Quinone Compounds Research Articles

Covalent bonding of aromatic amine daughter products of 2,4-dinitroanisole (DNAN) with model quinone compounds representing humus via nucleophilic addition.

2,4-Dinitroanisole (DNAN) is a component of insensitive munitions (IM), which are replacing traditional explosives due to their improved safety. Incomplete IM combustion releases DNAN onto the soil, where it can leach into the subsurface with rainwater, encounter anoxic conditions, and undergo (a)biotic reduction to aromatic amines 2-methoxy-5-nitroaniline (MENA), 4-methoxy-3-nitroaniline (iMENA, isomer of MENA), and 2,4-diaminoanisole (DAAN). We report here studies of nucleophilic addition mechanisms that may account for the sequestration of aromatic amine daughter products of DNAN into soil organic matter (humus), effectively removing these toxic compounds from the aqueous environment. Because quinones are important moieties in humus, we incubated MENA, iMENA, DAAN, and related analogs with model compounds 1,4-benzoquinone and 2,3-dimethyl-1,4-benzoquinone under anoxic conditions. Mass spectrometry and ultra-high performance liquid chromatography revealed that the aromatic amines had covalently bonded to either carbonyl carbons or ring carbons β to carbonyl carbons of the quinones, producing a mixture of imines and Michael adducts, respectively. These products formed rapidly and accumulated in the one-to four-day incubations. Nucleophilic addition reactions, which do not require catalysis or oxic conditions, are proposed as a mechanism resulting in the binding of DNAN to soil observed in previous studies. To remediate sites contaminated with DNAN or other nitroaromatics, reducing conditions and humus amendments may promote their immobilization into the soil matrix.

High−Performance organic lithium−ion battery with plastic crystal electrolyte

Organic quinone compounds are expected to become the main cathode materials for the next generation of energy storage devices due to their high capacity. However, they would soluble in conventional organic electrolytes, causing a reduction in electrochemical performance. Interestingly, the plastic crystal electrolyte (PCE) based on succinonitrile (SN) not only has high ionic conductivity, but also can alleviate the solubility problem of quinone compounds. In this study, the 5 mol% LiTFSI (lithium bis(trifluoromethane)sulfonimide)/SN PCE was firstly chosen to match with quinone compound calix[4]quinone (C4Q) to assemble lithium−ion batteries (LIBs). The SN−based electrolyte system greatly boosting batteries life and achieving good rate performance. With SN−based electrolyte, LIBs displayed an initial discharge specific capacity of 424 mAh g −1 (95% of theoretical specific capacity) at 0.1 C, and the capacity retention rate was still as high as 60% after 1000 cycles with the coulombic efficiency always around 100%. At 2 C, the capacity maintained around 140 mAh g −1 . Our work has great application value in LIBs due to the low cost and the excellent electrochemical performance of C4Q in LiTFSI/SN PCE. Succinonitrile (SN) plastic crystal electrolyte (PCE) has excellent electrical conductivity, and can effectively alleviate the dissolution problem of organic electrode materials in traditional electrolytes. The use of SN PCE greatly improves the cycle performance and rate capability of calix[4]quinone (C4Q) in lithium ion batteries.

Quinone perception in plants via leucine-rich-repeat receptor-like kinases.

Quinones are produced and sensed in all kingdoms of life1-4. Plants are primary producers of quinone1,2, but the role of quinone as a signalling agent in plants remains largely unknown. One well-documented role of quinone is in the induction of haustoria (specialized feeding structures) in plants that parasitize roots, which occurs in the presence of the host-derived quinone compound 2,6-dimethoxy-1,4-benzoquinone (DMBQ)5. However, how parasitic plants sense DMBQ remains unclear, as is whether nonparasitic plants are capable of sensing quinones. Here we use Arabidopsis thaliana and DMBQ as a model plant and quinone to show that DMBQ signalling occurs in Arabidopsis via elevation of cytosolic Ca2+ concentration. We performed a forward genetic screen in Arabidopsis that isolated DMBQ-unresponsive mutants, which we named cannot respond to DMBQ1 (card1). The CANNOT RESPOND TO DMBQ1 (CARD1; At5g49760, also known as HPCA1) gene encodes a leucine-rich-repeat receptor-like kinase that is highly conserved in land plants. In Arabidopsis, DMBQ triggers defence-related gene expression, and card1 mutants show impaired immunity against bacterial pathogens. In Phtheirospermum japonicum (a plant that parasitizes roots), DMBQ initiates Ca2+ signalling in the root and is important for the development of the haustorium. Furthermore, CARD1 homologues from this parasitic plant complement DMBQ-induced elevation of cytosolic Ca2+ concentration in the card1 mutant. Our results demonstrate that plants-unlike animals and bacteria-use leucine-rich-repeat receptor-like kinases for quinone signalling. This work provides insights into the role of quinone signalling and CARD1 functions in plants that help us to better understand the signalling pathways used during the formation of the haustorium in parasitic plants and in plant immunity in nonparasitic plants.

Residual Larvicidal Activity of Quinones against Aedes aegypti.

The number of documented dengue cases has increased dramatically in recent years due to transmission through the Aedes aegypti mosquito bite. Vector control remains the most effective measure to protect against this and other arboviral diseases including Zika, chikungunya and (urban) yellow fever, with an established vaccine only available for yellow fever. Although the quinone class shows potential as leading compounds for larvicide development, limited information restricts the development of optimized structures and/or formulations. Thus, in this contribution we investigated the larvicidal and pupicidal activity of three quinone compounds isolated from a Connarus suberosus root wood ethyl acetate extract together with 28 quinones from other sources. Eight quinones demonstrated larvicidal activity, of which tectoquinone (4) proved to be the most active (LC50 1.1 µg/mL). The essential residual effect parameter of four of these quinones was evaluated in laboratory trials, with tectoquinone (4) and 2-ethylanthraquinone (7) presenting the most prolonged activity. In small-scale field residual tests, tectoquinone (4) caused 100% larvae mortality over 5 days, supporting its selection for formulation trials to develop a prototype larvicide to control Ae. aegypti.

Metal Complexes of 5,15‐Porphyrinquinones: Systematic Study of Crystal Structure, Electronic Structure, and Lewis Acidity

We conducted the first systematic study on the synthesis, structure, and properties of various divalent metal complexes (NiII, CuII, ZnII, PdII, PtII, and PbII) of 5,15‐porphyrinquinone (PQ, a quinone compound of porphyrin) for diversifying the chemistry of traditional quinone‐metal complexes. Similar to electron‐accepting nature of PQ, the metal complexes studied here also exhibit it. NiII, PdII, and PtII complexes favor face‐to‐face stacked structures in the crystals, thus inducing effective PtII–PtII interaction, which has not been observed in the porphyrin analogues to date. Ultraviolet‐visible (UV/Vis) absorption spectra of the metal complexes vary widely depending on the metal ion and owing to the effective d(metal)–π(PQ) coupling in their molecular orbitals. Quantitative analyses of the axial ligation on the central metal ions (NiII and CuII) revealed significantly larger binding constants than those of the porphyrin analogues, indicating significant enhancement of their Lewis acidities due to the strong electron‐withdrawing nature of PQ.

Antifungal activity of hypocrellin compounds and their synergistic effects with antimicrobial agents against Candida albicans.

Summary Candida albicans is a common human fungal pathogen. The previous study revealed that quinone compounds showed antimicrobial activity against C. albicans by inhibiting cell growth. However, it was unclear whether quinones have other antifungal effects against C. albicans in addition to fungicidal effects. In this study, we assessed the inhibitory activity of a total of 25 quinone compounds against C. albicans morphological transition, which is essential for the pathogenicity of C. albicans. Several quinones exhibited strong inhibition of mycelium formation by C. albicans SC5314. Three leading compounds, namely hypocrellins A, B and C, also exhibited marked attenuation of C. albicans SC5314 virulence in both human cell lines and mouse infection models. These three compounds significantly suppressed the proliferation of C. albicans SC5314 cells in a mouse mucosal infection model. Intriguingly, hypocrellins not only attenuated the cytotoxicity of a nystatin‐resistant C. albicans strain but also showed excellent synergistic effects with antifungal agents against both wild‐type C. albicans SC5314 and the drug‐resistant mutant strains. In addition, hypocrellins A, B and C interfered with the biological functions and virulence of various clinical Candida species, suggesting the promising potential of these compounds for development as new therapeutic agents against infections caused by Candida pathogens.

Electrochemical redox behavior of organic quinone compounds in aqueous metal ion electrolytes

Organic quinone compounds are promising electrode materials for aqueous rocking-chair batteries due to chemical inert toward aqueous solutions and wide feasibility of various charge carriers. However, in aqueous electrolytes, the ion-pairing effect of different charge carriers on the electrochemical properties of organic quinone compounds remains unclear. Herein, we selecte a small molecule 9,10-anthraquinone as a study model and propose that the proton assisted metathesis reaction between anthrahydroquinone and M n+ results in stabilizing electrode reaction. Meantime, the possibility of anthraquinone as anode for aqueous multivalent metal-ion (Al 3+ , Mg 2+ , Zn 2+ ) batteries is illustrated. Typically for aluminum-ion battery, a reversible capacity of 211.4 mA h g -1 at 800 mA g -1 after 500 full cycles with a capacity retention of 94.5% can be obtained. This work may provide guidance to design and explore more organic quinone compounds for aqueous batteries. Here, two redox mechanisms of AQ in different aqueous metal ion electrolytes were proposed. In 1 M LiCl, NaCl, KCl, CaCl 2 and BaCl 2 , AQ molecule obtains an electron and becomes a radical anion [AQ] - , then a metal ion pairs with radical anion to form red [AQ-M n+ ] (n-1)+ ; In 1 M AlCl 3 , MgCl 2 and ZnCl 2 , AQ molecules undergoes one step two-electron redox process assisted by protons in electrolyte. Then metathesis reactions between AQ-H2 and metal-ions occur and induce morphology evolution in electrode. • Different electrochemical redox behaviors of AQ in different aqueous electrolytes were observed. • The spin density distribution of red species result in poor redox stability of AQ in 1M LiCl, NaCl, KCl, CaCl 2 and BaCl 2 . • Metathesis reactions assisted by protons induce the reversible redox reaction of AQ in 1 M AlCl 3 , MgCl 2 and ZnCl 2 . • The possibility of AQ as anode for aqueous multivalent metal-ion (Al 3+ , Mg 2+ , Zn 2+ ) batteries was demonstrated.

Recent Progress in Calix[n]quinone (n=4, 6) and Pillar[5]quinone Electrodes for Secondary Rechargeable Batteries

AbstractAttributing to the advantages of high theoretical specific capacity, good structural designability and environmental friendliness, organic quinone electrode materials have been applied in secondary batteries to achieve great electrochemical performances. At present, a series of researches about secondary batteries with quinone‐based compounds calix[4]quinone (C4Q), pillar[5]quinone (P5Q) and calix[6]quinone (C6Q) as cathodes have been carried out. In this review, we systematically summarize the applications of these three types of quinone compounds in lithium‐ion batteries (LIBs), sodium‐ion batteries (SIBs), zinc‐ion batteries (ZIBs), and magnesium‐ion batteries (Mg‐ion batteries). The optimizing methods for suppressing the dissolution of organic electrode materials such as quasi‐solid‐state electrolytes, all‐solid‐state electrolytes, ionic liquid electrolytes, aqueous electrolytes and carbon immobilization are concluded. This review could provide a good guideline to improve the electrochemical performances of secondary batteries using quinone compounds as cathodes in the future.

Combination of high performance organic cathode Calix[4]quinone and practical biocarbon in sodium-ion batteries

Abstract Nowadays, sodium-ion batteries (SIBs) have received extensive attention for their abundant resources and low price. Some quinone compounds have the advantages of high specific capacity, diverse structures, environmental friendliness and good redox reversibility, are ideal cathode materials. Calix[4]quinone (C4Q) with a high theoretical specific capacity of 446 mA h g−1 is synthesized as cathodes, while it is still puzzled over low conductivity and high dissolution rate in organic electrolytes. In this study, a kind of economical and practical biocarbon-PPL with porous tubular structures is prepared by pyrolysis of Physalis Peruviana L. Calyx to immobilize C4Q in SIBs for the first time. The C4Q/PPL cathode presents an initial capacity of 435 mA h g−1 with stable cyclability (195 mA h g−1 after 100 cycles at 0.1 C) and great rate performance (170 mA h g−1 at 1 C).

Redox-Active Phenanthrenequinone Triangles in Aqueous Rechargeable Zinc Batteries.

Aqueous rechargeable zinc batteries (ZBs) have received considerable attention recently for large-scale energy storage systems in terms of rate performance, cost, and safety. Nevertheless, these ZBs still remain a subject for investigation, as researchers search for cathode materials enabling high performance. Among the various candidate cathode materials for ZBs, quinone compounds stand out as candidates because of their high specific capacity, sustainability, and low cost. Quinone-based cathodes, however, suffer from the critical limitation of undergoing dissolution during battery cycling, leading to a deterioration in battery life. To address this problem, we have introduced a redox-active triangular phenanthrenequinone-based macrocycle (PQ-Δ) with a rigid geometry and layered superstructure. Notably, we have confirmed that Zn2+ ions, together with H2O molecules, can be inserted into the PQ-Δ organic cathode, and, as a consequence, the interfacial resistance between the cathode and electrolytes is decreased effectively. Density functional theory calculations have revealed that the low interfacial resistance can be attributed mainly to decreasing the desolvation energy penalty as a result of the insertion of hydrated Zn2+ ions in the PQ-Δ cathode. The combined effects of the insertion of hydrated Zn2+ ions and the robust triangular structure of PQ-Δ serve to achieve a large reversible capacity of 210 mAh g-1 at a high current density of 150 mA g-1, along with an excellent cycle-life, that is, 99.9% retention after 500 cycles. These findings suggest that the utilization of electron-active organic macrocycles, combined with the low interfacial resistance associated with the solvation of divalent carrier ions, is essential for the overall performance of divalent battery systems.

Characterization of bioactive and bioenergy components from fresh walnut (Juglans regia) leaf

Walnut (Juglans regia) is an important economic tree specie, and has unique aroma in its leaf. In order to investigate the bioactive and bioenergy characteristic of compounds in ethanol and benzene extracts from fresh walnut leaf by gas chromatography/mass spectrometry (GC-MS). The results indicated that ethanol and benzene extracst fresh walnut leaf contain abundant alcohols, aromatic hydrocarbons, quinones, phenols, aldehydes, acids, ketones, alkanes, esterscompounds, especially including dl-.alpha.-Tocopherol, juglone, squalene andlupeol, which are important bioactive components. The functional analytic result suggested that compounds from fresh walnut leaf extracts can be developed into raw materials for industries of biofuel, biomedicine, cosmetic, spices and food additive. The ethanol extract of fresh walnut leaf is more rich in biomedicine and food additives components, such as ketones, alkanes, aldehydes, amines, and acides compounds. The benzene extract of fresh walnut leaf is more rich in biofuels, spices, and cosmetic components, such as phenols, aromatic hydrocarbons, olefines and quinones compounds.

Cryptotanshinone enhances wound healing in type 2 diabetes with modulatory effects on inflammation, angiogenesis and extracellular matrix remodelling

Context Cryptotanshinone (CT) is a diterpene quinone compound from Salvia miltiorrhiza Bge. Labiatae has been widely used in cardio-cerebral vascular diseases, which could be potentially effective in treating diabetic wounds. Objective This study evaluates the wound healing activity of CT by employing an excisional wound splinting model in db/db mice. Materials and methods Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with sodium carboxymethyl cellulose (CMC-Na) or 300 mg/kg/d CT for 16 days. Wound closure was measured every two days. Body weight, fasting blood glucose, re-epithelialization, granulation, leukocyte infiltration, capillary density, collagen deposition and expressions of CXCL1, CXCL2, VEGF, Ang-1, p-eNOS, eNOS, α-SMA, MMP2 and MMP9 were analysed. Expression of VEGF and tube formation was measured in vitro with human umbilical vein endothelial cells (HUVECs). Results CT significantly accelerated rate of wound closure, as the contraction ratio increased from 68% (non-treated group) to 83% (CT-treated group) at days 16 post-injury. A significant increase was observed in re-epithelialization and granulation tissue formation. Mechanistically, CT suppressed leukocyte infiltration and CXCL1 and CXCL2 expression. CT treatment also increased blood vessel density and expression level of VEGF, Ang-1 and p-eNOS. In vitro, CT boosted expression of VEGF and tube formation of endothelial cells. Moreover, extracellular matrix (ECM) remodelling was enhanced by CT via promoting fibroblast transformation and inhibiting MMP2 and MMP9. Conclusions Our study provides evidence that CT could be developed as a potential therapeutic agent for the treatment of chronic diabetic wound healing.

Modification of Cys residues in human thioredoxin-1 by p-benzoquinone causes inhibition of its catalytic activity and activation of the ASK1/p38-MAPK signalling pathway

Quinones can modify biological molecules through both redox-cycling reactions that yield radicals (semiquinone, superoxide and hydroxyl) and via covalent adduction to nucleophiles (e.g. thiols and amines). Kinetic data indicate that Cys residues in GSH and proteins are major targets. In the studies reported here, the interactions of a prototypic quinone compound, p-benzoquinone (BQ), with the key redox protein, thioredoxin-1 (Trx1) were examined. BQ binds covalently with isolated Trx1 forming quinoprotein adducts, resulting in a concentration-dependent loss of enzyme activity and crosslink formation. Mass spectrometry peptide mass mapping data indicate that BQ forms adducts with all of the Trx1 Cys residues. Glutathione (GSH) reacts competitively with BQ, and thereby modulates the loss of activity and crosslink formation. Exposure of macrophage-like (J774A.1) cells to BQ results in a dose-dependent loss of Trx and thioredoxin reductase (TrxR) activities, quinoprotein formation, and a decrease in GSH levels without a concomitant increase in oxidized glutathione. GSH depletion aggravates the loss of Trx and TrxR activity. These data are consistent with adduction of GSH to BQ being a primary protective pathway. Reaction of BQ with Trx in cells resulted in the activation of apoptosis signal-regulating kinase 1 (ASK1), and p38 mitogen-activated protein kinase (MAPK) leading to apoptotic cell death. These data suggest that BQ reacts covalently with Cys residues in Trx, including at the active site, leading to enzyme inactivation and protein cross-linking. Modification of the Cys residues in Trx also results in activation of the ASK1/p38-MAPK signalling pathway and promotion of apoptotic cell death.

Calix[6]quinone as high-performance cathode for lithium-ion battery

Organic quinone compounds have attracted wide attention due to their high theoretical capacities. Here, a novel cyclic macromolecular calix[6]quinone (C6Q), which possesses 6 p -quinone units and can provide 12 electrochemical active sites, has been applied as a promising cathode material in lithium ion batteries (LIBs). The as-fabricated LIBs exhibited an initial specific capacity as high as 423 mA h g−1 ( C theo = 447 mA h g−1 ) at 0.1 C . After 100 cycles, the capacity of C6Q maintained at 216 mA h g−1 , and even after 300 cycles, C6Q still achieved a high specific capacity of 195 mA h g−1 with negligible capacity fading (as compared with the 100th cycle). Due to the large capacity and wide electrochemical window, C6Q can deliver a specific energy up to 1201 W h kg−1 . In addition, the method of immobilizing C6Q with ordered mesoporous carbon (OMC) CMK-3 could further enhance the electrochemical performance of C6Q.

The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance in Staphylococcus aureus.

Aims: Quinone compounds are electron carriers and have antimicrobial and toxic properties due to their mode of actions as electrophiles and oxidants. However, the regulatory mechanism of quinone resistance is less well understood in the pathogen Staphylococcus aureus.Results: Methylhydroquinone (MHQ) caused a thiol-specific oxidative and electrophile stress response in the S. aureus transcriptome as revealed by the induction of the PerR, QsrR, CstR, CtsR, and HrcA regulons. The SACOL2531-29 operon was most strongly upregulated by MHQ and was renamed as mhqRED operon based on its homology to the Bacillus subtilis locus. Here, we characterized the MarR-type regulator MhqR (SACOL2531) as quinone-sensing repressor of the mhqRED operon, which confers quinone and antimicrobial resistance in S. aureus. The mhqRED operon responds specifically to MHQ and less pronounced to pyocyanin and ciprofloxacin, but not to reactive oxygen species (ROS), hypochlorous acid, or aldehydes. The MhqR repressor binds specifically to a 9–9 bp inverted repeat (MhqR operator) upstream of the mhqRED operon and is inactivated by MHQ in vitro, which does not involve a thiol-based mechanism. In phenotypic assays, the mhqR deletion mutant was resistant to MHQ and quinone-like antimicrobial compounds, including pyocyanin, ciprofloxacin, norfloxacin, and rifampicin. In addition, the mhqR mutant was sensitive to sublethal ROS and 24 h post-macrophage infections but acquired an improved survival under lethal ROS stress and after long-term infections.Innovation: Our results provide a link between quinone and antimicrobial resistance via the MhqR regulon of S. aureus.Conclusion: The MhqR regulon was identified as a novel resistance mechanism towards quinone-like antimicrobials and contributes to virulence of S. aureus under long-term infections.

Inhibition and crosslinking of the selenoprotein thioredoxin reductase-1 by p-benzoquinone

Quinones are common in nature, and often cytotoxic. Their proposed toxicity mechanisms involve redox cycling with radical generation, and/or reactions with nucleophiles, such as protein cysteine (Cys) residues, forming adducts via Michael addition reactions. The selenenyl anion of selenocysteine (Sec) is a stronger nucleophile, more prevalent at physiological pH, and more reactive than the corresponding thiolate anion of Cys. We therefore hypothesized that Sec residues should be readily modified by quinones and with potential consequences for the structure and function of selenoproteins. Here, we report data on the interaction of p-benzoquinone (BQ) with the selenoprotein thioredoxin reductase-1 (TrxR1), which exposes an accessible Sec residue upon physiological reduction by NADPH. Our results reveal that BQ targets NADPH-reduced TrxR1 and inhibits its activity using 5,5′-dithiobis(2-nitrobenzoic acid) or juglone as model substrates, consistent with the targeting of both the Cys and Sec residues of TrxR1. In the absence of NADPH, BQ modified the non-catalytic Cys residues, leading to subunit crosslinking, mainly through disulfides, which also resulted in some loss of activity. This crosslinking was time-dependent and independent of the Sec residue. Addition of NADPH after BQ pre-treatment could resolve the disulfide-linked crosslinking. TrxR activity loss was also observed upon incubation of J774A.1 cells or cell lysates with BQ. These data suggest that BQ readily targets TrxR1, albeit in a rather complex manner, which results in structural changes and loss of enzyme activity. We suggest that TrxR1 targeting can explain some of the cytotoxicity of BQ, and potentially also that of other quinone compounds.

Dicyanobenzoquinone Functionalized Carbon Nanotubes As Cathode Materials for Rechargeable Lithium and Sodium Ion Batteries

Currently, lithium ion batteries (LIBs) and sodium ion batteries (SIBs) mainly depend on inorganic cathode materials, which are still plagued by several issues restricting their advancement such as power density, sustainability, and safety. As alternatives, organic electrode materials have been intensively investigated for both LIBs and SIBs due to their advantages of sustainability, flexibility of structure design and environmental friendliness. Among them, organic quinone materials offer a sustainable approach for electric energy storage, however, their intrinsic electrical insulation and dissolution into the electrolyte during cycling have hampered their wide application. To tackle these two issues, we have synthesized novel organic cathode materials by anchoring a quinone compound, 2,3-dicyano-p-benzoquinone (DCBQ) with a high redox potential of 3.37 V vs. Li/Li+, onto carbon nanotubes (CNTs) (CNTs-DCBQ) through a facile ‘‘grafting to’’ method. The elaborate combination of excellent electron conductivity and large surface area of CNTs and stable and reversible redox reaction of DCBQ enables CNTs-DCBQ delivering high reversible capacities of 206.9 and 175.8 mA h g-1 at a current density of 10 mA g-1 and also remarkable capacities of 110.2 and 82.1 mA h g-1 at a higher current density of 200 mA g-1 with a capacity retention approaching 100 % after 1000 cycles for lithium and sodium ion batteries, respectively.

A novel 1,4-naphthoquinone-derived compound induces apoptotic cell death in breast cancer cells.

Breast cancer is the most-diagnosed cancer type among women. The triple-negative subtype is an especially aggressive type of breast cancer. Although chemotherapy is almost the only option for the treatment of triple-negative breast cancer (TNBC), currently used chemotherapeutics are not effective enough, considering the poor survival rate of patients. Therefore, novel compounds need to be developed to improve survival rates. It has been known that quinonic compounds, which are found in nature, have antibacterial, antifungal, and antitumorigenic properties. Naphthoquinones are members of the quinone family and are widely used in research due to their promising properties. In this study, we evaluated the cytotoxic activity of a novel naphthoquinone-derived compound (1,4-naphthoquinone (1,4-NQ)) against two different breast cancer cells: a hormone-responsive cell line (MCF-7) and a triple-negative cell line (MDA-MB-231). As a result, 1,4-NQ decreased cell viability in both tested cell lines in a dose-dependent manner. Increased apoptotic markers (presence of pyknotic nuclei, annexin-V positivity, caspase 3/7 activity, and decreased mitochondrial membrane potential) and DNA damage were especially observed in MDA-MB-231 cells after treatment with the compound. Considering the promising cytotoxic effect of the compound, 1,4-NQ needs further evaluation as a potential candidate for the treatment of TNBC.

Protein kinase A activation by β‑Lapachone is associated with apoptotic cell death in NQO1‑overexpressing breast cancer cells.

One million females are diagnosed worldwide every year with breast cancer, and the mortality rate of these patients remains high. Several treatments, including surgery, are available for breast cancer. β‑Lapachone (β‑Lap), a natural quinone compound, has been developed for cancer treatment due to its strong cytotoxic effect through its action on NAD(P)H:quinone oxidoreductase1(NQO1)‑dependent activity. However, the mechanism in regards to how β‑Lap induces cytotoxicity in breast cancer cells is still elusive. In the present study, we showed that β‑Lap induced apoptotic cell death via activation of protein kinaseA (PKA) in NQO1‑overexpressing MDA‑MB‑231 human breast cancer cells. This PKA‑dependent cell death was observed solely in NQO1‑overexpressing 231 cells via the high production of reactive oxygen species (ROS). Cell survival of antioxidant [N‑acetylcysteine (NAC)]‑treated NQO1‑overexpressing 231 cells was significantly recovered, and NQO1‑negative 231 cells did not respond to β‑Lap. Antiapoptotic proteins such as Bcl2 and Bcl‑xL were decreased, while proapoptotic proteins, including cytochrome c, activation of caspase‑3, and cleavage of PARP were increased after β‑Lap treatment of NQO1‑overexpressing231 cells. Furthermore, PKA activators, forskolin or dibutyryl‑cAMP, an analog of cAMP, aggravated the β‑Lap‑induced apoptotic cell death by decreasing antiapoptotic proteins and further activating proapoptotic proteins in NQO1‑positive 231 cells. Treatment with a PKA inhibiter, H89, significantly increased cell viability even in NQO1‑overexpressing cells treated with β‑Lap. These data showed that β‑Lap activated PKA via ROS accumulation, subsequently leading to apoptotic cell death in NQO1‑positive breast cancer cells.

The toxicological analysis of secondary organic aerosol in human lung epithelial cells and macrophages.

Secondary organic aerosol (SOA) is a component of airborne particulate matter in urban areas. However, their toxicities remain incompletely understood. In this study, we investigated the oxidative and inflammatory potency of SOA derived from three different volatile organic compounds (α-pinene, m-xylene, and trimethylbenzene) using human bronchial epithelial cells (BEAS-2B) and macrophages (U937). In BEAS-2B cells, all types of SOA extracts increased the expression of the heme oxygenase 1 (HMOX1) and interleukin-8 (IL8) genes, a typical marker for oxidative stress and inflammatory responses, respectively. Among the three types of SOA, m-xylene-derived SOA showed the strongest induction of the HMOX1 and IL8 genes, and transcriptional activity via the antioxidant response element (ARE). A causal candidate for SOA induction of oxidative stress is 2,6-dimethyl-1,4-benzoquinone (DMBQ) because only this quinone compound increased the transcriptional activity via ARE among components tested in this study. Similar to the case of BEAS-2B cells, SOA extracts increased the expression of HMOX1 and IL8 genes in U937 cells, mainly through oxidative stress, but these responses in U937 cells were prolonged when compared with BEAS-2B cells. Together, these results show that SOA affects lung epithelial cells and macrophages mainly through oxidative stress and inflammation, suggesting their contribution to the development of respiratory diseases.