of the E glycoprotein of DENV-2. These findings demonstrate that NQ 4 is a potent and highly selective antiviral compound, while suggesting its ability to prevent Herpes and Dengue infections. Additionally, AQ 11 can be considered of interest as a leader for the design of new anticancer agents.

First thia-Diels-Alder reactions of thiochalcones with 1,4-quinones.[Pubmed:30112087]

Beilstein J Org Chem. 2018 Jul 19;14:1834-1839.

Aryl and hetaryl thiochalcones react smoothly with 1,4-quinones in THF solution at 60 degrees C yielding the corresponding fused 4H-thiopyrans after spontaneous dehydrogenation of the initially formed [4 + 2] cycloadducts. In general, the yields of the isolated products were high. With 5-chloro-10-hydroxy-1,4-Anthraquinone, the thia-Diels-Alder reaction occurred with complete regioselectivity. In the case of the reaction of vitamin K3 (menadione) with diphenylthiochalcone, the initial cycloadduct was isolated in 37% yield.

1,4-Anthraquinone: A new useful pre-column reagent for the determination of N-acetylcysteine and captopril in pharmaceuticals by high performance liquid chromatography.[Pubmed:28633061]

J Pharm Biomed Anal. 2017 Sep 5;143:299-304.

1,4-Anthraquinone (ANQ) is proposed as a novel pre-column reagent for high performance liquid chromatography (HPLC) determination of N-acetylcysteine (NAC) and captopril (CAP) in pharmaceutical formulations. The derivatization reactions were carried out at room temperature: NAC at pH 8 for 1min, while CAP at pH 7.5 for 20min. Both reactions reached completeness at a reagent to thiol molar ratio of about 2.5. The synthesised derivatives were characterized by (1)H NMR and IR. The chromatographic separations were performed on a C18 Phenomenex Synergi Fusion 4mum (250mmx4.6mm I.D.) stainless steel column with detection at lambda=300nm. The mobile phase consisted of methanol/triethylammonium (TEA) phosphate buffer (pH 3; 0.05mol/L) 75:25 (v/v) at a flow-rate of 0.4mL/min for NAC and 88:12 (v/v), at a flow-rate of 0.6mL/min for CAP. The validation parameters (linearity, sensitivity, accuracy, precision, specificity and stability) were highly satisfactory. Linear response was observed (determination coefficient >/=0.9996). Detection limits were about 8 and 18ng/mL for NAC and CAP, respectively. Intra-day precision (relative standard deviation, R.S.D.) was

Design and synthesis of propellane derivatives and oxa-bowls via ring-rearrangement metathesis as a key step.[Pubmed:26664592]

Beilstein J Org Chem. 2015 Sep 24;11:1727-31.

Various intricate propellane derivatives and oxa-bowls have been synthesized via a ring-rearrangement metathesis (RRM) as a key step starting from readily accessible starting materials such as p-benzoquinone, 1,4-naphthoquinone and 1,4-Anthraquinone.

9,10-Dihydrophenanthrene derivatives and one 1,4-anthraquinone firstly isolated from Dioscorea zingiberensis C. H. Wright and their biological activities.[Pubmed:26656408]

Fitoterapia. 2016 Mar;109:20-4.

Two new phenanthrene derivatives, 2,5,7-trimethoxy-9,10-dihydrophenanthrene-1,4-dione (1) and 2,5,6-trihydroxy-3,4-dimethoxy-9,10-dihydrophenanthrene (3), one new anthracenedione, 2,5,7-trimethoxyanthracene-1,4-dione (2), together with two known 9,10-dihydrophenanthrenes (4-5) were isolated from the rhizomes of Dioscorea zingiberensis C. H. Wright. The structures of these new compounds were established based on extensive NMR spectroscopy. Several isolated compounds were evaluated for the inhibition against nitric oxide (NO) production in the lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cell line, DPPH radical scavenging, and inhibitory activity on Free Fatty Acids (FFAs) induced triglyceride accumulation in HepG2 cells. Compound 2 exhibited moderate anti-inflammatory activity, compound 3 possessed comparable DPPH radical scavenging activity as Vitamin C, compounds 2 and 4 showed potent inhibitory activities on triglyceride accumulation.

Polyanthraquinone as a Reliable Organic Electrode for Stable and Fast Lithium Storage.[Pubmed:26411505]

Angew Chem Int Ed Engl. 2015 Nov 16;54(47):13947-51.

In spite of recent progress, there is still a lack of reliable organic electrodes for Li storage with high comprehensive performance, especially in terms of long-term cycling stability. Herein, we report an ideal polymer electrode based on anthraquinone, namely, polyanthraquinone (PAQ), or specifically, poly(1,4-Anthraquinone) (P14AQ) and poly(1,5-anthraquinone) (P15AQ). As a lithium-storage cathode, P14AQ showed exceptional performance, including reversible capacity almost equal to the theoretical value (260 mA h g(-1); >257 mA h g(-1) for AQ), a very small voltage gap between the charge and discharge curves (2.18-2.14=0.04 V), stable cycling performance (99.4% capacity retention after 1000 cycles), and fast-discharge/charge ability (release of 69% of the low-rate capacity or 64% of the energy in just 2 min). Exploration of the structure-performance relationship between P14AQ and related materials also provided us with deeper understanding for the design of organic electrodes.

2-Phenoxy-1,4-naphthoquinones: From a Multitarget Antitrypanosomal to a Potential Antitumor Profile.[Pubmed:26237241]

J Med Chem. 2015 Aug 27;58(16):6422-34.

A small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-Anthraquinone derivatives was initially developed to optimize the antitrypanosomatid profile of the multitarget hit compound B6 (1). The whole series was evaluated against the three most important human trypanosomatid pathogens (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani), and two compounds (14 and 21) showed good activity, despite a concomitant mammalian cytotoxicity. Furthermore, a subset also inhibited the glycolytic TbGAPDH enzyme in vitro. In light of these results and aware of the antitumor properties of quinones, the anticancer potential of some selected derivatives was investigated. Intriguingly, the tested compounds displayed antitumor activity, while being less toxic against noncancerous cells. The observed cytotoxic potency was ascribed to a multitarget mechanism of action accounting for hGAPDH inhibition and mitochondrial toxicity. Overall, the development of further derivatives, able to finely modulate multiple pathways of cancer or parasite cell metabolism, might lead to more effective treatments against these devastating diseases.

Reactive paper spray mass spectrometry for in situ identification of quinones.[Pubmed:25462369]

Rapid Commun Mass Spectrom. 2015 Jan 15;29(1):100-6.

RATIONALE: The polycyclic aromatic hydrocarbons quinones are reported to be harmful and could cause mutations and cancer via the generation of reactive oxygen species through their redox cycle in human body. For detection by gas chromatography and high-performance liquid chromatography mass spectrometry (MS), sample pretreatments and chromatographic separation prior to MS are generally required, which makes the whole analytical process laborious and time-consuming, resulting in difficulties for fast screening targets from complicated matrices. Thus facile, rapid and reliable MS methods for detection of quinones in complicated matrices are in great demand. METHODS: Reactive paper spray mass spectrometry is reported for rapid identification and quantification of quinones in complicated matrices. The method is based on an in situ derivatization reaction between cysteamine and quinones prior to analysis with paper spray mass spectrometry. With the addition of an easily charged chemical tag, the ionization efficiency of analysts is greatly improved. Due to the high ionization efficiency of the drivatives, quinones in complicated matrices could be detected rapidly without any pretreatment. RESULTS: Under the optimized experimental conditions, the linear dynamic ranges for both 1,4-benzoquinone and 1,4-naphthoquinone are 0.4-40 ng and that for 1,4-Anthraquinone is 0.4-20 ng. Limits of detection for these three analytes were measured to be 160, 40 and 200 pg using methyl-p-benzoquinone as internal standard. The capability to conduct MS analysis under ambient pressure is illustrated by identification of 1,4-naphthoquinone and 1,4-Anthraquinone in raw urine, raw serum and cell culture medium. CONCLUSIONS: Reactive paper spray could be applied to fast screening of quinones from complicated matrices. Therefore, we believe that reactive paper spray mass spectrometry might be potentially useful in the fields of environmental sciences, metabolomics and clinic analysis.

Chemoenzymatic synthesis of novel C-ribosylated naphthoquinones.[Pubmed:24015959]

ACS Chem Biol. 2013 Nov 15;8(11):2377-82.

The biological activity of many natural products is dependent on the presence of carbohydrate units, which are usually attached via an O-glycosidic linkage by glycosyltransferases. Recently, an exceptional C-ribosylation event was discovered in the biosynthesis of the polyketide antibiotic alnumycin A. The two-step process involves initial attachment of d-ribose-5-phosphate to the polyaromatic aglycone by the C-glycosynthase AlnA and subsequent dephosphorylation by AlnB, an enzyme of the haloacid dehalogenase family. Here, we tested 23 unnatural substrates to probe the C-ribosylation reaction. The chemoenzymatic synthesis of C-ribosylated juglone, 7-methyl juglone, monomethyl naphthazarin, 8-chloro-7-methyl juglone, and 9-hydroxy-1,4-Anthraquinone revealed the importance of a 1,4-quinoid system with an adjacent phenolic ring in order for reaction to occur. To further rationalize the molecular basis for reactivity, factors governing substrate recognition were investigated by NMR binding experiments. Additionally, the suitability of substrates for nucleophilic substitution was assessed by molecular modeling using density functional theory (DFT) calculations.

Ex(2)Box: interdependent modes of binding in a two-nanometer-long synthetic receptor.[Pubmed:23865381]

J Am Chem Soc. 2013 Aug 28;135(34):12736-46.

Incorporation of two biphenylene-bridged 4,4'-bipyridinium extended viologen units into a para-phenylene-based cyclophane results in a synthetic receptor that is ~2 nm long and adopts a box-like geometry. This cyclophane, Ex(2)Box(4+), possesses the ability to form binary and ternary complexes with a myriad of guest molecules ranging from long pi-electron-rich polycyclic aromatic hydrocarbons, such as tetracene, tetraphene, and chrysene, to pi-electron-poor 2,6-dinitrotoluene, 1,2,4-trichlorobenzene, and both the 9,10- and 1,4-Anthraquinone molecules. Moreover, Ex(2)Box(4+) is capable of forming one-to-one complexes with polyether macrocycles that consist of two pi-electron-rich dioxynaphthalene units, namely, 1,5-dinaphtho[38]crown-10. This type of broad molecular recognition is possible because the electronic constitution of Ex(2)Box(4+) is such that the pyridinium rings located at the "ends" of the cyclophane are electron-poor and prefer to enter into donor-acceptor interactions with pi-electron-rich guests, while the "middle" of the cyclophane, consisting of the biphenylene spacer, is more electron-rich and can interact with pi-electron-poor guests. In some cases, these different modes of binding can act in concert to generate one-to-one complexes which possess high stability constants in organic media. The binding affinity of Ex(2)Box(4+) was investigated in the solid state by way of single-crystal X-ray diffraction and in solution by using UV-vis and NMR spectroscopy for 12 inclusion complexes consisting of the tetracationic cyclophane and the corresponding guests of different sizes, shapes, and electronic compositions. Additionally, density functional theory was carried out to elucidate the relative energetic differences between the different modes of binding of Ex(2)Box(4+) with anthracene, 9,10-anthraquinone, and 1,4-Anthraquinone in order to understand the degree with which each mode of binding contributes to the overall encapsulation of each guest.