-
Molecules (Basel, Switzerland) Aug 2022In recent decades, molecular hybridization has proven to be an efficient tool for obtaining new synthetic molecules to treat different diseases. Based on the core idea... (Review)
Review
In recent decades, molecular hybridization has proven to be an efficient tool for obtaining new synthetic molecules to treat different diseases. Based on the core idea of covalently combining at least two pharmacophore fragments present in different drugs and/or bioactive molecules, the new hybrids have shown advantages when compared with the compounds of origin. Hybridization could be successfully applied to anticancer drug discovery, where efforts are underway to develop novel therapeutics which are safer and more effective than those currently in use. Molecules presenting naphthoquinone moieties are involved in redox processes and in other molecular mechanisms affecting cancer cells. Naphthoquinones have been shown to inhibit cancer cell growth and are considered privileged structures and useful templates in the design of hybrids. The present work aims at summarizing the current knowledge on antitumor hybrids built using 1,4- and 1,2-naphthoquinone (present in natural compounds as lawsone, napabucasin, plumbagin, lapachol, α-lapachone, and β -lapachone), and the related quinolone- and isoquinolinedione scaffolds reported in the literature up to 2021. In detail, the design and synthetic approaches adopted to produce the reported compounds are highlighted, the structural fragments considered in hybridization and their biological activities are described, and the structure-activity relationships and the computational analyses applied are underlined.
Topics: Antineoplastic Agents; Cell Line, Tumor; Naphthoquinones; Structure-Activity Relationship
PubMed: 35956896
DOI: 10.3390/molecules27154948 -
Chemical & Pharmaceutical Bulletin 2020Over the past decade, a number of new 1,4-naphthoquinones have been isolated from natural sources and new 1,4-naphthoquinones with diverse structural features have been... (Review)
Review
Over the past decade, a number of new 1,4-naphthoquinones have been isolated from natural sources and new 1,4-naphthoquinones with diverse structural features have been synthesized. Cardioprotective, anti-ischemic, hepatoprotective, neuroprotective and some other new properties were found for these compounds; their role in protecting against neurodegenerative diseases has been established. Their anti-inflammatory, antimicrobial and antitumor activities have been studied in more detail; new, previously unknown intracellular molecular targets and mechanisms of action have been discovered. Some compounds of this class are already being used as a medicinal drugs and some substances can be used as biochemical tools and probes for non-invasive detection of pathological areas in cells and tissues in myocardial infarction and neurodegenerative diseases using modern molecular imaging techniques.
Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Bacteria; Cytokines; Humans; Leukocytes, Mononuclear; Naphthoquinones; Oxidative Stress; Protective Agents; Trypanosoma
PubMed: 31902901
DOI: 10.1248/cpb.c19-00911 -
Marine Drugs Jul 2021The marine drug histochrome is a special natural antioxidant. The active substance of the drug is echinochrome A (Ech A,... (Review)
Review
The marine drug histochrome is a special natural antioxidant. The active substance of the drug is echinochrome A (Ech A, 7-ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone), the most abundant quinonoid pigment in sea urchins. The medicine is clinically used in cardiology and ophthalmology based on the unique properties of Ech A, which simultaneously block various links of free radical reactions. In the last decade, numerous studies have demonstrated the effectiveness of histochrome in various disease models without adverse effects. Here, we review the data on the various clinical effects and modes of action of Ech A in ophthalmic, cardiovascular, cerebrovascular, inflammatory, metabolic, and malignant diseases.
Topics: Antioxidants; Aquatic Organisms; Humans; Naphthoquinones
PubMed: 34436251
DOI: 10.3390/md19080412 -
Arhiv Za Higijenu Rada I Toksikologiju Mar 2020Despite its evidenced beneficial herbicidal, antibacterial, antiviral, antifungal, and antioxidant effects, the application of juglone (5-hydroxy-1,4,-naphthoquinone) is... (Comparative Study)
Comparative Study
Despite its evidenced beneficial herbicidal, antibacterial, antiviral, antifungal, and antioxidant effects, the application of juglone (5-hydroxy-1,4,-naphthoquinone) is limited due to its low water solubility and allelopathic and toxic effects. In recent years, research has aimed to overcome these limitations by increasing its solubility and controlling its release through nanoparticular systems. This is the first study to have synthesised and characterised juglone-loaded polymeric nanoparticles and compared them with free juglone for cytotoxicity in mouse (L929 fibroblasts) and alfalfa cells and for mutagenic potential in Salmonella typhimurium TA98/100. Mouse and plant cells treated with free and nano-encapsulated juglone showed a decrease in cell viability in a dose and time-dependent manner, but this effect was significantly lower with the nano-encapsulated form at lower doses. In the TA98 strain with S9, nano-encapsulated juglone did not exhibit mutagenic effects, unlike the free form. Since all results show that juglone encapsulation with polymeric nanoparticles reduced the toxic and mutagenic effects, it has a promising potential to be applied in medicine, food safety, and agriculture.
Topics: Animals; Cell Survival; Cytotoxins; Fibroblasts; Medicago sativa; Mice; Mutagens; Naphthoquinones; Solubility
PubMed: 32597139
DOI: 10.2478/aiht-2020-71-3344 -
European Journal of Medicinal Chemistry Mar 2024Cancer encompasses a group of pathologies with common characteristics, high incidence, and prevalence in all countries. Although there are treatments available for this... (Review)
Review
Cancer encompasses a group of pathologies with common characteristics, high incidence, and prevalence in all countries. Although there are treatments available for this disease, they are not always effective or safe, often failing to achieve the desired results. This is why it is necessary to continue the search for new therapies. One of the strategies for obtaining new antitumor drugs is the use of 1,4-naphthoquinone as a scaffold in synthetic or natural products with antitumor activity. This review focuses on compiling studies related to the antitumor activity of 1,4-naphthoquinone and its natural and synthetic derivatives over the last 10 years. The work describes the main natural naphthoquinones with antitumor activity and classifies the synthetic naphthoquinones based on the structural modifications made to the scaffold. Additionally, the formation of metal complexes using naphthoquinones as a ligand is considered. After a thorough review, 197 synthetic compounds with potent biological activity against cancer have been classified according to their chemical structures and their mechanisms of action have been described.
Topics: Cell Line, Tumor; Naphthoquinones; Antineoplastic Agents; Biological Products
PubMed: 38458106
DOI: 10.1016/j.ejmech.2024.116249 -
Biological Chemistry Jan 2022Bone metabolism is essential for maintaining bone mineral density and bone strength through a balance between bone formation and bone resorption. Bone formation is... (Review)
Review
Bone metabolism is essential for maintaining bone mineral density and bone strength through a balance between bone formation and bone resorption. Bone formation is associated with osteoblast activity whereas bone resorption is linked to osteoclast differentiation. Osteoblast progenitors give rise to the formation of mature osteoblasts whereas monocytes are the precursors for multi-nucleated osteoclasts. Chronic inflammation, auto-inflammation, hormonal changes or adiposity have the potential to disturb the balance between bone formation and bone loss. Several plant-derived components are described to modulate bone metabolism and alleviate osteoporosis by enhancing bone formation and inhibiting bone resorption. The plant-derived naphthoquinone plumbagin is a bioactive compound that can be isolated from the roots of the genus. It has been used as traditional medicine for treating infectious diseases, rheumatoid arthritis and dermatological diseases. Reportedly, plumbagin exerts its biological activities primarily through induction of reactive oxygen species and triggers osteoblast-mediated bone formation. It is plausible that plumbagin's reciprocal actions - inhibiting or inducing death in osteoclasts but promoting survival or growth of osteoblasts - are a function of the synergy with bone-metabolizing hormones calcitonin, Parathormone and vitamin D. Herein, we develop a framework for plausible molecular of plumbagin in bone metabolism.
Topics: Bone Resorption; Cell Differentiation; Humans; Inflammation; Naphthoquinones; Osteoblasts; Osteoclasts; Phytochemicals
PubMed: 34882360
DOI: 10.1515/hsz-2021-0290 -
African Health Sciences Mar 2014Naphthoquinone is a class of phenolic compounds derived from naphthalene. 7-Methyljuglone (7-MJ) is a naphthoquinone also known as ramentaceone or... (Review)
Review
BACKGROUND
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.
OBJECTIVES
This review was aimed at providing available chemically and pharmacological data on 7-MJ.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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
PubMed: 26060480
DOI: 10.4314/ahs.v14i1.31 -
Biomolecules Aug 2020Naphthoquinone-based meroterpenoids are hybrid polyketide-terpenoid natural products with chemical diversity and a broad range of biological activities. Here, we report...
Naphthoquinone-based meroterpenoids are hybrid polyketide-terpenoid natural products with chemical diversity and a broad range of biological activities. Here, we report the isolation of a group of naphthoquinone-containing compounds from sp. B9173, and their structures were elucidated by using a combination of spectroscopic techniques, including 1D, 2D NMR, and high-resolution mass (HRMS) analysis. Seven flaviogeranin congeners or intermediates, three of which were new, have been derived from common naphthoquinone backbone and subsequent oxidation, methylation, prenylation, and amino group incorporation. Both flaviogeranin B1 () and B () contain an amino group which was incorporated into the C8 of 1,3,6,8-terhydroxynaphthalene (THN). Flaviogeranin D () contains an intact -geranylgeranyl residue attached to the C2 of THN, while the -geranylgeranyl group of links with the hydroxyl on the C2 site of THN. Four compounds were selected and tested for antibacterial activity and cytotoxicity, with and flaviogeranin C2 () displaying potent activity against selected bacteria and cancer cell lines. In light of the structure features of isolated compounds and the biosynthetic genes, a biosynthetic pathway of naphthoquinone-based flaviogeranins has been proposed. These isolated compounds not only extend the structural diversity but also represent new insights into the biosynthesis of naphthoquinone-based meroterpenoids.
Topics: A549 Cells; Anti-Bacterial Agents; Antineoplastic Agents; Aquatic Organisms; Biological Products; Biosynthetic Pathways; Cell Proliferation; Cell Survival; HeLa Cells; Humans; Microbial Sensitivity Tests; Molecular Structure; Naphthoquinones; Streptomyces; Terpenes
PubMed: 32824158
DOI: 10.3390/biom10081187 -
Synthesis of Naphthoquinone Derivatives: Menaquinones, Lipoquinones and Other Vitamin K Derivatives.Molecules (Basel, Switzerland) Sep 2020Menaquinones are a class of isoprenoid molecules that have important roles in human biology and bacterial electron transport, and multiple methods have been developed... (Review)
Review
Menaquinones are a class of isoprenoid molecules that have important roles in human biology and bacterial electron transport, and multiple methods have been developed for their synthesis. These compounds consist of a methylnaphthoquinone (MK) unit and an isoprene side chain, such as found in vitamin K (phylloquinone), K, and other lipoquinones. The most common naturally occurring menaquinones contain multiple isoprene units and are very hydrophobic, rendering it difficult to evaluate the biological activity of these compounds in aqueous assays. One way to overcome this challenge has been the application of truncated MK-derivatives for their moderate solubility in water. The synthesis of such derivatives has been dominated by Friedel-Crafts alkylation with BF∙OEt. This attractive method occurs over two steps from commercially available starting materials, but it generally produces low yields and a mixture of isomers. In this review, we summarize reported syntheses of both truncated and naturally occurring MK-derivatives that encompass five different synthetic strategies: Nucleophilic ring methods, metal-mediated reactions, electrophilic ring methods, pericyclic reactions, and homologation and side chain extensions. The advantages and disadvantages of each method are discussed, identifying methods with a focus on high yields, regioselectivity, and stereochemistry leading to a detailed overview of the reported chemistry available for preparation of these compounds.
Topics: Alkylation; Catalysis; Naphthoquinones; Oxidation-Reduction; Vitamin K; Vitamin K 2
PubMed: 33003459
DOI: 10.3390/molecules25194477 -
MBio Feb 2020Despite the important biological activities of natural product naphthoquinones, the biosynthetic pathways of and resistance mechanisms against such compounds remain...
Despite the important biological activities of natural product naphthoquinones, the biosynthetic pathways of and resistance mechanisms against such compounds remain poorly understood in fungi. Here, we report that the genes responsible for the biosynthesis of naphthoquinones (monasones) reside within the gene cluster for azaphilone pigments (MonAzPs). We elucidate the biosynthetic pathway of monasones by a combination of comparative genome analysis, gene knockouts, heterologous coexpression, and and enzymatic reactions to show that this pathway branches from the first polyketide intermediate of MonAzPs. Furthermore, we propose that the monasone subset of biosynthetic genes also encodes a two-tiered resistance strategy in which an inducible monasone-specific exporter expels monasones from the mycelia, while residual intracellular monasones may be rendered nontoxic through a multistep reduction cascade. The genes for naphthoquinone (monasone) biosynthesis are embedded in and form a composite supercluster with the azaphilone pigment biosynthetic gene cluster. Early biosynthetic intermediates are shared by the two pathways. Some enzymes encoded by the supercluster play double duty in contributing to both pathways, while others are specific for one or the other pathway. The monasone subcluster is independently regulated and inducible by elicitation with competing microorganisms. This study illustrates genomic and biosynthetic parsimony in fungi and proposes a potential path for the evolution of the mosaic-like azaphilone-naphthoquinone supercluster. The monasone subcluster also encodes a two-tiered self-resistance mechanism that models resistance determinants that may transfer to target microorganisms or emerge in cancer cells in case of naphthoquinone-type cytotoxic agents.
Topics: Biosynthetic Pathways; Drug Resistance, Fungal; Monascus; Multigene Family; Naphthoquinones
PubMed: 32019788
DOI: 10.1128/mBio.02676-19