ArticlePDF Available

Abstract and Figures

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.
Content may be subject to copyright.
A preview of the PDF is not available
... 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. ...
Article
Full-text available
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]. ...
Article
Full-text available
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.
... Additionally, fungal endophytes residing in rare or endangered plants, rare ecological niches and extreme habitats have high economic value instead of the rich and diverse reserve of novel bioactive compounds. Some of the important pigments from endophytic fungi (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) are listed in Table 1 and soil fungi (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49) in Table 2. The chemical structures of prominent pigments from endophytic and soil fungi are depicted in Supplementary Tables 1 and 2 respectively. ...
... All these compounds have been proven to possess anticancer effects (34). This revelation has led to the creation of novel anticancer Monascus-based pharmaceutical and food items to alleviate human malignancies (35). Penicillium sp. ...
Article
Full-text available
Concerns about the negative impacts of synthetic colorants on both consumers and the environment have sparked a surge of interest in natural colorants. This has boosted the global demand for natural colorants in the food, cosmetics and textile industries. Pigments and colorants derived from plants and microorganisms are currently the principal sources used by modern industry. When compared to the hazardous effects of synthetic dyes on human health, natural colors are quickly degradable and have no negative consequences. In fact, fungal pigments have multidimensional bioactivity spectra too. Western Ghats, a biodiversity hotspot has a lot of unique ecological niches known to harbor potential endophytic pigment-producing fungi having enumerable industrial and medical applications. Most of the fungi have coevolved with the plants in a geographical niche and hence the endophytic associations can be thought to bring about many mutually beneficial traits. The current review aims to highlight the potential of fungal pigments found in the Western ghats of India depicting various methods of isolation and screening, pigment extraction and uses. There is an urgent need for bioprospecting for the identification and characterization of extremophilic endophytic fungi to meet industry demands and attain sustainability and balance in nature, especially from geographic hotspots like the Western Ghats.
... 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. ...
Preprint
Full-text available
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. ...
Article
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). ...
Article
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.
Article
The problem with contemporary drugs are that they dissipate to the whole body of the consumer and hence needs a larger amount; most of which are wasted or end in becoming harmful agents to some parts of the body. However, advent of modern technologies and applied science doesn’t make it that much tougher. As we speak, the drug designing science is moving forward tremendously to selective activation of drugs by cellular processes in tumor cells or by externally controlled activation. One of many approaches for classical and non-classical targets includes the use of metal complexes with bio-relevant conditions, i.e. the Ru and Pt based drugs in case of anti-tumor activities. Ru, being the newcomer in this field has some great advantages than contemporary Pt-based drugs. Compared to Pt- based drugs, the Ru compounds have novel mechanistic actions, potential of reduced toxicity, non-cross resistance and a different spectrum of activities. Here, in this review, we discussed about the recent and notable emergence of Ru-based drugs against cancer and its industrial utilization and market value, from historical context towards the future progress.
Article
Full-text available
One of the main hotspots in the global drug discovery endeavour is the microbial natural products due not only to their great structural diversity and complexity but also their capacity to generate new analogues by changing the culture conditions, thus providing them with a wide array of biological and pharmacological properties. Among microorganisms, fungi are considered one of the most prolific producers of bioactive natural products. Up to now, more than twenty thousand metabolites have been isolated from terrestrial and marine-derived fungi of different genera. Naturally occurring naphthoquinones and naphthalenones are a large group of secondary metabolites obtained from several sources including higher plants, fungi, and some bacteria, which showed a wide range of biological and pharmacological activities as well as biotechnological potentials. The present review discusses the chemical characteristics and biological/pharmacological activities of fungal naphthoquinones and naphthalenones reported over the period from 2000 to 2021, highlighting 153 naphthoquinones and their derivatives from twenty-six different fungal genera. Additionally, insights into their biogenesis are briefly discussed.
Article
Full-text available
1,2-Naphthoquinone (2-NQ) is a nucleophile acceptor that non-selectively makes covalent bonds with cys-teine residues in various cellular proteins, and is also found in diesel exhaust, an air pollutant. This molecule has rarely been considered as a pharmacophore of bioactive compounds, in contrast to 1,4-naphthoquinone. We herein designed and synthesized a compound named N-(7,8-dioxo-7,8-dihydronaphthalen-1-yl)-2-methoxybenzamide (MBNQ), in which 2-NQ was hybridized with the nuclear factor-κB (NF-κB) inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) as a nucleophile acceptor. Although 50 µM MBNQ did not inhibit NF-κB signaling, 10 µM MBNQ induced cell death in the lung cancer cell line A549, which was insensitive to 2-NQ (10 µM). In contrast, MBNQ was less toxic in normal lung cells than 2-NQ. A mechanistic study showed that MBNQ mainly induced apoptosis, presumably via the activation of p38 mitogen-activated protein kinase (MAPK). Collectively, the present results demonstrate that the introduction of an appropriate substituent into 2-NQ constitutes a new biologically active entity, which will lead to the development of 2-NQ-based drugs.
Article
Plants are rich in active compounds, which can have an effect on the growth of other plants. In this context, the present work aimed to evaluate the effect of dichloromethanolic extracts from fresh and dried plants of Dionaea muscipula and compare it with its major compound in Lactuca sativa and Allium cepa. For this end, we conducted biological assays, determining the effects on germination, early development and cell cycle in plantlets and meristematic cells of L. sativa and A. cepa. The major compound identified by GC-EM was plumbagin with 89.71% in fresh plants and 53.13% in dry plants. The growth curves revealed the concentrations of 305,5; 538,4 and 32,08 μg mL−1 for fresh, dried and plumbagin, respectively, as those reducing 50% of germination %. And A. cepa with IC50: 279,3; 552,7 and 11,68 μg mL−1, respectively. Treatment with both extracts affected seedling growth (root and shoot) similarly to glyphosate, but only in L. sativa. Glyphosate did not affect the growth of A. cepa, which was observed in the extracts and plumbagin. Extracts at 1600, 800, and 400 μg mL−1 proved to be good options for pre-emergence control, while concentrations of 800, 400, and 200 μg mL−1 caused cell-cycle changes that compromised seedling viability in late development. Chromosome stickiness was the most frequent and did not indicate the mechanism of genotoxicity of the extracts, but the high prevalence of condensed nuclei suggests that cytotoxicity occurred with the activation of apoptotic pathways, common to naphthoquinones. This suggests that D. muscipula extracts are toxic to plants due to the availability of plumbagin, and they have the potential of use, affecting from seed germination to the early development of L. sativa and A. cepa.
Article
Goniothalamus cheliensis Hu is a kind of plant of the genus Goniothalamus ( Annonaceae) distributing in Yunnan province, southwest of China. In order to seek for the new type of antitumour agent from the genus, we discovered that the EtOH extract of the roots of the titled plant showed strong cytotoxic activities against a number of human cancer cell lines in preliminary pharmacological screening. Bioassay - guided fractionation of the alcoholic extract resulted in the isolation of thirty - eight compounds, among them two compounds were identified as new structures by the spectral data and chemical evidence, which were named as gonioquinone and goniofufurone acetonide respectively.
Article
Reinvestigation of the root of Rhinacanthus nasutus afforded, in addition to rhinacanthin-A to -D reported previously, two new dimethyldihydropyranonaphthoquinone esters (5, 6) and eight new 2-hydroxy-1,4-naphthoquinone esters (7-14) were isolated, The stereochemistry of rhinacanthin-A was determined as the R configuration, Compounds rhinacanthin-G to -N, belong to a class of 2-hydroxy-3-(3-hydroxy-2,2-dimethylpropyl)-1,4-naphthoquinone esters, and so far have been isolated only in this plant, Their biosynthesis is also discussed.
Article
The electrochemical behavior of 5-hydroxy-, 2,3-dichloro- and 2-amino-3-chloro-1,4-naphthoquinone has been studied in acetonitrile containing TEAPC 0.1M as supporting electrolyte by cyclic voltammetry, chronoamperometry and chronopotentiometry at the surface of GC electrode. The cyclic voltammetry of these compounds at low scan rates exhibits two one-electron peaks due to the reversible charge transfers without a coupled chemical reaction. The charge transfer rate constant, K-S, and the charge transfer coefficient, alpha, for electrochemical process were also estimated. The diffusion coefficient value, D, for each compound in acetonitrile has also been determined using chronoamperometry and chronopotentiometry data.
Article
A method for the determination of Shikonin in Arnebia euchroma ( Royle) Johnst in two different batches by capillary electrophoresis with high frequency conductivity detection ( contactless conductivity detection) was established. The electrophoretic parameters, such as the variety and concentration of buffer solution, separation voltage etc. were studied. Shikonin in the samples was separated and detected in buffer of 1. 0 mmol/L boracic acid +3. 0 mmol/L triethylamine at 18. 0 kV of constant voltage. The linear relationship ranged from 10. 0 to 250 mg/L (r = 0. 9962), the limit of detection (LOD), reached 5. 0 mg/L (S/N = 3). The RSDs for both intra-day and inter-day were less than 4% and recoveries were 93. 9%-97. 4% and 93. 1%-101% suppository respectively at various spiked levels. This study provides a useful mediod for the determination of Shikonin in Arnebia euchroma ( Royle) Johnst. It can be used for the quality control of products due to its simplicity, rapidity and sensitivity.
Article
A novel compound, plumbocatechin A 1, was isolated from the whole plant of Ceratostigma minus. The structural elucidation of 1 was mainly achieved by 2D-NMR techniques.
Article
Drosera indica L. D. burmanii Vahl. are red listed medicinal insectivorous plants in Andhra Pradesh. Their population is dwindling due to various environmental factors, medicinal value is one. Extensive field surveys have been carried out during 2001-2003 and the causes for their depletion were recoded. Seeds collected were subjected to various treatments to observe the germination. The rate of germination was quite low and unpredictable. Scanning electron microscopy of the seeds indicated distinct sculpture for these two species. All the accessions of D. indica showed transversely hexagonal plates on the seed coat, whereas D. burmanii showed tetragonal elongated reticulate shaped seed coat ornamentation. Based on our investigation, conservation measures have been suggested to preserve these valuable species, failing which these species would soon vanish regionally.
Article
The stem bark part of the plant, Kigelia pinnata, was analyzed phytochemically and a compound was isolated from the petroleum ether extract. The compound was characterized, employing chemical and spectral methods, and found to be a β-sitosterol.
Article
Acaricidal effects of materials derived from Caesalpinia sappan heartwoods against Dermatophagoides farinae and D. pteronyssinus were assessed and compared with those evidenced by commercial benzyl benzoate and DEET. The observed responses varied according to dosage and mite species. The LD50 values of the methanol extracts derived from C sappan heartwoods were 6.13 and 5.44 μg/cm3 against D. farinae and D. pteronyssinus, respectively. Furthermore, the ethyl acetate fraction derived from the methanol extract was approximately 8.71 more toxic than DEET against D. farinae, and 4.73 times more toxic against D. pteronyssinus. The biologically active constituent from the ethyl acetate fraction of C sappan heartwood extract was purified via silica gel chromatography and high-performance liquid chromatography. The structure of the acaricidal component was analyzed by GC-MS, 1H-NMR, 13C-NMR, 1H-13C COSY-NMR, and DEPT-NMR spectroscopy, and identified as juglone (5-hydroxy-1,4-naphthoquinone). Based on the LD50 values of juglone and its derivatives, the most toxic compound against D. farinae was juglone (0.076 μg/cm3), followed by benzyl benzoate (9.143 μg/cm3) and 2-methyl-1,4-naphthoquinone (40.0 μg/cm3). These results indicate that the acaricidal activity of C sappan heartwoods is likely to be the result of the effects of juglone. Additionally, juglone treatment was shown to effect a change in the color of the cuticles of house dust mites, from colorless-transparent to dark brownish-black. Accordingly, as a naturally occurring acaricidal agent, C. sappan heartwood-derived juglone should prove to be quite useful as a potential control agent, lead compound, and house dust mite indicator.
Article
The electrochemical behaviour of 5-hydroxy-2-methyl-1,4- naphthoquinone (Plumbagin) has been studied in non-aqueous solvent by cyclic voltammetry, chronoamperometry and chronopotentiometry at the surface of Au, Pt and GC electrodes using TEAPC and TBAPC as supporting electrolytes. In aprotic solvent such as acetonitrile, plumbagin exhibits two one-electron peaks due to the reversible charge transfers without a coupled chemical reaction at the surface of each solid electrode. Whereas, in dichloromethane it shows two one-electron quasi- reversible peaks. In amphiprotic solvent such as methanol, plumbagin shows a two-electron quasi-reversible peak. The charge transfer rate constant, K 0, the charge transfer coefficient, α, for electrochemical process and the diffusion coefficient value, D, for plumbagin have also been estimated in each solvent.