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Chemical investigation of many bacterial and fungal, as well as plant species has revealed the presence of in-teresting compounds derived from naphthalene – 1,4-naphthoquinones and rarely also 1,2-naphthoquinones. They were detected in many species of families Bignoniaceae, Droseraceae, Plumbaginace, Boraginaceae, Juglandaceae as well as in species of small families, such as Dioncophyllaceae or Acanthaceae. Naphthoquinones have very interesting spectrum of biological actions, including antibiotic, antiviral, anti-inflammatory, antipyretic, antiproliferative and cytotoxic effects. Because of these properties the plants containing them are used in folk medicines, mainly by natives in Asia, where espe-cially Chinese medicine uses aerial as well as subterranean parts of these plants for hundreds years, and South America. The utilizing of naphthoquinones for medicinal purposes and their occurrence in nature is reviewed and discussed. Moreover, we review analytical techniques using for their analysis.
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... Quinones are highly reactive compounds of interest both in the mechanistic an applied fields [2,3]. For example, they can find application in natural and synthetic dye [4,5], and biopesticides and bioherbicides [6,7] and play important roles in man biochemical processes, being involved in cellular respiration [8,9], photosynthesis [10 and cellular defense [11,12]. In the pharmaceutical field, they are used as trypanocida anti-inflammatory [13], antithrombotic [14,15], antiviral [16], antifungal [17], an antitumor agents [18], but their clinical use as antineoplastic drugs [19] has been limite for a long time by their toxicity. ...
... Focusing attention on 1,4-naphthoquinone and some of its derivatives ( Quinones are highly reactive compounds of interest both in the mechanistic and applied fields [2,3]. For example, they can find application in natural and synthetic dyes [4,5], and biopesticides and bioherbicides [6,7] and play important roles in many biochemical processes, being involved in cellular respiration [8,9], photosynthesis [10], and cellular defense [11,12]. In the pharmaceutical field, they are used as trypanocidal, anti-inflammatory [13], antithrombotic [14,15], antiviral [16], antifungal [17], and antitumor agents [18], but their clinical use as antineoplastic drugs [19] has been limited for a long time by their toxicity. ...
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Article
A series of naphthoquinones, namely, 1,4-naphthoquinone, menadione, plumbagin, juglone, naphthazarin, and lawsone, were reacted with N-acetyl-L-cysteine, and except for lawsone, which did not react, the related adducts were obtained. After the tuning of the solvent and reaction conditions, the reaction products were isolated as almost pure from the complex reaction mixture via simple filtration and were fully characterized. Therefore, the aim of this work was to evaluate whether the antitumor activity of new compounds of 1,4-naphthoquinone derivatives leads to an increase in ROS in tumor cell lines of cervical carcinoma (HeLa), neuroblastoma (SH-SY5Y), and osteosarcoma (SaOS2, U2OS) and in normal dermal fibroblast (HDFa). The MTT assay was used to assay cell viability, the DCF-DA fluorescent probe to evaluate ROS induction, and cell-cycle analysis to measure the antiproliferative effect. Compounds 8, 9, and 12 showed a certain degree of cytotoxicity towards all the malignant cell lines tested, while compound 11 showed biological activity at higher IC50 values. Compounds 8 and 11 induced increases in ROS generation after 1 h of exposure, while after 48 h of treatment, only 8 induced an increase in ROS formation in HeLa cells. Cell-cycle analysis showed that compound 8 caused an increase in the number of G0/G1-phase cells in the HeLa experiment, while for the U2OS and SH-SY5Y cell lines, it led to an accumulation of S-phase cells. Therefore, these novel 1,4-naphthoquinone derivatives may be useful as antitumoral agents in the treatment of different cancers.
... Naphthoquinones have many physiological roles e.g. ubiquinone, plastoquinone and K vitamins are biochemical systems' functional ingredients [4][5][6]. They are usually yellow or brown in colour, and play important roles as dyes in pigmentation [4]. ...
... They are usually yellow or brown in colour, and play important roles as dyes in pigmentation [4]. Some of the naturally occurring naphthoquinones shows broad range of biological activities such as antimicrobial properties, cytotoxic and phytotoxic effects [6]. ...
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Expedient aqueous synthesis of 3,3-arylmethylenebis(2-hydroxy naphthalene-1,4-diones) by condensation reaction of aromatic aldehyde and 2-hydroxy-1,4-naphthoquinone under reflux and microwave irradiation using lemon juice as a catalyst has been studied. The green protocol described herein avoid severe reaction conditions and prove to be effective in terms of good yields, operational simplicity, easy work up and short reaction time. The antimicrobial properties of the synthesized compound can be explored and is expected to be comparable to parent compound Lawsone, which is known to impart red-orange colour.
... Thus, the fragment with m/z 261.007 is trimethylthiolated toluquinone (Figure 4A), where toluquinone has been shown to be produced by the decarboxylation of homogentisic acid. 33 These observations enable the proposition of the following biosynthetic scheme for production of 1 and inactivation of trimethoprim by B. cenocepacia ( Figure 5). Here, the G378R mutation in the HmgA enzyme leads to accumulation of homogentisic acid, which is oxidized to 1,4-benzoquinone. ...
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Opportunistic infections by Burkholderia cenocepacia are life threatening for patients suffering from cystic fibrosis and chronic granulomatous disease. These infections are often associated with variable clinical outcomes, prompting an interest in molecular investigations of phenotypes associated with disease severity. The production of the pyomelanin pigment is one such phenotype, which was recently linked to the ability of clinical strains to carry out biotransformation of the antibiotic trimethoprim. However, this biotransformation product was not identified, and differences in metabolite production associated with pyomelanin pigmentation are poorly understood. Here, we identify several key metabolites produced exclusively by the pyomelanin-producing strains. To provide insight into the structures and biosynthetic origin of these metabolites, we developed a mass spectrometry-based strategy coupling unsupervised in silico substructure prediction with stable isotope labeling referred to as MAS-SILAC (Metabolite Annotation assisted by Substructure discovery and Stable Isotope Labeling by Amino acids in Cell culture). This approach led to discovery of homogentisic acid as a precursor for biosynthesis of several natural products and for biotransformation of trimethoprim, representing a previously unknown mechanism of antibiotic tolerance. This work presents application of computational methods for analysis of untargeted metabolomic data to link the chemotype of pathogenic microorganisms with a specific phenotype. The observations made in this study provide insights into the clinical significance of the melanated phenotype.
... In line with these previous findings, the dry extract used within this study was pharmacologically active despite the absence of naphthoquinones [9], which have formerly often been regarded as the active principle in Drosera extracts and considered as marker compounds for quality control [28]. These findings are certainly favorable with respect to the general toxicity of this compound class [29,30]. ...
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Extracts from Drosera rotundifolia are traditionally used to treat cough symptoms during a common cold. The present study aimed to investigate the impact of extracts from D. rotundifolia and active compounds on the respiratory tract. Tracheal slices of C57BL/6N mice were used ex vivo to examine effects on airway smooth muscle (ASM) and ciliary beat frequency (CBF). Phosphodiesterase (PDE) inhibition assays were carried out to test whether PDE1 or PDE4 are targeted by the active compounds. An ethanol–water extract, as well as an aqueous fraction of this extract, exerted antispasmodic properties against acetylcholine-induced contractions. In addition, contractions induced by 60 mM K+ were abrogated by the aqueous fraction. Effects on ASM could be attributed to the flavonoids quercetin, 2″-O-galloylhyperoside and hyperoside. Moreover, the Drosera extract and the aqueous fraction increased the CBF of murine tracheal slices. Quercetin and 2″Ogalloylhyperoside were identified as active compounds involved in the elevation of CBF. Both compounds inhibited PDE1A and PDE4D. The elevation of CBF was mimicked by the subtypeselective PDE inhibitor rolipram (PDE4) and by 8methoxymethylIBMX. In summary, our study shows, for the first time, that a Drosera extract and its flavonoid compounds increase the CBF of murine airways while antispasmodic effects were transferred to ASM.
... Thus, the fragment with m/z 261.007 is trimethylthiolated toluquinone (Fig 4A), where toluquinone has been shown to be produced by the decarboxylation of homogentisic acid. 33 These observations enable the proposition of the following biosynthetic scheme for production of 1 and inactivation of trimethoprim by B. cenocepacia (Fig. 5). Here, the G378R mutation in the HmgA enzyme leads to accumulation of homogentisic acid, which is oxidized to 1,4-benzoquinone. ...
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Opportunistic infections by Burkholderia cenocepacia are life threatening for patients suffering from cystic fibrosis and chronic granulomatous disease. These infections are often associated with variable clinical outcomes, prompting an interest into molecular investigations of phenotypes associated with disease severity. The production of the pyomelanin pigment is one such phenotype, which was recently linked to the ability of clinical strains to carry out biotransformation of the antibiotic trimethoprim. However, this biotransformation product was not identified, and differences in metabolite production associated with pyomelanin pigmentation are poorly understood. Here, we identify several key metabolites produced exclusively by the pyomelanin-producing strains. To provide insight into the structures and biosynthetic origin of these metabolites, we developed a mass spectrometry-based strategy coupling unsupervised in silico substructure prediction with stable isotope labeling referred to as MAS-SILAC (Metabolite Annotation assisted by Substructure discovery and Stable Isotope Labeling by Amino acids in Cell culture). This approach led to discovery of homogentisic acid as a precursor for biosynthesis of several natural products and for biotransformation of trimethoprim, representing a previously unknown mechanism of antibiotic tolerance. This work presents application of computational methods for analysis of untargeted metabolomic data to link the chemotype of pathogenic microorganisms with a specific phenotype. The observations made in this study provide insights into the clinical significance of the melanated phenotype.
... Additionally, the currently existing chemotherapeutic agents are not suitable due to administration schedules, more cytotoxic effects, and their problem of drug resistance [43]. Thus, high therapeutic potential drug compound with an economically viable and non-toxic compound is the need of the hour that affect the metabolic pathways essential for the survival of parasite and help to combat animal trypanosomosis [44,45]. Muscle weakness, increased heart rate, salivation and diarrhoea. ...
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Naphthoquinone is a heterocyclic moiety whose natural derivatives are present as bioactive compounds in many plants and have stimulated a resurgence of interest in the past decades due to their wide range of pharmacological activities. Naphthoquinone agents have dynamic pharmacophore and privileged sub-structures in the chemistry of medicine. They have received much interest in drug discovery as trypanocidal because naphthoquinone and their derivatives revealed massive significance potential against the trypanosomes. Among natural naphthoquinones, lapachol, β-lapachone and its α-isomer exhibited useful trypanocidal activities. Some naphthoquinones have already been used commercially as an antiparasitic agent. Several naphthoquinones with diverse structural motifs have been synthesized and evaluated mainly against Trypanosoma cruzi and some studies have also been reported against Trypanosoma brucei and Trypanosoma evansi. This review summarized various mechanisms of action of naphthoquinone like reductive activation of quinone by the production of the semiquinone, generation of reactive oxygen species and free radicals such as superoxide anion radical and H2O2, and oxidative stress in the parasite. The information assembled in this review will help to understand the mechanism behind the activity and may also be useful to find the bio-efficacy of naphthoquinone compounds upon substitution against trypanosomatids.
... Naphthoquinones are considered as fortunate structures in the field of medicinal chemistry owing to their different biological potentials and structural properties. They are found in many higher plant families such as Avicenniaceae, Bignoniaceae, Boraginaceae, Droseraceae, Ebenaceae, Juglandaceae, Nepenthaceae, and Plumbagnaceae (Babula et al., 2009;López López et al., 2014;Vaverkova et al., 2014). They are the natural secondary metabolites of some fungi, algae, lichens, and actinomycetes (Basnet et al., 2019;Medentsev et al., 2005;Zhang et al., 2004). ...
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Over the past decades, a number of 1,4‐naphthoquinones have been isolated from natural resources and several of naphthoquinone derivatives with diverse structural motif have been synthesized; they possess a multitude of biochemical properties and modulate numerous pharmacological roles that offer new targets for addressing the challenges pertaining to novel drug developments. Among natural naphthoquinones, lapachol, α‐ lapachone, β‐lapachone, lawsone, juglone, and plumbagin have been evaluated for its potential as antitrypanosomal activities. The chemotherapeutic drugs available for combating human trypanosomiasis i.e., American trypanosomiasis and African trypanosomiasis caused by Trypanosoma cruzi and Trypanosoma brucei, respectively; and animal tripanosomosis caused by Trypanosoma evansi have a problem of drug resistance and several toxic effect. Therefore, search of alternative effective drug molecules, without toxic effects, have enthused the researchers for searching new drug entity with potential clinical efficacy. In the search for new antitrypanosomal compound, this review focuses on different natural quinones and their synthetic derivatives associated with antitrypanosomal studies. In this context, this review will be useful for the development of new antitrypanosomal drugs mainly based on different structural modification of natural as well as synthetic naphthoquinones. Naphthoquinones molecules such as 1,4‐naphthoquinone, lapachol, lawsone, juglon, plumbagin and their derivative are the promising ‘lead’ class from diverse medicinal chemistry owing to their activity for the treatment of several disease and trypanocidal activity is one by generating more reactive oxygen species and oxidative stress in the parasite and responsible for parasite death.
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