naphthoquinones and 7-methyljuglone

Naphthoquinone is a class of phenolic compounds derived from naphthalene. 7-Methyljuglone (7-MJ) is a naphthoquinone also known as ramentaceone or 6-Methyl-8-hydroxy-1,4-naphthoquinone or 5-Hydroxy-7-methyl-1,4-naphthoquinone or 7-Methyl-5-hydroxy-1,4-naphthoquinone or 5-Hydroxy-7-methyl-,1,4-naphtoquinone or 7-Methyl-5-hydroxynaphthalene-1,4-dione. This compound is a biologically active naphtoquinone, with a molecular weight of 188 g/mol mostly isolated in the genus Diospyros and Euclea.. This review was aimed at providing available chemically and pharmacological data on 7-MJ.. The chemical and pharmacological data were retrieved from the well-known scientific websites such as Pubmed, Google Scholar, Reaxys, Scirus, Scopus, Sciencedirect, Web-of-knowledge and Scifinder.. 7-MJ was reported to have a variety of pharmacological activities such as antibacterial, antifungal, anticancer, antitubercular, anti-inflammatory and antiviral activities. The hemi-synthesis of the compound have been described.. The present review pooled out together the knowledge on 7-MJ, and can serve as the start point for future research and valorization accomplishments.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antitubercular Agents; Antiviral Agents; Biosynthetic Pathways; Humans; Naphthoquinones

The phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in processes critical for breast cancer progression and its upregulation confers increased resistance of cancer cells to chemotherapy and radiation. The present study aimed at determining the activity of ramentaceone, a constituent of species in the plant genera Drosera, toward breast cancer cells and defining the involvement of PI3K/Akt inhibition in ramentaceone-mediated cell death induction. The results showed that ramentaceone exhibited high antiproliferative activity toward breast cancer cells, in particular HER2-overexpressing breast cancer cells. The mode of cell death induced by ramentaceone was through apoptosis as determined by cytometric analysis of caspase activity and Annexin V staining. Apoptosis induction was found to be mediated by inhibition of PI3K/Akt signaling and through targeting its downstream anti-apoptotic effectors. Ramentaceone inhibited PI3-kinase activity, reduced the expression of the PI3K protein and inhibited the phosphorylation of the Akt protein in breast cancer cells. The expression of the anti-apoptotic Bcl-2 protein was decreased and the levels of the pro-apoptotic proteins, Bax and Bak, were elevated. Moreover, inhibition of PI3K and silencing of Akt expression increased the sensitivity of cells to ramentaceone-induced apoptosis. In conclusion, our results indicate that ramentaceone induces apoptosis in breast cancer cells through PI3K/Akt signaling inhibition. These findings suggest further investigation of ramentaceone as a potential therapeutic agent in breast cancer therapy, in particular HER2-positive breast cancer.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Caspases; Cell Line, Tumor; Cell Proliferation; Drosera; Enzyme Activation; Female; Humans; Naphthoquinones; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Signal Transduction

This study was designed to evaluate the antihyperalgesic effect of crude extract of Diospyros lotus followed by the isolation and characterisation of 7-methyljuglone in acetic acid and formalin tests. The pretreatment of crude extract evoked dose-dependent inhibition of noxious stimulation with maximum effect of 56.78% in acetic acid-induced writhing test, which were 51.89% and 60.69% in first and second phases, respectively, at 100 mg/kg i.p. The structure of 7-methyljuglone was confirmed by spectroscopic analysis. 7-Methyljuglone evoked profound increase in pain threshhold dose dependently; when it was studied in acetic acid-induced writhing test with 63.73% pain attenuation while 51.22% and 65.44% pain amelioration in first and second phases, respectively, at 100 mg/kg i.p. In conclusion, crude extract and 7-methyljuglone of D. lotus roots possessed both peripheral and central antinociceptive potential and thus could be a useful new therapeutic agent.

Topics: Analgesics; Animals; Diospyros; Female; Male; Mice, Inbred BALB C; Molecular Structure; Naphthoquinones; Pain; Plant Extracts; Plant Roots

Ramentaceone (1) is a naphthoquinone constituent of Drosera aliciae that exhibits potent cytotoxic activity against various tumor cell lines. However, its molecular mechanism of cell death induction has still not been determined. The present study demonstrates that 1 induces apoptosis in human leukemia HL-60 cells. Typical morphological and biochemical features of apoptosis were observed in 1-treated cells. Compound 1 induced a concentration-dependent increase in the sub-G1 fraction of the cell cycle. A decrease in the mitochondrial transmembrane potential (ΔΨm) was also observed. Furthermore, 1 reduced the ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax and Bak, induced cytochrome c release, and increased the activity of caspase 3. The generation of reactive oxygen species (ROS) was detected in 1-treated HL-60 cells, which was attenuated by the pretreatment of cells with a free radical scavenger, N-acetylcysteine (NAC). NAC also prevented the increase of the sub-G1 fraction induced by 1. These results indicate that ramentaceone induces cell death through the ROS-mediated mitochondrial pathway.

Topics: Acetylcysteine; Antineoplastic Agents, Phytogenic; Apoptosis; Drosera; Drug Screening Assays, Antitumor; Free Radical Scavengers; HL-60 Cells; Humans; Mitochondria; Molecular Structure; Naphthoquinones; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species

While the 1,4-naphthoquinone derivatives 7-methyljuglone (1) and plumbagin (2) possess a diverse and well documented array of biological activities, relatively little remains known about the functional significance of these compounds in planta and, in particular, their possible relation to carnivorous syndromes. In addition, the chemotaxonomic distribution of naphthoquinones (NQs) amongst species of Drosera L. is of phytopharmaceutical interest. Following the quantitative assessment of interspecific variation of 1 and 2 in 13 species and cultivars of Drosera, our findings demonstrate that these NQs are ubiquitously coproduced in, generally, species-specific ratios, and that 1 appears negatively associated with the occurrence of pigmentation in sundews. The prospective antifeedant function of 1 was evaluated in relation to allocation in various organs and ontogenetic phases of D. capensis L., revealing that significantly higher levels were accumulated in young and reproductive organs, most likely for defensive purposes. Investigation into the relationship between the biosynthesis of NQs and carnivory showed that production of 1 is optimally induced and localized in leaves in response to capture of insect prey. As a whole, these findings reveal the clear importance of this secondary metabolite in ecological interactions as well as holding implication for future bioactivity studies on the genus.

Topics: Drosera; Ecological and Environmental Phenomena; Naphthoquinones; Plant Extracts

Much correlative evidence indicates that the oxidative modification of protein by reactive oxygen species (ROS) is involved in normal aging as well as the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. In this study, we explored the antioxidative and neuroprotective effects of a naphthoquinone, 2-methoxy-6-acetyl-7-methyljuglone (MAM), purified from the dried rhizome of POLYGONUM CUSPIDATUM (Chinese name Hu-Zhang). Pretreatments with MAM (24 h) were investigated for their protective effects against apoptosis induced by the oxidizing agent TERT-butyl hydroperoxide ( T-BHP) in PC12 cells. The results indicated that MAM pretreatments could effectively protect PC12 cells against cytotoxicity induced by T-BHP in a dose-dependent manner. Cell viability was determined by both MTT and LDH assays. Increasing concentrations of MAM enhanced cell viability significantly and completely prevented cell death induced by T-BHP at 2.5 µM. The corresponding extracellular lactate dehydrogenase (LDH) levels were also attenuated significantly by various concentrations of MAM. In addition, it was found that the antioxidative effect of MAM was stronger than those of resveratrol and lipoic acid. The antiapoptotic property of MAM was further investigated with Hoechst 33342 nuclear staining and TUNEL assay. Pretreatments of MAM were able to prevent the T-BHP-induced nucleus fragmentation and accumulation of apoptotic bodies (commonly accepted as markers of apoptosis) inside the cells in a dose-dependent manner. T-BHP induced the phosphorylation of ERK 1/2, JNK and p38 MAPK, which were all impeded by pretreatments with MAM, indicating that MAM may act as a potent antioxidant which significantly interferes with the MAPK apoptotic cascades, probably rescuing cells by inhibiting the death pathways.

Topics: Animals; Antioxidants; Apoptosis; Cell Nucleus; Cell Survival; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Fallopia japonica; L-Lactate Dehydrogenase; Mitogen-Activated Protein Kinases; Naphthoquinones; Neuroprotective Agents; PC12 Cells; Phosphorylation; Rats; Resveratrol; Rhizome; Stilbenes; tert-Butylhydroperoxide; Thioctic Acid

The naphthoquinone 7-methyljuglone (5-hydroxy-7-methyl-1,4-naphthoquinone) has previously been isolated and identified as an active component of root extracts of Euclea natalensis which displays antitubercular activity. Herein, a series of synthetic and plant-derived naphthoquinone derivates of the 7-methyljuglone scaffold have been prepared and evaluated for antibacterial activity against Mycobacterium tuberculosis. Several of these compounds have been shown to operate as subversive substrates with mycothiol disulfide reductase. The absence of a direct correlation between antitubercular activity and subversive substrate efficiency with mycothiol disulfide reductase, might be a consequence of their non-specific reactivity with multiple biological targets (e.g. other disulfide reductases).

Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Ebenaceae; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; NADH, NADPH Oxidoreductases; Naphthoquinones; Plant Roots

The recent increase in the incidence of tuberculosis with the emergence of multidrug-resistant (MDR) cases has lead to the search for new drugs that are effective against MDR strains of Mycobacterium tuberculosis and can augment the potential of existing drugs against tuberculosis. In the present study, we investigated the activities of a naphthoquinone, 7-methyljuglone, isolated from the roots of Euclea natalensis alone and in combination with other antituberculous drugs against extracellular and intracellular M. tuberculosis. Combinations of 7-methyljuglone with isoniazid or rifampicin resulted in a four to six-fold reduction in the minimum inhibitory concentration of each compound. Fractional inhibitory concentration (FIC) indexes obtained were 0.2 and 0.5, respectively, for rifampicin and isoniazid, suggesting a synergistic interaction between 7-methyljuglone and these anti-TB drugs. The ability of 7-methyljuglone to enhance the activity of isoniazid and rifampicin against both extracellular and intracellular organisms suggests that 7-methyljuglone may serve as a promising compound for development as an anti-tuberculous agent.

Topics: Antitubercular Agents; Cytotoxins; Drug Combinations; Ebenaceae; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Naphthoquinones; Plant Roots; Radiometry