Quinone-enhanced Ascorbate Reduction of Nitric Oxide: Role of Quinone Redox Potential

The quinones 1,4-naphthoquinone (NQ), methyl-1,4-naphthoquinone (MNQ), trimethyl-1,4-benzoquinone (TMQ) and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UQ-0) enhance the rate of nitric oxide (NO) reduction by ascorbate in nitrogen-saturated phosphate buffer (pH 7.4). The observed rate constants for this reaction were determined to be 16±2,215±6,290±14 and 462±18?M^-1?s^-1, for MNQ, TMQ, NQ and UQ-0, respectively. These rate constants increase with an increase in quinone one-electron redox potential at neutral pH, E₇₁. Since NO production is enhanced under hypoxia and under certain pathological conditions, the observations obtained in this work are very relevant to such conditions.     

Aminonaphthoquinone induces oxidative stress in Staphylococcus aureus.

The biological activity of 5-amino-8-hydroxy-1,4-naphthoquinone (ANQ) on Staphylococcus aureus was investigated in comparison with the unsubstituted 1,4-naphthoquinone (NQ). Complete inhibition of microbial growth was observed with ANQ and NQ at 50 and 10 microg/mL, respectively. The antibacterial effect of naphthoquinones decreased in the presence of sodium ascorbate, but the superoxide scavenger 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron) was able to protect S. aureus only from the harmful effect of ANQ. Naphthoquinones blocked oxygen uptake and induced cyanide-insensitive oxygen consumption. When combining rotenone or salicylhydroxamic acid with ANQ or NQ, a slight decrease in respiratory activity was observed. Assays in the presence of naphthoquinones induced an increase of lipid peroxidation in S. aureus, as determined by thiobarbituric acid reactive substances. These results showed that 1,4-naphthoquinones effectively act as electron acceptors and induce an increase in reactive oxygen species that are toxic to S. aureus cells.     

Quinone-enhanced ascorbate reduction of nitric oxide: role of quinone redox potential

The quinones 1,4-naphthoquinone (NQ), methyl-1,4-naphthoquinone (MNQ), trimethyl-1,4-benzoquinone (TMQ) and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UQ-0) enhance the rate of nitric oxide (NO) reduction by ascorbate in nitrogen-saturated phosphate buffer (pH 7.4). The observed rate constants for this reaction were determined to be 16±2,215±6,290±14 and 462±18 M^-1 s^-1, for MNQ, TMQ, NQ and UQ-0, respectively. These rate constants increase with an increase in quinone one-electron redox potential at neutral pH, E₇¹. Since NO production is enhanced under hypoxia and under certain pathological conditions, the observations obtained in this work are very relevant to such conditions.     

The toxicity of menadione (2-methyl-1,4-naphthoquinone) and two thioether conjugates studied with isolated renal epithelial cells

Menadione (2-methyl-1,4-naphthoquinone) was used as a model compound to test the hypothesis that thioether conjugates of quinones can be toxic to tissues associated with their elimination through a mechanism involving oxidative stress. Unlike menadione, the glutathione (2-methyl-3-(glutathion-S-yl)-1,4-naphthoquinone; MGNQ) and N-acetyl-L-cysteine (2-methyl-3-(N-acetylcysteine-S-yl)-1,4-naphthoquinone; M(NAC)NQ) thioether conjugates were not able to arylate protein thiols but were still able to redox cycle with cytochrome c reductase/NADH and rat kidney microsomes and mitochondria. Interestingly, menadione and M(NAC)NQ were equally toxic to isolated rat renal epithelial cells (IREC) while MGNQ was nontoxic. The toxicity of both menadione and M(NAC)NQ was preceded by a rapid depletion of soluble thiols and was associated with a depletion of soluble thiols and was associated with a depletion of protein thiols. Treatment of IREC with the glutathione reductase inhibitor, 1,3-bis(2-chloroethyl)-1-nitrosourea, potentiated the thiol depletion and toxicity observed with menadione and M(NAC)NQ indicating the involvement of oxidative stress in this model of renal cell toxicity. The lack of MGNQ toxicity can be attributed to an intramolecular cyclization reaction which destroys the quinone nucleus and therefore eliminates its ability to redox cycle. These findings have important implications with regard to our understanding of the toxic potential of quinone thioether conjugates and of quinone toxicity in general.     

Insecticidal activities of a Diospyros kaki root-isolated constituent and its derivatives against Nilaparvata lugens and Laodelphax striatellus

Diospyros kaki root-derived materials were examined for insecticidal properties against Nilaparvata lugens and Laodelphax striatellus. Based on the LD₅₀ values, the chloroform fraction of D. kaki extracts showed the most activity against N. lugens (3.78 μg/female) and L. striatellus (7.32 μg/female). The active constituent of the chloroform fraction was isolated by various chromatographic methods and was identified as 5-hydroxy-2-methyl-1,4-naphthoquinone by spectroscopic analyses. To establish the structure–activity relationships, the insecticidal effects of 5-hydroxy-2-methyl-1,4-naphthoquinone and its derivatives against N. lugens and L. striatellus were determined using micro-topical application bioassays. On the basis of LD₅₀ values, 5-hydroxy-1,4-naphthoquinone was the most effective against N. lugens (0.072 μg/female) and L. striatellus (0.183 μg/female). 2-Bromo-1,4-naphthoquinone, 2-hydroxy-1,4-naphthoquinone, and 5-hydroxy-2-methyl-1,4-naphthoquinone also had potent insecticidal activities against N. lugens and L. striatellus. In contrast, no insecticidal activity was observed with 2-methoxy-1,4-naphthoquinone or 2-methyl-1,4-naphthoquinone. These results indicate that the functional group (bromo- and hydroxyl-) at the C-2 position of the 1,4-naphthoquinone skeleton and the change in position of the hydroxyl group play important roles in insecticidal activity. Therefore, naturally occurring D. kaki root-derived 5-hydroxy-2-methyl-1,4-naphthoquinone and its derivatives may be suitable as insecticides.     

Naphthoquinone inhibitors of Periplaneta americana and Scolytus multistriatus feeding: ultraviolet difference spectra of reactions of juglone, menadione, and 1,4-naphthoquinone with amino acids and the indicated mechanism of feeding inhibition

The relative reactivity of 3 naphthoquinones, which are feeding inhibitors for Periplaneta americana and Scolytus multistriatus, with each of 7 amino acids was measured by ultraviolet difference spectroscopy. Juglone (5-hydroxy-1,4-naphthoquinone), menadione(2-methyl-1,4-naphthoquinone) or 1,4-naphthoquinone produced difference spectra immediately upon mixing with cysteine, but not with valine, serine, glutamic acid, arginine, tryptophan or proline in phosphate buffer (pH 7.0). The K_s values for the reactions indicated that the affinities of 1,4-naphthoquinone (K_s = 4.4 · 10⁻⁴M) and juglone (K_s = 8.3 · 10⁻⁴M) for cysteine were comparable, but were both approx. 10 times greater than that for menadione (K_s = 3.2 · 10⁻³M). The extinction coefficient of the complex formed by cysteine with juglone (A = 3.448 · 10⁻¹M) was approx. 2 times greater than that of 1,4-naphthoquinone (A = 1.290 · 10⁻¹M) or menadione (A = 1.176 · 10⁻¹ M). The importance of these results to explaining the mechanism of chemoreception in P. americana and S. multistriatus is discussed.     

Anticancer activities of six selected natural compounds of some Cameroonian medicinal plants

Background

Natural products are well recognized as sources of drugs in several human ailments. In the present work, we carried out a preliminary screening of six natural compounds, xanthone V₁ (1); 2-acetylfuro-1,4-naphthoquinone (2); physcion (3); bisvismiaquinone (4); vismiaquinone (5); 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone (6) against MiaPaCa-2 pancreatic and CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000. Compounds 1 and 2 were then tested in several other cancer cells and their possible mode of action were investigated.

Methodology/Findings

The tested compounds were previously isolated from the Cameroonian medicinal plants Vismia laurentii (1, 3, 4, 5 and 6) and Newbouldia laevis (2). The preliminary cytotoxicity results allowed the selection of xanthone V₁ and 2-acetylfuro-1,4-naphthoquinone, which were then tested on a panel of cancer cell lines. The study was also extended to the analysis of cell cycle distribution, apoptosis induction, caspase 3/7 activation and the anti-angiogenic properties of xanthone V₁ and 2-acetylfuro-1,4-naphthoquinone. IC₅₀ values around or below 4 µg/ml were obtained on 64.29% and 78.57% of the tested cancer cell lines for xanthone V₁ and 2-acetylfuro-1,4-naphthoquinone, respectively. The most sensitive cell lines (IC₅₀<1 µg/ml) were breast MCF-7 (to xanthone V₁), cervix HeLa and Caski (to xanthone V₁ and 2-acetylfuro-1,4-naphthoquinone), leukemia PF-382 and melanoma colo-38 (to 2-acetylfuro-1,4-naphthoquinone). The two compounds showed respectively, 65.8% and 59.6% inhibition of the growth of blood capillaries on the chorioallantoic membrane of quail eggs in the anti-angiogenic assay. Upon treatment with two fold IC₅₀ and after 72 h, the two compounds induced cell cycle arrest in S-phase, and also significant apoptosis in CCRF-CEM leukemia cells. Caspase 3/7 was activated by xanthone V₁.

Conclusions/Significance

The overall results of the present study provided evidence for the cytotoxicity of compounds xanthone V₁ and 2-acetylfuro-1,4-naphthoquinone, and bring supportive data for future investigations that will lead to their use in cancer therapy.     

Cytotoxic activity of naphthoquinones with special emphasis on juglone and its 5-O-methyl derivative

The cytotoxicity of nine naphthoquinones (NQ) was assayed against HL-60 (leukaemia), MDA-MB-435 (melanoma), SF-295 (brain) and HCT-8 (colon), all human cancer cell lines, and peripheral blood mononuclear cells (PBMC), as representatives of normal cells, after 72 h of incubation. 5-Methoxy-1,4-naphthoquinone was the most active compound, showing IC₅₀ values in the range of 0.31 (1.7 μM) in HL-60 to 0.88 μg/mL (4.7 μM) in SF-295 and IC₅₀ of 0.69 μg/mL (3.7 μM) against PBMC. With the introduction of a bromo-substituent in position 2 or 3 of juglone, the IC₅₀ significantly decreased, regardless of the position on the NQ moiety. However, compared with juglone methyl ether, the halogen substitution decreased the activity. To further understand the mechanism underlying the cytotoxicity of 5-methoxy-1,4-naphthoquinone, studies involving DNA fragmentation, cell cycle analysis, phosphatidyl serine externalization, mitochondrial depolarization and activation of caspases 8 and 3/7 were performed in HL-60 cell line, using doxorubicin as a positive control. The results indicate that the cytotoxic 5-methoxy-1,4-naphthoquinone activates caspases 8 and 3/7 and thus induces apoptosis independent of mitochondria.     

A comparison of the effects of 1,4-naphthoquinone and 2-hydroxy-1,4-naphthoquinone (lawsone) on indole-3-acetic acid (IAA)-induced growth of maize coleoptile cells

The effects of 1,4-naphthoquinone (NQ) and 2-hydroxy-1,4-naphthoquinone (NQ-2-OH) on indole-3-acetic acid (IAA)-induced growth, medium pH changes and membrane potential (E_m) in maize (Zea mays L.) coleoptile cells were determined. In addition, the redox cycling properties of both naphthoquinones were also compared. The dose-response curves constructed for the effects of NQ and NQ-2-OH on endogenous and IAA-induced growth differ in shape. It was found that NQ was by 10–50% more effective in inhibiting IAA-induced growth in maize coleoptile segments than NQ-2-OH. Simultaneous measurements of growth and external medium pH indicated that NQ and NQ-2-OH reduced or eliminated proton extrusion at all of the concentrations used, excluding NQ at 1 µM. It was found that both naphthoquinones at concentrations higher than 10 µM caused the depolarisation of the membrane potential (E_m). Additionally, compared to the controls, NQ- and NQ-2-OH-exposure of coleoptile segments, at concentrations higher than 10 µM, caused an elevation of the hydrogen peroxide (H₂O₂) production and plasma membrane redox activity. The highest catalase activity was observed at 10 µM NQ and it was ca. 18-fold greater (at 4 h) than in the control medium. Moreover, it was also found that NQ and NQ-2-OH, at all concentrations studied, increased the malondialdehyde content of coleoptile segments at 4 h of the experiment. The data presented here are discussed taking into account the “acid growth hypothesis” of auxin action and the mechanisms by which naphthoquinones interact with biological systems.     

Investigation of the cumulative tissue doses of naphthoquinones in human serum using protein adducts as biomarker of exposure

Both 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ) are reactive metabolites of naphthalene that are thought to be responsible for the naphthalene-induced cytotoxicity and genotoxicity. The aim of this study was to investigate the cumulative tissue dose of 1,2-NPQ and 1,4-NPQ in human serum derived from blood donors in Taiwan via measurements of albumin adducts by a methodology, which employs trifluoroacetic acid anhydride and methanesulfonic acid to selectively cleave cysteinyl adducts on proteins. Both 1,2-NPQ and 1,4-NPQ adducts were detected in all male and female subjects (n = 22). The median levels of 1,2-NPQ adduct in human subjects were estimated to be 268 (range 139-857) and 203 (range 128-1352) (pmol/g) in male (n = 11) and female (n = 11) subjects, respectively. In contrast, the median levels of 1,4-NPQ adduct were estimated to be 45.0 (range 22.0-117) and 38.9 (range 21.5-172) (pmol/g) in male and female subjects, respectively. We noticed that levels of 1,2-NPQ adduct were significantly correlated with those of 1,4-NPQ adduct (correlation coefficient r = 0.643, p < 0.01). Results from in vitro experiments confirmed that the production of naphthoquinones-derived adducts on serum albumin increased with increased concentration of naphthoquinones (0-100 μM). Linear relationships were observed over the range of concentration. Time-course experiments suggested that both 1,2-NPQ and 1,4-NPQ-derived adducts rapidly reached maximum values at 10 min mark and remained constant thereafter. The reaction rate constant analyses indicated that the second-order rate constants, representing in vitro reactions between naphthoquinones and cysteine residues of serum albumin, were estimated to be 0.0044/0.0002 L(g protein)⁻¹ h⁻¹, respectively. Overall, the cumulative tissue doses of 1,4-NPQ (217-316 nM h) in male and female subjects were ∼3-fold greater than those of 1,2-NPQ (76-98 nM h) in the study population. The initial concentrations of serum 1,2-NPQ and 1,4-NPQ in the study population were estimated to be between 145-188 and 807-1175 nM, respectively. We conclude that the relatively large amounts of naphthoquinones present in human serum may point to toxicological consequences.     

Superoxide anion as a mediator of drug-induced oxidative hemolysis.

The superoxide dismutase inhibitor diethyldithiocarbamate (DDC) was utilized to study the toxic effect of 1,4-naphthoquinone 2-sulfonate (NQ), a structural analog of the hemolytic drug, menadione, on red cells. NQ was shown to react with hemoglobin and result in the generation of superoxide anion (O2-). Red cells treated with NQ were found to undergo a gradual disappearance of their oxyhemoglobin and also hemolyze. Red cells pretreated with DDC to inhibit cellular superoxide dismutase were found to be markedly sensitive to oxyhemoglobin destruction and hemolysis in the presence of NQ. Superoxide dismutase-inhibited red cells were also found to undergo a slow autohemolysis in the absence of NQ. No evidence for lipid peroxidation was obtained for red cells treated with NQ either in the presence or the absence of DDC. Ghosts prepared from superoxide dismutase-inhibited red cells exposed to NQ were found to retain a green hemoglobin-derived pigment.     

Studies on Effects of Certain Quinones: II. Photosynthetic Incorporation of CO(2) by Chlorella

The effects of various quinone herbicides and fungicides on the photosynthetic ¹⁴CO₂ fixation and the incorporation of ¹⁴C among the products of photosynthesis in Chlorella pyrenoidosa was investigated. Addition of 30 μm 2,3-dichloro-1,4-naphthoquinone (dichlone), 2-amino-3-chloro-1,4-naphthoquinone (06K-quinone), or 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil) inhibited CO₂ fixation, whereas 1,4-benzoquinone had no effect. Treatment with 3 μm or higher concentrations of dichlone, 06K-quinone or 1,4-benzoquinone also produced marked changes in the pattern of ¹⁴C distribution. A noticeable effect was an increase in the proportion of ¹⁴C in sucrose and glycine accompanied by a reduction in ¹⁴C lipids and glutamic acid. These changes appear to occur as a result of shifts in the flow of carbon along various biosynthetic pathways of photosynthetic CO₂ fixation. It is suggested that inactivation of coenzyme A and shortage of reduced triphosphopyridine nucleotide in the quinone-treated cells inhibited the synthesis of lipids and glutamic acid, thereby diverting more carbon into sucrose and glycine.     

Biologically Active Metabolites Produced by the Basidiomycete Quambalaria cyanescens

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

Menadione sodium bisulfite inhibits the toxic aggregation of amyloid-β(1–42)

Protein misfolding and aggregation are associated with amyloidosis. The toxic aggregation of amyloid-β 1–42 (Aβ42) may disrupt cell membranes and lead to cell death and is thus regarded as a contributing factor in Alzheimer's disease (AD). 1,4-naphthoquinone (NQ) has been shown to exhibit strong anti-aggregation effects on amyloidogenic proteins such as insulin and α-synuclein; however, its high toxicity and poor solubility limit its clinical application. Menadione sodium bisulfite (MSB, also known as vitamin K3), is used clinically in China to treat hemorrhagic diseases caused by vitamin K deficiency and globally as a vitamin K supplement. We hypothesized that MSB could inhibit amyloid formation since its backbone structure is similar to NQ. To test our hypothesis, we first investigated the effects of MSB on Aβ42 amyloid formation in vitro. We found that MSB inhibited Aβ42 amyloid formation in a dose dependent manner, delayed the secondary structural conversion of Aβ42 from random coil to ordered β-sheet, and attenuated the ability of Aβ42 aggregates to disrupt membranes; moreover, the quinone backbone rather than lipophilicity is esstial for the inhibitory effects of MSB. Next, in cells expressing a pathogenic APP mutation (Osaka mutation) that results in the formation of intraneuronal Aβ oligomers, MSB inhibited the intracellular aggregation of Aβ. Moreover, MSB treatment significantly extended the life span of Caenorhabditis elegans CL2120, a strain that expresses human Aβ42. Together, these results suggest that MSB and its derivatives may be further explored as potential therapeutic agents for the prevention or treatment of AD.     

Firefly Courtship: Behavioral and Morphological Predictors of Male Mating Success in Photinus greeni

Differences in male mating success can generate selection on male morphological traits and courtship behaviors involved in male–male competition or female mate choice. In Photinus fireflies (Coleoptera: Lampyridae), courtship is based on bioluminescent flash signals produced by both sexes. We conducted field observations of Photinus greeni fireflies engaged in competitive courtships, in which females are able to simultaneously assess several males, to identify male morphological traits and courtship behaviors that might predict male mating success. Male morphological traits did not differ between males that successfully mated compared with unsuccessful males (dialoging males that did not mate). However, courtship behavioral interactions differed: successful males tended to have higher flash pattern rates (number of flash patterns per minute), and their courtship flashes were more likely to be answered by females. We also examined how the risk of predation by Photuris fireflies altered courtship behavior of their Photinus prey. When predatory Photuris fireflies were present, P. greeni females were less likely to mate, and showed decreased flash responses to most males. However, P. greeni males that did successfully mate in spite of Photuris presence were males that maintained high flash pattern rates that elicited female responses. These results suggest that both female mate choice and Photuris predation exert strong selective pressures on the evolution of courtship signals in Photinus fireflies.     

Spontaneous flash communication of females in an Asian firefly

Fireflies are well known for the use of bioluminescence for sexual communication. In species using flash signals for pair formation, species and sexual identity are conferred by flash timing parameters such as flash duration, flash interval, flash number, and response delay. In dialog fireflies in North America, the male is the advertiser and the female is the responder. In these species, the male flash signal parameter varies depending on species, but the female flash signal parameter is limited only to response delay. However, in fireflies other than dialog fireflies, sexual flash communication is not well studied. Although many female-advertisement-like fireflies are reported, we have no confirmed case of sexual communication in a female-advertisement species. Here, we report the sexual flash communication of an Asian firefly, Luciola (Hotaria) parvula, in which the female flashes spontaneously. By using an electronic firefly, we confirm experimentally that males are specifically attracted to flashes with a female-specific flash duration. This is the first experimental report of sexual communication of a female advertiser in firefly communication. In this species, females call males usually with spontaneous flashes unlike dialog fireflies.     

Inhibition of Ca2+-activated and voltage-dependent K+ currents by 2-mercaptophenyl-1,4-naphthoquinone in pituitary GH3 cells: contribution to its antiproliferative effect

Quinones have been shown to possess antineoplastic activity; however, their effects on ionic currents remain unclear. The effects of 2-mercaptophenyl-1,4-naphthoquinone (2-MPNQ), menadione (MD) and 1,4-naphthoquinone (1,4 NQ) on cell proliferation and ionic currents in pituitary GH3 lactotrophs were investigated in this study. 2-MPNQ was more potent than menadione or 1,4-naphthoquinone in inhibiting the growth of GH3 cells. 2-MPNQ decreased cell proliferation in a concentration-dependent manner with an IC50 value of 3 microM. In whole-cell recording experiments, 2-MPNQ reversibly caused an inhibition of Ca2+-activated K+ current (I(K(Ca)) in a concentration-dependent manner. The IC50 value for 2-MPNQ-induced inhibition of I(K(Ca)) was 7 microM. In the inside-out configuration of single channel recording, 2-MPNQ (30 microM) applied intracellularly suppressed the activity of large-conductance Ca2+-activated K+ (BK(Ca)) channels but did not modify single channel conductance. Menadione (30 microM) had no effect on the channel activity, whereas 1,4-naphthoquinone (30 microM) suppressed it by about 26%. Both 2-MPNQ and thimerosal suppressed the dithiothreitol-stimulated channel activity. 2-MPNQ also blocked voltage-dependent K+ currents, but it produced a slight reduction of L-type Ca2+ inward current. However, unlike E-4031, 2-MPNQ (30 microM) did not suppress inwardly rectifying K+ current present in GH3 cells. Under the current clamp configuration, the presence of 2-MPNQ (30 microM) depolarized the cells, and increased the frequency and duration of spontaneous action potentials. The 2-MPNQ-mediated inhibition of K+ currents would affect hormone secretion and cell excitability. The blockade of these ionic channels by 2-MPNQ may partly explain its inhibitory effect on the proliferation of GH3 cells.     

In vitro antiamyloidogenic properties of 1,4-naphthoquinones

The aim of this study is to find out whether several 1,4-naphthoquinones (1,4-NQ) can interact with the amyloidogenic pathway of the amyloid precursor protein processing, particularly targeting at β-secretase (BACE), as well as at β-amyloid peptide (Aβ) aggregation and disaggregating preformed Aβ fibrils. Compounds bearing hydroxyl groups at the quinoid (2) or benzenoid rings (5, 6) as well as some 2- and 3-aryl derivatives (11-15) showed BACE inhibitory activity, without effect on amyloid aggregation or disaggregation. The halogenated compounds 8 and 10 were selective for the inhibition of amyloid aggregation. On the other hand, 1,4-naphthoquinone (1), 6-hydroxy-1,4-naphthoquinone (4) and 2-(3,4-dichlorophenyl)-1,4-naphthoquinone (26) did not show any BACE inhibitory activity but were active on amyloid aggregation and disaggregation preformed Aβ fibrils. Juglone (5-hydroxy-1,4-naphthoquinone (3), and 3-(p-hydroxyphenyl)-5-methoxy-1,4-napththoquinone (19) were active on all the three targets. Therefore, we suggest that 1,4-NQ derivatives, specially 3 and 19, should be explored as possible drug candidates or lead compounds for the development of drugs to prevent amyloid aggregation and neurotoxicity in Alzheimer’s disease.