Naphthoquinones and their pharmacological properties

Veterinární a farmaceutická univerzita Brno, Farmaceutická fakulta, Ustav prírodních léciv.
Ceská a Slovenská farmacie: casopis Ceské farmaceutické spolecnosti a Slovenské farmaceutické spolecnosti 07/2007; 56(3):114-20.
Source: PubMed


Naphthoquinones are wide-spread phenolic compounds in nature. They are products of bacterial and fungal as well as high-plants secondary metabolism. Juglone, lawsone, and plumbagin are the most widespread compounds. Naphthoquinones display very significant pharmacological properties--they are cytotoxic, they have significant antibacterial, antifungal, antiviral, insecticidal, anti-inflammatory, and antipyretic properties. Pharmacological effects to cardiovascular and reproductive systems have been demonstrated too. The mechanism of their effect is highly large and complex--they bind to DNA and inhibit the processes of replication, interact with numerous proteins (enzymes) and disturb cell and mitochondrial membranes, interfere with electrons of the respiratory chain on mitochondrial membranes. Plants with naphthoquinone content are widely used in China and the countries of South America, where they are applied to malignant and parasitic diseases treatment.

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    • "A quinone usually has several pharmacological effects. For example, 1,4-naphthoquinone exhibits antibacterial, antifungal, and antitumor activities (Babula et al., 2007), and its derivatives, plumbagin and lawsone, also display diverse antitumor activities (Kawiak et al., 2007; Wang et al., 2008). On the other hand, quinones can induce a variety of serious toxic effects in vivo, including cytotoxicity, immunotoxicity and carcinogenesis (Bolton et al., 2000), and therefore they are also of interest to toxicologists. "
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    ABSTRACT: Bostrycin is an anthracenedione with phytotoxic and antibacterial activity that belongs to the large family of quinones. We have isolated bostrycin from the secondary metabolites of a mangrove endophytic fungus, no. 1403, collected from the South China Sea. Using the yeast Saccharomyces cerevisiae as a model, we show that bostrycin inhibits cell proliferation by blocking the cell cycle at G1 phase and ultimately leads to cell death in a time- and dose-dependent manner. Bostrycin-induced lethal cytotoxicity is accompanied with increased levels of intracellular reactive oxygen species and hallmarks of apoptosis such as chromatin condensation, DNA fragmentation and externalization of phosphatidylserine. We further show that bostrycin decreases mitochondrial membrane electric potential and causes mitochondrial destruction during the progression of cell death. Bostrycin-induced cell death was promoted in YCA1 null yeast strain but was partially rescued in AIF1 null mutant both in fermentative and respiratory media, strongly indicating that bostrycin induces apoptosis in yeast cells through a mitochondria-mediated but caspase-independent pathway.
    FEMS Yeast Research 03/2010; 10(3):297-308. DOI:10.1111/j.1567-1364.2010.00615.x · 2.82 Impact Factor
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    • "These results are consistent with a recently reported study where juglone and plumbagin were shown to cause oxidative stress in keratinocytes (Inbaraj and Chignell, 2004). Further, menadione, another plantderived quinone with anticancer property, exerts its activity via depletion of GSH (Babula et al., 2007). Juglone-induced oxidative stress was further confirmed by measuring the intracellular levels of ROS using DCFH-DA assay. "
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    ABSTRACT: This study demonstrates cytotoxic and genotoxic potential of juglone, a chief constituent of walnut, and its underlying mechanisms against melanoma cells. MTT assay and clonogenic assay were used to study cytotoxicity, micronucleus assay to assess genotoxicity, glutathione (GSH) assay and 2',7'-dicholorofluorescein diacetate (DCFH-DA) assay to evaluate the oxidative stress induction. Apoptosis/necrosis induction was analysed by flow cytometry. We observed a concentration-dependent decrease in cell survival with a corresponding increase in the lactate dehydrogenase levels. A dose-dependent increase in the frequency of micronucleated binucleate cells indicated the potential of juglone to induce cytogenetic damage in melanoma tumor cells. Moreover, results of the micronuclei study indicated division delay in the proliferating cell population by showing decrease in the cytokinesis blocked proliferation index. Further, juglone-induced apoptosis and necrosis could be demonstrated by oligonucleosomal ladder formation, microscopic analysis, increase in the hypodiploid fraction (sub Go peak in DNA histogram), as well as an increased percentage of AnnexinV(+)/PI(+) cells detected by flow cytometry. A significant concentration-dependent decrease in the glutathione levels and increase in dichlorofluorescein (DCF) fluorescence after juglone treatment confirmed the ability of juglone to generate intracellular reactive oxygen species. The cytotoxic effect of juglone can be attributed to mechanisms including the induction of oxidative stress, cell membrane damage, and a clastogenic action leading to cell death by both apoptosis and necrosis.
    Cell Biology International 10/2009; 33(10):1039-49. DOI:10.1016/j.cellbi.2009.06.018 · 1.93 Impact Factor
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    • "Among the many natural and synthetic compounds explored for anticancer potential, compounds with quinone containing moieties form a major part. Quinones, particularly 1,4-naphthoquinones are widely distributed phenolic compounds in nature and these naphthoquinones are reported to exhibit diverse pharmacological properties like antibacterial, antifungal , antiviral, anti-inflammatory and antipyretic properties including anticancer activity (Kim et al., 2006; Babula et al., 2007). These quinones with the ability to induce oxidative stress are responsible for initiation of tissue damage selectively in tumor cells and this seems to be a promising approach for targeting cancer cells (Smith et al., 1985). "
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    ABSTRACT: Quinones have diverse pharmacological properties including antibacterial, antifungal, antiviral, anti-inflammatory, antipyretic and anticancer activity. The cytotoxic potential of 1,4-naphthoquinone (NQ14) was studied against B16F1 melanoma cells grown in vitro. NQ14 treatment resulted in a concentration-dependent cytotoxicity as indicated by MTT assay and lactate dehydrogenase leakage assay. Depletion in cellular glutathione levels after 1h incubation with NQ14 correlated with the corresponding increase in reactive oxygen species generation as determined by 2',7'-dicholorofluorescein diacetate assay suggests the role of oxidative stress in cell death. The frequency of micronucleated binucleate cells increased with increasing doses of NQ14 with a corresponding decrease in the cytokinesis block proliferation index indicating the drug induced genotoxicity and cell division delay. Further, a dose-dependent decrease in the clonogenic cell survival indicated the potential of NQ14 to inhibit cell proliferation contributing to cell death. The cell death after NQ14 treatment may be attributed to apoptosis as seen in DNA ladder pattern along with necrosis as indicated in flow cytometric analysis of Annexin V/PI stained cells. Results of the present study demonstrate the cytotoxic and genotoxic potential of NQ14 by the induction of oxidative stress mediated mechanisms leading to tumor cell kill.
    Toxicology in Vitro 03/2009; 23(2):242-50. DOI:10.1016/j.tiv.2008.12.004 · 2.90 Impact Factor
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