• Archives of Pharmacal Research
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• v.29 no.2
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• pp.123-130
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• 2006

1,4-Naphthoquinones are widely distributed in nature and many clinically important antitumor drugs containing a quinone moiety, such as anthracyclines, mitoxantrones and saintopin, show excellent anticancer activity. In this study, 2- or 6-substituted 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) and 5,8-dihydroxy-1,4-naphthoquinone (DHNQ) derivatives were synthesized, and their cytotoxic activity against L1210 and P388 cancer cells was examined. Their antitumor activity was also assessed in mice bearing S-180 cells in the peritoneal cavity. In comparison with the DMNQ derivatives, the DHNQ derivatives exhibited more potent bioactivities than the DMNQ derivatives against both L1210 and P388 cells in vitro and S-180 cells in vivo. The $ED_{50}$ values of the DHNQ derivatives against P388 cells were in the range of 0.18-1.81 ${\mu}g/mL$ whereas those of the DMNQ derivatives were in the range of 0.26-40.41 ${\mu}g/mL$. The T/C ($\%$) values of the DHNQ derivatives, 8, 17, 18, 19, and 20, were found to be comparable to or even better than that of adriamycin. It was also observed that the 2-substituted derivatives (8, 19, 20) showed better antitumor activity than the 6-substituted derivatives (7, 17, 18) in the mice bearing S-180 cells in the peritoneal cavity.

• Applied Biological Chemistry
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• v.46 no.3
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• pp.268-270
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• 2003

Methanol extract obtained from aerial parts of Platycarya strobilacea was successively fractionated with n-hexane, ethylacetate, n-butanol, and water. From ethylacetate fraction, an active compound was isolated through repeated silica gel column chromatography and was identified as 5-hydroxy-2-methoxy-1,4-naphthoquinone by MS and NMR analyses. The compound showed in vivo 76% antifungal activity at $100\;{\mu}g/ml$ against tomato late blight disease.

• Applied Biological Chemistry
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• v.32 no.1
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• pp.30-36
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• 1989

Some chelating agents are evaluated as an antioxidant for the autoxidation of soybean oil. Soybean oil is autoxidized under a mild condition (the flow rate of 67ml $O_{2}/min$ and $50^{\circ}C$). The antioxidant effect is measured by active oxygen method, and the spectral change of autoxidized soybean oil examined. The antioxidant effect of chelating agents is increased in order of diphenic acid, naphthoquinone, pyromellitic acid, quinolinic acid and naphthalic acid, and particularly the effect is low in diphenic acid and naphthoquinone. It is found that the effect is more clearly demonstrated by NMR rather than IR and UV and that the effect is dependent on the functional group and geometric molecular structure of chelating agents.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.109-109
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• 1997

Inhibitory effect on DNA topoisomerase-I, rate of glutathione conjugation and cytotoxicity of naphthoquinone derivatives were correlated. During 5 min exposure of the derivatives to glutathione (GSH), it was found that 14% of 5,8-dimethoxy-1,4-naphthoquinone(DMNQ) was converted into a GSH-conjugate, whereas 5,8-dihydroxy-1,4-naphthoquinone(DHNQ) did not interact with GSH, implying that DMNQ exerted higher electrophilicity than DHNQ. However, DHNQ (IC$\_$50/, 0.15 ${\mu}$M) showed stronger cytotoxicity in L1210 cells than DMNQ(IC$\_$50/, 0.45 ${\mu}$M). The stronger cytotoxicity of DHNQ, compared to DMNQ, could be ascribed to more rapid redox cycling. Both naphthoquinones (IC$\_$50/, 60-65 ${\mu}$M) exhibiting about the same inhibitory effect on DNA topoisomerase-I were more potent than 1,4-naphthoquinone(1,4-NQ, IC$\_$50/, 134 ${\mu}$M). Thus, 5,8-oxy groups in the structure seem to be important for the inhibition of the enzyme. DMNQ showed a broader dose range while maintaining a good antitumor activity against S-180 fluid tumor. For these reasons, DMNQ was taken as useful pharmacophore for structural modification. Introduction of 1-hydroxyalkyl groups at C-2 of DMNQ lowered all of the activities mentioned above, while acetylation of 1-hydroxyalkyl moiety enhanced the activities by 4-5 times. Introduction of the same side chains at C-6 exhibited stronger activities than 2-substituted ones. Based on these results it was suggested that the quinonoid moiety in 6-substituted DMNQ was more exposed to cellular nucleophiles such as DNA, thiols of enzymes and so on. The synthesis of DHNQ or DMNQ derivatives are going on, and the corelationship between structure-activity will be discussed.

• Bulletin of the Korean Chemical Society
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• v.28 no.4
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• pp.691-694
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• 2007

• Ecology and Resilient Infrastructure
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• v.4 no.3
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• pp.130-141
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• 2017

We evaluated the field application feasibility that biologically derived substances (Naphthoquinone derivate: NQ 2-0) can be used for the eco-friendly mitigation of natural harmful cyanobacterial blooms in freshwater. We conducted a 30 ton scale mesocosm experiment to investigate the effects of NQ 2-0 on biotic and abiotic factors in water collected from Gi-heung reservoir. In the mesocosm experiments, the abundance of Microcystis sp. was continuously increased in the control. However, the Microcystis sp. cell density was sharply decreased on the $10^{th}$ day. In the treatment, NQ 2-0 showed the strong and selective algicidal activity toward the target cyanobacteria (Microcystis sp.). Accordingly, the algicidal activity of NQ 2-0 compound increased gradually until $10^{th}$, $15^{th}$ days and algal biomass was decreased to 99.4 and 100 %, respectively. NQ 2-0 compound was not only selective algicidal activity but also the growth of other phytoplankton and increased the Shannon-Wiener diversity index of phytoplankton. In the mesocosm experiments, the dynamics of biotic (bacteria, heterotrophic nanoflagellate, ciliates, zooplankton) and abiotic (water temperature, dissolved oxygen, pH, conductivity, nutrients) factors remained unaffected. These results suggest that NQ 2-0 could be a selective and ecologically safe algicide to mitigate harmful cyanobacterial blooms. In addition, it is believed that NQ 2-0 will play a major role in forming a healthy aquatic ecosystem by facilitating habitat and food supply of aquatic organisms.

• Ecology and Resilient Infrastructure
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• v.3 no.1
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• pp.22-34
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• 2016

We developed a biologically-derived substance naphthoquinone (NQ) derivate for the eco-safe mitigation of harmful cyanobacteria blooms such as Microcystis and Dolichospermum. NQ was reacted with various substituents ($R_n$) to produce different NQ derivatives. We tested a total of 92 algicidal compounds based on the algicidal activity of Microcystis and Dolichospermum. 22 compounds of NQ were selected as candidates (algicidal activity >80% at $1{\mu}M$). Among them, NQ 40 compound showed the highest algicidal activity of 99.6% and 100% at the optimal concentration of $1{\mu}M$ on Microcystis and Dolichospermum, respectively. No algicidal effects of NQ 40 ($1{\mu}M$) were observed against non-target algae such as Stephanodiscus, Cyclotella and Peridinium. According to the results of acute eco-toxicity assessment, the $EC_{50}$ values of NQ 40 compound for Selenastrum capricornutum and Daphnia magna were 3.2 and $14.5{\mu}M$, respectively, and the $LC_{50}$ for Danio rerio was $15.7{\mu}M$. In addition, for D. magna chronic eco-toxicity assessment, no toxicity toward survival, growth and reproduction was observed. Therefore, we suggested the NQ 40 ($1{\mu}M$) compound as an alternative eco-safe algicidal substance to effectively mitigate harmful cyanobacteria blooms.

• Ecology and Resilient Infrastructure
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• v.7 no.1
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• pp.72-81
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• 2020

Blooms of the small centric diatom Stephanodiscus is quite occasional in winter season in temperate freshwater ecosystems. Often, it leads to degradation of water quality and affects quality of supplied drinking water. In previous studies, naphthoquinone (NQ) compounds have been shown to be effective and selective for controlling winter bloom species Stephanodiscus hantzschii. We conducted a 5 ton scale mesocosm experiment to investigate the effects of NQ on native Stephanodiscus sp. collected from Nakdonggang River in water. After treatment with NQ 4-6 compound (0.2 μM), the cell density of Stephanodiscus sp. was rapidly reduced from 5 × 10³ cells mL^-1 to 0.2 × 10³ cells mL^-1 for 10 days. Additionally, NQ 4-6 compound did not affect physicochemical factors (water temperature, dissolved oxygen, pH, conductivity, nutrients) and biological factors (bacteria, heterotrophic nanoflagellates, zooplankton). Therefore, these findings suggest that the NQ 4-6 compound has potential as an alternative algicidal substances to effectively mitigate natural Stephanodiscus sp. blooms, and the application of NQ 4-6 compound will restore the healthy aquatic ecosystems.

• Korean Journal of Pharmacognosy
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• v.27 no.3
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• pp.238-245
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• 1996

The activity guided fractionation of $CH_2Cl_2$ soluble part of Platycarya strobilacea leaves(Juglandaceae) has led to the isolation of eight active principles, identified as 5-hydroxy-2-methoxy-1,4-naphthoquinone(1), ursolic acid(2), gallic acid(3), 4,8-dihydroxynaphthalene $1-O-{\beta}-_D-glucoside(4)$, eriodictyol(5), quercetin $3-O-(2'-O-galloyl)-{\beta}-_D-glucoside(6)$. quercetin $3-O-(2'-O-galloyl)-{\beta}-_D-galactoside(7)$ and quercetin $3-O-{\alpha}-_L-rhamnoside(8)$ by the means of chemical and spectral evidence, respectively.

• Korean Journal of Environmental Biology
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• v.38 no.1
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• pp.114-126
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• 2020

Bloom-forming toxic cyanobacteria Microcystis spp. are common in the summer season in temperate freshwater ecosystems. Often, it leads to the degradation of water quality and affects the quality of drinking water. In a previous study, NQ (naphthoquinone) compounds were shown to be effective, selective, and ecologically safe algicides for Microcystis spp. blooms. To analyze the superiority of developed NQ derivatives, we conducted a microcosm experiment using clay, which is frequently used in South Korea. Similar to previous studies, the NQ 40 and NQ 2-0 compounds showed high algicidal activities of 99.9% and 99.6%, respectively, on Microcystis spp. at low concentrations (≥1 μM) and enhanced phytoplankton species diversity. However, when treated with clay, a temporary algicidal effect was seen at the beginning of the experiment that gradually increased at the end. In addition, treatment with the NQ compounds did not affect either the abiotic or biological factors, and similar trends were observed with the control. These results showed that the NQ 2-0 compound was more effective, with no ecosystem disturbance, and more economical than the currently used clay. These results suggest that NQ 2-0 compound could be a selective, economically and ecologically safe algicide to mitigate harmful cyanobacterial blooms in the field.