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Angewandte Chemie (International Ed. in... Mar 2021Sulfur incorporation into natural products is a critical area of biosynthetic studies. Recently, a subset of sulfur-containing angucyclines has been discovered, and yet,...
Sulfur incorporation into natural products is a critical area of biosynthetic studies. Recently, a subset of sulfur-containing angucyclines has been discovered, and yet, the sulfur incorporation step is poorly understood. In this work, a series of thioether-bridged angucyclines were discovered, and a cryptic epoxide Michael acceptor intermediate was revealed en route to thioangucyclines (TACs) A and B. However, systematic gene deletion of the biosynthetic gene cluster (BGC) by CRISPR/Cas9 could not identify any gene responsible for the conversion of the epoxide intermediate to TACs. Instead, a series of in vitro and in vivo experiments conclusively showed that the conversion is the result of two non-enzymatic steps, possibly mediated by endogenous hydrogen sulfide. Therefore, the TACs are proposed to derive from a detoxification process. These results are expected to contribute to the study of both angucyclines and the utilization of inorganic sulfur in natural product biosynthesis.
Topics: Anthraquinones; Molecular Conformation; Sulfhydryl Compounds; Sulfur
PubMed: 33465268
DOI: 10.1002/anie.202015570 -
Journal of Natural Products Oct 2023The photoantimicrobial potential of four mushroom species (i.e., , , , and ) was explored by studying the minimal inhibitory concentrations (MIC) via a light-modified...
The photoantimicrobial potential of four mushroom species (i.e., , , , and ) was explored by studying the minimal inhibitory concentrations (MIC) via a light-modified broth microdilution assay based on the recommended protocols of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The extracts were tested against , , and under blue (λ = 428 and 478 nm, = 30 J/cm) and green light (λ = 528 nm, = 30 J/cm) irradiation. Three extracts showed significant photoantimicrobial effects at concentrations below 25 μg/mL. Targeted isolation of the major pigments from led to the identification of two new potent photoantimicrobials, one of them (i.e., dermocybin) being active against and under green light irradiation [PhotoMIC = 39.5 μM (12.5 μg/mL) and 2.4 μM (0.75 μg/mL), respectively] and the other one (i.e., emodin) being in addition active against in a low micromolar range [PhotoMIC = 11.1 μM (3 μg/mL)]. Intriguingly, dermocybin was not (photo)cytotoxic against the three tested cell lines, adding an additional level of selectivity. Since both photoantimicrobials are not charged, this discovery shifts the paradigm of cationic photosensitizers.
Topics: Antifungal Agents; Photosensitizing Agents; Escherichia coli; Staphylococcus aureus; Candida albicans; Anthraquinones; Microbial Sensitivity Tests
PubMed: 37708055
DOI: 10.1021/acs.jnatprod.2c01157 -
Phytochemistry Jun 2021Ten undescribed anthranoids, including three anthraquinone acetals as racemic mixtures, (±)-kenganthranol G-I, and seven prenylated anthranols, (±)-kenganthranol J-M...
Ten undescribed anthranoids, including three anthraquinone acetals as racemic mixtures, (±)-kenganthranol G-I, and seven prenylated anthranols, (±)-kenganthranol J-M and harunganol G-I, together with thirteen known compounds, were isolated from the stem bark of Harungana madagascariensis. The structures of (±)-kenganthranol G and (±)-kenganthranol J were confirmed by X-ray crystallography. (±)-Kenganthranol G was separated into (+)-kenganthranol G and (-)-kenganthranol G by chiral HPLC and their absolute configurations were established by electronic circular dichroism. (±)-Kenganthranol L displayed α-glucosidase inhibitory activity with an IC of 4.4 μM.
Topics: Anthraquinones; Clusiaceae; Molecular Structure
PubMed: 33711738
DOI: 10.1016/j.phytochem.2021.112711 -
International Journal of Molecular... Oct 2023Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects... (Review)
Review
Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects resulting from the use of standard chemotherapeutic drugs, as well as the phenomenon of multidrug resistance (MDR), limit the effectiveness of approved therapies. Advanced research in the BC area is necessary to create more effective and safer forms of therapy to improve the outlook for individuals diagnosed with this aggressive neoplasm. For decades, plants and natural products with anticancer properties have been successfully utilized in treating various medical conditions. Anthraquinone derivatives are tricyclic secondary metabolites of natural origin that have been identified in plants, lichens, and fungi. They represent a few botanical families, e.g., Rhamnaceae, Rubiaceae, Fabaceae, Polygonaceae, and others. The review comprehensively covers and analyzes the most recent advances in the anticancer activity of 1,8-dihydroanthraquinone derivatives (emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion) applied both individually, or in combination with other chemotherapeutic agents, in in vitro and in vivo BC models. The application of nanoparticles for in vitro and in vivo evidence in the context of 1,8-dihydroanthraquinone derivatives was also described.
Topics: Humans; Female; Emodin; Breast Neoplasms; Rheum; Anthraquinones; Plant Extracts; Polygonaceae
PubMed: 37958772
DOI: 10.3390/ijms242115789 -
Bioorganic & Medicinal Chemistry Oct 2019In order to overcome therapy resistance in cancer, scientists search in nature for novel lead structures for the development of improved chemotherapeutics.... (Review)
Review
In order to overcome therapy resistance in cancer, scientists search in nature for novel lead structures for the development of improved chemotherapeutics. Anthraquinones belong to a class of tricyclic organic natural compounds with promising anti-cancer effects. Anthraquinone derivatives are rich in structural diversity, and exhibit pleiotropic properties, among which the modulation of autophagy seems promising in the context of overcoming cancer-therapy resistance. Among the most promising derivatives in this regard are emodin, aloe emodin, rhein, physcion, chrysophanol and altersolanol A. On the molecular level, these compounds target autophagy via different upstream pathways including the AKT/mTOR-axis and transcription of autophagy-related proteins. The role of autophagy is pro-survival as well as cell death-promoting, depending on derivatives and their cell type specificity. This review summarizes observed effects of anthraquinone derivatives on autophagy and discusses targeted pathways and crosstalks. A cumulative knowledge about this topic paves the way for further research on modes of action, and aids to find a therapeutic window of anthraquinones in cancer-therapy.
Topics: Animals; Anthraquinones; Antineoplastic Agents; Autophagy; Cell Death; Dose-Response Relationship, Drug; Humans; Molecular Structure; Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Structure-Activity Relationship; TOR Serine-Threonine Kinases
PubMed: 31420258
DOI: 10.1016/j.bmc.2019.115042 -
Fitoterapia Mar 2023Emodin is the main pharmacodynamic components of rhubarb, with significant pharmacological effects and clinical efficacy.Emodin has a variety of therapy effects, such as... (Review)
Review
Emodin is the main pharmacodynamic components of rhubarb, with significant pharmacological effects and clinical efficacy.Emodin has a variety of therapy effects, such as anti-cancer, anti-fibrosis effects, and is widely used to treat encephalitis, diabetic cataract and organ fibrosis. Several studies have shown that emodin has a good treatment effect on organ fibrosis, but the mechanism is complex. Moreover, the evidence of some studies is conflicting and confusing. This paper reviewed the mechanism, pharmacokinetics and toxicology of emodin in fibrosis treatment, and briefly discussed relevant cutting-edge new formulations to improve the efficacy, the result can provide some reference for future study.
Topics: Rats; Animals; Emodin; Anthraquinones; Rats, Sprague-Dawley; Molecular Structure; Plant Extracts; Rheum
PubMed: 36436587
DOI: 10.1016/j.fitote.2022.105358 -
Bioorganic Chemistry Feb 2021We report the design, synthesis, and biological evaluation of 13 new and 1 known anthraquinone derivatives which exerted cytotoxicity against PC3, A549 and NTUB1 cell...
We report the design, synthesis, and biological evaluation of 13 new and 1 known anthraquinone derivatives which exerted cytotoxicity against PC3, A549 and NTUB1 cell lines. The results indicate that, among these 14, compounds-1 and 14 showed the highest growth inhibitory effect on NTUB1 and PC3 cells, respectively. Compound-1 at lower doses targets DNA, induces DNA damage and subsequently triggers G2/M arrest and apoptotic cell death at 24 h. Previously we reported that 14 induced PC3 cell autophagy and in treated PC3 cells, cleaved caspase-3 and cleaved PARP, and survivin did not increase and increase, respectively. The autophagic and necrotic cell deaths mediated by 14-triggered ROS generation. Our study is the first to investigate the biological mechanism of 14 action in detail. We find that when 14 was co-administrated with Bafilomycin A1 (BAF) in PC3 cells, rapid necrotic cell death occurred with no cleaved caspase-3 and cleaved PARP activation and increasing the expression of survivin. We further show that necrotic signaling in these cells coincided with production of reactive oxygen species. In the present study, we developed methods to synthesize five new 14 analogues for studing the structure-activity relationships. This study could provide valuable sight to find new antitumor agents for cancer therapy.
Topics: Anthraquinones; Antineoplastic Agents; Apoptosis; Autophagy; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA Damage; Drug Design; Drug Screening Assays, Antitumor; G2 Phase Cell Cycle Checkpoints; Humans; Molecular Structure; Reactive Oxygen Species; Structure-Activity Relationship
PubMed: 33384144
DOI: 10.1016/j.bioorg.2020.104395 -
Bioorganic & Medicinal Chemistry Jan 2022Inhibitors of the monoamine oxidase (MAO) enzymes are important agents for the treatment of central nervous system disorders and have established roles in the therapy of...
Inhibitors of the monoamine oxidase (MAO) enzymes are important agents for the treatment of central nervous system disorders and have established roles in the therapy of neuropsychiatric diseases such as depression and in the neurodegenerative disorder, Parkinson's disease. A number of good potency MAO inhibitors consist of tricyclic ring systems as exemplified by the structures of harmine and the phenothiazine compound methylene blue. In an attempt to discover novel MAO inhibitors, 30 phenothiazine, anthraquinone and related tricyclic derivatives were selected and evaluated as potential inhibitors of human MAO-A and MAO-B. The results show that, in general, the tricyclic compounds are specific inhibitors of MAO-A over the MAO-B isoform. Quinizarin (IC = 0.065 µM), 2-chloro-7-methoxy-10H-phenothiazine (IC = 0.576 µM) and xanthone (IC = 0.623 µM) proved to be the most potent MAO-A inhibitors, while the most potent MAO-B inhibition was recorded with 2-chloro-7-methoxy-10H-phenothiazine (IC = 1.34 µM), 1,2-diaminoanthraquinone (IC = 2.41 µM) and emodin (IC = 3.24 µM). These compounds may undergo further preclinical evaluation and development, and may also serve as potential lead compounds for the future design of MAO inhibitors.
Topics: Anthraquinones; Dose-Response Relationship, Drug; Humans; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Phenothiazines; Structure-Activity Relationship
PubMed: 34915314
DOI: 10.1016/j.bmc.2021.116558 -
Current Drug Targets 2021Nature has provided prodigious reservoirs of pharmacologically active compounds for drug development since times. Physcion and physcion 8-O-β-D-glucopyranoside (PG) are... (Review)
Review
Nature has provided prodigious reservoirs of pharmacologically active compounds for drug development since times. Physcion and physcion 8-O-β-D-glucopyranoside (PG) are bioactive natural anthraquinones which exert anti-inflammatory and anticancer properties with minimum or no adverse effects. Moreover, physcion also exhibits anti-microbial and hepatoprotective properties, while PG is known to have anti-sepsis as well as ameliorative activities against dementia. This review aims to highlight the natural sources and anticancer activities of physcion and PG, along with associated mechanisms of actions. On the basis of the literature, physcion and PG regulate multitudinous cell signaling pathways through the modulation of various regulators of cell cycle, protein kinases, microRNAs, transcriptional factors, and apoptosis linked proteins resulting in the effective killing of cancerous cells in vitro as well as in vivo. Both compounds effectively suppress metastasis, furthermore, physcion acts as an inhibitor of 6PGD and also plays an important role in chemosensitization. This review article suggests that physcion and PG are potent anticancer drug candidates, but further investigations on their mechanism of action and pre-clinical trials are mandatory in order to comprehend the full potential of these natural cancer killers in anticancer remedies.
Topics: Antineoplastic Agents; Emodin; Glucosides; Humans; Neoplasms; Signal Transduction
PubMed: 33050858
DOI: 10.2174/1389450121999201013154542 -
Molecules (Basel, Switzerland) Mar 2023The composition of an ethanol extract from the roots of Losinsk of the Trans-Ili Alatau wild flora was studied in order to determine its antiulcer activity. The...
The composition of an ethanol extract from the roots of Losinsk of the Trans-Ili Alatau wild flora was studied in order to determine its antiulcer activity. The phytochemical composition of the anthraquinone-flavonoid complex from (AFC) revealed the presence of numerous polyphenolic compounds, the most abundant of which are anthraquinones (1.77%), flavonoids (6.95%), and tannins (13.39%). The use of column chromatography (CC) and thin-layer chromatography (TLC) in conjunction with UV, IR, NMR spectroscopy, and mass spectrometry data allowed the researchers to isolate and identify the major components of the anthraquinone-flavonoid complex's polyphenol fraction: physcion, chrysophanol, emodin, isorhamnetin, quercetin, and myricetin. The gastroprotective effect of the polyphenolic fraction of the anthraquinone-flavonoid complex (AFC) of roots was examined in an experimental model of rat gastric ulcer induced by indomethacin. The preventive and therapeutic effect of the anthraquinone-flavonoid complex at a dose of 100 mg/kg was analyzed using intragastric administration per day for 1 to 10 days, followed by a histological examination of stomach tissues. It has been demonstrated that prophylactic and prolonged use of the AFC in laboratory animals resulted in significantly less pronounced hemodynamic and desquamative changes in the epithelium of gastric tissues. The acquired results thus offer fresh insight into the anthraquinone and flavonoid metabolite component composition of roots, and they imply that the examined extract can be used to develop herbal medicines with antiulcer activity.
Topics: Rats; Animals; Rumex; Anthraquinones; Plant Extracts; Flavonoids; Anti-Ulcer Agents; Stomach Ulcer
PubMed: 36903594
DOI: 10.3390/molecules28052347