Hydroxyanthraquinones Research Articles

Cassia angustifolia Vahl. Leaves: Determination of Total Phenolic and Sennoside Contents of Different Fractions in Comparison with Their α- Glucosidase and Tyrosinase Inhibitory Effects.

Cassia angustifolia Vahl. (Senna) is a medicinal plant containing anthraquinone compounds such as sennoside. Senna is primarily valued for its laxative properties. In Persian medicine, this plant has been also used to treat various disorders such as diabetes and skin hyperpigmentation. Previous studies have shown that different species of senna, such as C. articulata, C. alata, C. Siamea, C. Surattensis inhibit alpha-amylase and α-glucosidase enzymes. To the best of our knowledge, no previous evidence is available on tyrosinase and α-glucosidase inhibitory effects of the extract and different fractions of C. angustifolia leaves. The purpose of this study was to investigate the inhibitory effect of the methanol-water extract and different fractions (hexane, chloroform, ethyl acetate, and remaining crude extract) of senna against tyrosinase and α-glucosidase and to investigate their total phenolic and sennoside B contents. Our findings depicted that the methanol-water extract and fractions had no significant anti-tyrosinase activity; however, some fractions were active toward α-glucosidase. The hexane fraction and the remaining crude extract demonstrated the highest inhibition on α-glucosidase compared to acarbose (positive control). In addition, the ethyl acetate fraction contains high phenolic and hydroxy anthraquinone derivatives based on the amount of sennoside B contents equivalent to 382.25 μg/mL of gallic acid and 1.525% of sennoside B, respectively. Moreover, no correlation was observed between the phenolic and sennoside contents of different fractions and their α-glucosidase inhibitory effect. Considering the α-glucosidase inhibition results, the hexane fraction of C. angustifolia can be a valuable fraction for in vitro and in vivo antidiabetic studies as well as further phytochemical studies. Further studies to identify the active substances and the exact mechanism of the bioactive ingredients on the inhibitory effects of α-glucosidase can provide promising results in the future.

Thermodynamics, kinetics and structure-activity relationship of hydroxyanthraquinones scavenging free radicals

Hydroxyanthraquinones (HAQs) have a significant antioxidant activity. In this study, the thermodynamic parameters, frontier molecular orbitals, and dynamic process of HAQs scavenging free radicals were systematically evaluated by density functional theory, and the results were verified by in vitro experiments. The results indicated that, in gas and benzene systems, the hydrogen atom transfer (HAT) was the main mechanism in the antioxidant process of HAQs because the bond dissociation enthalpies were much lower than the ionization potentials (IPs) and proton affinities. The polarity of the solvent (ethanol and water) led to a significant decrease of IPs, and the single electron transfer followed by proton transfer mechanism was the main mechanism. Furthermore, polar solvents were more conducive to the antioxidant activity of HAQs than non-polar solvents. Moreover, the antioxidant activity of HAQs increased with the increase of the number of hydroxyl groups. However, in the non-polar system, α-OH of HAQs was more likely to form hydrogen bonds with neighboring carbonyl O atoms, reducing its contribution to the antioxidation. In the polar system, α-OH can enhance the electron-donating ability to increase the antioxidant capacity.

The impact of π-π stacking interactions on photo-physical properties of hydroxyanthraquinones

The impact of π-π stacking interactions on photo-physical properties of hydroxyanthraquinone (HA) has been investigated using the density functional (DFT) and time-dependent density functional theory (TD-DFT) calculations in the gas phase and solution media. The vertical transition is characterized with strong HOMO-LUMO transition in the complexes. The intramolecular hydrogen bond (IHB) made in the HA and π-π complexes is strengthened after S0 → S1 excitation, such that the proton transfers is facilitated in the first excited state. The complexes exhibit an exothermic excited state intramolecular proton transfer (ESIPT) in the solution media, which is a barrierless process for some complexes. The π-π stacking interaction affects the absorption and emission bands of HA, and provides a large Stokes shift. This indicates the desirable fluorescence properties of π-π complexes, which are cross-validated by geometries, potential energy curve scannings, electronic and vibrational spectra, and frontier molecular orbital analyses.

Comparison of semi‐empirical and density functional approaches for the colour and constitution of anthraquinone dyes using X‐ray structure

AbstractTheoretical calculations with density functional theory, semi‐empirical PM5 random phase approximation and Zerner's intermediate neglect of differential overlap CI were carried out for various amino and hydroxy anthraquinones using X‐ray structure data. Comparing quantum chemical calculation results based on X‐ray structure, the PM5 random phase approximation method was the most promising for the prediction of λmax for anthraquinone dyes among the computational methods studied here. From the results of calculated gross population, pz, it was found that the value of pz using the time‐dependent density functional theory method was greater than the values calculated by semi‐empirical methods. The overestimation of pz could be attributed to the incorrect density functional theory calculation results. The results of PM5 random phase approximation‐calculated oscillator strength and torsion angle showed reasonable agreement with the observed results for sterically hindered anthraquinone dyes.

Rhubarb hydroxyanthraquinones act as antiobesity agents to inhibit adipogenesis and enhance lipolysis

Rhubarb as an herbal medicine has been shown to exhibit antiadipogenic activity. This study evaluated and compared the lipid-lowering activity of five rhubarb hydroxyanthraquinones (HAQs), including chrysophanol, aloe emodin, emodin, physcion, and rhein, aiming to identify candidate compounds for obesity treatment. Examination of the antiobesity effects of HAQs in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese rats showed that these anthraquinone compounds inhibited lipid accumulation in 3T3-L1 cells before and after differentiation. Emodin and rhein showed greater inhibition than the other compounds; dosage at 50 μM reduced intracellular triglyceride (TG) by about 30% in the differentiated adipocytes. Both compounds also revealed lipolytic effects to increase glycerol release from adipocytes. Adipokine overexpression induced by differentiation was downregulated by emodin and rhein through mitogen-activated protein kinase (MAPK) signaling. Despite their structural similarity, emodin and rhein exhibited different mechanisms on adipogenesis and lipid metabolism. Rhein restrained lipid deposition by controlling adipogenic transcriptional factors and lipolytic lipases during differentiation. The lipid-lowering effects of emodin did not use these pathways but reduced levels of lipogenic enzymes. HFD consumption in rats significantly increased body weight, visceral fat mass and adipocyte size, which were attenuated by intraperitoneal delivery of emodin or rhein. Rhein showed greater amelioration of obesity than emodin, decreasing plasma cholesterol by 29% and 14%, respectively. HAQs also suppressed cytokine upregulation in the liver and adipose tissues of obese rats. Rhein is a potential antiobesity agent through its ability to regulate obesity-associated adipogenesis, lipolysis and inflammation.

In vitro antidermatophytic activity of bioactive compounds from selected medicinal plants

Fungal infections are among the most difficult diseases to manage in humans. Eukaryotic fungal pathogens share many similarities with their host cells, which impairs the development of antifungal compounds. Therefore, it is desirable to harness the pharmaceutical potential of medicinal plants for antifungal drug discovery. In this study, the antifungal activity of sixteen plant extracts was investigated against selected dermatophytic fungi. Of the sixteen plants, the cladode (leaf) of Asparagus racemosus, and seed extract of Cassia occidentalis showed antifungal activity against Microsporum gypseum, Microsporum nanum, Trichophyton mentagrophytes and Trichophyton terrestre. The plant antifungal compounds were located by direct bioassay against Cladosporium herbarum. IR and NMR spectrometry analyses of these compounds identified the presence of saponin (in A. racemosus) and hydroxy anthraquinone (in C. occidentalis) in these antifungal compounds. The antidermatophytic activity of plant anthraquinone and saponins with reports of little or no hemolytic activity, makes these compounds ideal for alternative antifungal therapy and warrants further in-depth investigation in vivo.

Surface adsorption of hydroxyanthraquinones on CTAB-modified gold nanosurfaces

Gold nanosurfaces are widely applied to the surface-enhanced Raman spectroscopy (SERS) detection of the biological systems. The surface modification of gold nanoparticles (AuNPs) is often required when the analytes do not efficiently adsorb on the surface. In this paper, an aggregation of AuNPs with cetyltrimethylammonium bromide (CTAB) was introduced for the efficient surface adsorption and strong SERS enhancement for a number of hydroxyanthraquinones (HAQs). The SERS of HAQs including 1,2-dihydroxyanthraquinone (alizarin) were strongly enhanced with CTAB-modified AuNPs and deprotonation of alizarin was clearly observed upon the pH change. The CTAB-modified AuNPs are regarded as efficient SERS substrates for many biological molecules with weak surface adsorption.

Antitumour Anthracyclines: Progress and Perspectives.

Anthracyclines are ranked among the most effective chemotherapeutics against cancer. They are glycoside drugs comprising the amino sugar daunosamine linked to a hydroxy anthraquinone aglycone, and act by DNA intercalation, oxidative stress generation and topoisomerase II poisoning. Regardless of their therapeutic value, multidrug resistance and severe cardiotoxicity are important limitations of anthracycline treatment that have prompted the discovery of novel analogues. This review covers the most clinically relevant anthracyclines and their development over decades, since the first discovered natural prototypes to recent semisynthetic and synthetic derivatives. These include registered drugs, drug candidates undergoing clinical trials, and compounds under pre-clinical investigation. The impact of the structural modifications on antitumour activity, toxicity and resistance profile is addressed.

CHEMICAL CONSTITUENTS AND PHARMACOLOGICAL ACTIVITIES OF LANTANA CAMARA – A REVIEW

Objective: The review was designed to investigate the traditional uses, chemical constituents and pharmacological effects of Lantana camara.
 Methods: In the current review, databases including Web Science, Pub Med, Scopus and Science Direct, were searched to investigate the chemical constituents and pharmacological effects of Lantana camara.
 Results: The plant contained alkaloids, glycosides, steroids, saponins, flavanoids, coumarins, tannins, carbohydrates, hydroxy anthraquinones, anthraquinone glycosides, proteins, phytosteroids, fixed oils, fats, and triterpinoids. Previous pharmacological studies revealed that Lantana camara possessed antimicrobial, antiparasitic, anxiolytic, gastrointestinal, hypoglycemic, cardiovascular, antioxidant, anticancer, antiinflammatory, analgesic, wound healing, antiurolithiatic, hepatoprotective, reproductive, anti–hemorrhoidal, thrombin inhibition and many other effects.
 Conclusion: Lantana camara represents a promising medicinal plant with a wide range of pharmacological activities that could be utilized in several medical applications because of its effectiveness and safety.

Ingeniously regulating the antioxidant activities of hydroxyanthraquinone-based compounds via ESIPT reaction: Combining experiment and theory methods

The relationships between the excited state intramolecular proton transfer (ESIPT) behaviors and antioxidant activities of three hydroxyanthraquinone (HAQ) compounds containing 2,6-DHAQ, 1,5-DHAQ and 1,5-DAAQ were systematically explored via the experimental and theoretical methods. The measured femtosecond transient absorption indicates that 1,5-DAAQ exhibits the slower ESIPT reaction than 1,5-DHAQ due to its larger S1-state energy barrier in the scanned potential energy surfaces, which means that the transformation of 1,5-DAAQ from enol form to keto form is more difficult. Based on this, the antioxidant activities of the compounds in enol- and keto-form were studied. Concretely, the antioxidant activities of 1,5-DHAQ and 1,5-DAAQ in the keto form are stronger than that in the enol form, which is estimated from the calculated ionization potential (IP) values. In addition, compared with that at the S0 state, the involved three compounds in the enol and keto forms have the lower IPs at the S1 state, revealing that their antioxidant activities will be enhanced upon the photo-excitation. Derived from the difficulty of ESIPT reactions and antioxidant activities of the three compounds in the experiments and theory, it can be concluded that antioxidant activity of the compound can be regulated through the transformation of enol- and keto-form in the ESIPT reaction. This new discovery can help to design and synthesize more efficient ESIPT-based antioxidants in experiments.

Study on Preliminary Phytochemicals and GC-MS Analysis of Justicia adhatoda Leaves Extract

Several natural products have been implemented as an alternative health care treatment and in discovery of effective modern drugs. A major focus of natural product chemistry has been toward drug design and discovery. Justicia adhatoda is a well-known Indian medicinal plant valued for its pharmacopeia. This plant root, bark, leaf and flower are used to heal several diseases and poisonous bites. The present work was to evaluate the phytochemicals and GC-MS analysis of J. adhatoda leaves extracts. The extracts were subjected to qualitative phytochemical screening using standard procedures. The result showed that the phytochemicals present in the extract of J.adhatoda are alkaloids, flavonoids, glycosides, cardiac glycosides, coumarins, hydroxy anthraquinones, tannins, phlobatannins, proteins, xantho protein, steroids and phenols. The GC-MS analysis of acetone extract showed the presence of many secondary metabolites like phytol (0.8%), 9,12,15-octadecatrienoic acid, (Z,Z,Z) (1.6%), butane, 2,2-dimethyl (0.21%), pentane, 2,3,3-trimethyl (0.22%), hexathiane (0.08%), and benzenesulfonic acid (0.22%). The diversity of phytochemical present in the plant suggests that J. adhatoda could serve as a source of useful drugs.
 Keywords: Justicia adhatoda leaves, acetone extract, phytochemicals, GC-MS.

Fluorescence quenching and molecular docking study on the binding of four hydroxyanthraquinones to FTO

ABSTRACTIn this work, the binding of four hydroxyanthraquinones (HAQs) to fat mass and obesity-associated (FTO) protein has been studied using fluorescence, UV-vis absorption and circular dichroism spectroscopy as well as molecular docking analysis. Analysis of fluorescence data showed that the binding of HAQs to FTO occurred via a static quenching mechanism. Thermodynamic analysis and molecular docking results suggested that hydrophobic force played a major role in stabilising the HAQ-FTO complex. Circular dichroism spectra indicated that the secondary structure of FTO was changed by the addition of HAQs. Results also showed that emodin had the strongest quenching and binding ability among four HAQs.

Study of natural anthraquinone colorants by EPR and UV/vis spectroscopy

The spectroscopic study was performed on 9,10-anthraquinone derivatives (purpurin, alizarin, carminic acid, and 2-(hydroxymethyl)-9,10-anthraquinone) in dimethylsulfoxide in the presence of triethylamine to bring information on their protonation/deprotonation equilibria in aprotic solvent. An interesting deprotonation effect of 5,5-dimethyl-1-pyrroline N-oxide (a spin trapping agent used in the EPR experiments) was revealed. The quantum chemical calculations enabled the identification of the individual protonated/deprotonated tautomeric forms present in the experimental systems. The UV photoexcitation of hydroxyanthraquinones (HAQ) led to the generation of reactive radical species and singlet oxygen, detected by in situ EPR spectroscopy (spin trapping, nitroxide radical elimination, oxidation of sterically hindered amines). The changes in the electronic absorption spectra upon photoexcitation, linked with the ability of the studied HAQ to generate reactive oxygen species upon exposure, confirm a substantial effect of the substituent character and position on the overall photochemical behavior of the HAQ, significantly influenced by the actual experimental conditions (solvent, pH).

1,4-Dihydroxyanthraquinone-copper(II) nanoparticles immobilized on silica gel: a highly efficient, copper scavenger and recyclable heterogeneous nanocatalyst for a click approach to the three-component synthesis of 1,2,3-triazole derivatives in water

High yielding preparation of structurally different β-hydroxy 1,4-disubstituted 1,2,3-triazole from the regio-selective reaction of epoxides 2a–2c with wide range of terminal alkynes 1a–1j, and sodium azide in the presence of catalytic amount, complexed form of homogeneous catalyst [bis 1,4-mono ester hydroxy anthraquinone copper(II)] (5.0 mol%), [AQ2Cu(II)] 7 at 25 °C in water has been described. To benefit from the recovery and reuse of the catalyst, a novel heterogeneous nanoparticles of catalyst [bis 1,4-mono ester hydroxy anthraquinone copper(II) aminopropyl silica gel] (5.0 mol%), [AQ2Cu(II)-APSiO2] 13 bearing oxygen anthraquinone ligands with strong copper(II) affinity was easily prepared by using silica gel as a suitable support. The heterogeneous catalyst was fully characterized by XRD, SEM, AFM, ICP, TG methods for analysis of nitrogen adsorption, and FT-IR techniques. The remarkable features of this protocol are high yields, short reaction times, a cleaner reaction profile in an environmentally benign solvent (H2O), one-pot procedure and the method is applicable to large-scale operation without any problem. Furthermore, the catalyst could be recovered and easily removed by simple filtration of the reaction mixture and it was recycled ten times showing negligible copper leaching. In their uncomplexed form of homogeneous catalyst [AQ2Cu(II)] 7 and heterogeneous catalyst [AQ2Cu(II)-APSiO2] 13, the anthraquinone ligand 6 and [AQ-APSiO2] 12 are very efficient copper scavengers able to catalyze the 1,3-dipolar cycloaddition reaction of azides with alkynes (CuAAC) without pre-synthesis of catalysts.

Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-κB

Aloe emodin (AE), a natural anthraquinone, is reported to have antiproliferative activity in various cancer cell lines. In this study we analyzed molecular mechanisms involved in the antimigratory and antiangiogenic activity of this hydroxy anthraquinone in colon cancer cell, WiDr. Our results show that a relatively non toxic concentration of AE suppressed the phorbol-12-myristyl-13-acetate (PMA) induced migration and invasion of tumor cells. On analysis for the molecules involved in the migration/invasion, we found AE downregulated mRNA expression and promoter/gelatinolytic activity of Matrix Metalloproteinase (MMP)-2/9, as well as the RhoB expression at gene and protein level. It was also a strong inhibitor of Vascular Endothelial Growth Factor (VEGF) expression, promoter activity and endothelial cell migration/invasion and in vitro angiogenesis. AE suppressed the nuclear translocation and DNA binding of NF-κB, which is an important transcription factor for controlling MMP-2/9 and VEGF gene expression. Taken together these data indicate that AE target multiple molecules responsible for cellular invasion, migration and angiogenesis. Inhibitory effect on angiogenic and metastatic regulatory processes make AE a sensible candidate as a specific blocker of tumor associated events.

Use of Capillary Zone Electrophoresis and Micellar Electrokinetic Chromatography for Separations of Anthraquinone Derivatives

The behavior of seven hydroxy anthraquinone derivatives was studied by capillary zone electrophoresis and micellar electrokinetic chromatography. The effects of buffer pH (6.5–10.8) and sodium dodecyl sulfate concentration (10–20 mmol L−1) on the effective mobilities of the analytes and their separation were tested. A comparison of the two optimized separation systems showed that micellar electrokinetic chromatography was superior as it permits separation of all the seven analytes within 15 min, using 15 mmol L−1 sodium dodecyl sulfate in 10 mmol L−1 tetraborate buffer, pH 8.5, at a voltage of 20 kV. The calibration curves were linear in the concentration range from 5.0 · 10−7 to 5.0 · 10−4 mol L−1 for most of the analytes, at a detection wavelength of 254 nm. LOD and LOQ values of the analytes were in the ranges of 2.10 · 10−7–1.28 · 10−6 mol L−1and 6.99 · 10−7–4.25 · 10−6 mol L−1, respectively. The proposed separation conditions were applied to determination of 1,2-dihydroxy anthraquinone (alizarin) and 1,2,4-trihydroxy anthraquinone (purpurin) in Rubia tinctorum aglycone and of the recently described 1-acetyl-2,4,5,7-tetrahydroxy-9,10-anthraquinone and 1-acetyl-2,4,5,7,8-pentahydroxy-9,10-anthraquinone in the mycelium of fungi Geosmithia lavendula.

Microcalorimetric assay on the antimicrobial property of five hydroxyanthraquinone derivatives in rhubarb (Rheum palmatum L.) to Bifidobacterium adolescentis

It was found that the intestinal bacteria balance would be deteriorated by rhubarb especially in long term treatment. Bifidobacteria is one of the most common species of probiotics in human intestine. The suppression of this particular probiotic, such as Bifidobacterium adolescentis, one of the dominant anaerobes in the intestines of humans, might lead to imbalance of intestinal flora and is considered to be potentially riskful for human health. Hence, the inhibitory effects of the five main components of hydroxyanthraquinones (HAQs) contained in rhubarb on B. adolescentis growth were investigated by microcalorimetry to discover the suppression potential of rhubarb and the structure-function relationship of such HAQs. The value of the maximum power- output (P(max)) and slope (k) of the thermogenic growth curves of B. adolescentis were found of decrease in the presence of the five HAQs, while the peak time (T(p)) of the thermogenic curves were found to be delayed. The sequence of antimicrobial activity of the five HAQs is rhein>emodin>aloe-emodin>chrysophanol>physicion. The functional groups carboxyl, hydroxyl and hydroxylmethyl on phenyl ring in HAQs could improve the antimicrobial activity. The influence of substituent groups on anti- B. adolescentis activity might be related with the polarity and the sequence was carboxyl>hydroxyl>hydroxylmethyl>methyl and methoxyl.

Calorimetric investigation of the effect of hydroxyanthraquinones in Rheum officinale Baill on Staphylococcus aureus growth

The inhibitory effects of five hydroxyanthraquinones (HAQs) from root and rhizoma of Rheum officinale Baill, a traditional Chinese medicinal (TCM) herb, on Staphylococcus aureus growth were investigated by calorimetry. The power–time curves of S. aureus with and without HAQ were acquired and the extent and duration of inhibitory effects on the metabolism evaluated by growth rate constants ( k 1, k 2), half inhibitory ratio (IC 50), maximum heat output ( P max) and peak time ( t p). The value of k 1 and k 2 of S. aureus in the presence of the five HAQs decreased with the increasing concentrations of HAQs. Moreover, P max was reduced and the value of t p increased with increasing concentrations of the five drugs. The inhibitory activity varied for different drugs. IC 50 of the five HAQs was 4 μg ml −1 for emodin, 3.5 μg ml −1 for rhein, 10 μg ml −1 for aloe-emodin, 1000 μg ml −1 for chrysophanol, 1600 μg ml −1 for physcion. The sequence of antimicrobial activity of the five HAQs: rhein > emodin > aloe-emodin > chrysophanol > physicion.

An efficient regioselective synthesis of endocrocin and structural related natural anthraquinones starting from emodin

Endocrocin and related naturally occurring anthraquinone pigments like cinnalutein could be synthesized regioselectively via a Marschalk type reaction, starting from the natural hydroxy anthraquinone emodin. Furthermore, the new tri- O-methyl protected emodin-2-carbaldehyde may serve as a promising synthon for new bathochromically shifted, higher generation photodynamically active hypericin derivatives.

Impregnation of Hydroxy-Anthraquinone Compounds into Polypropylene Fabrics by scCO2 and the Sorption Ability for Metal Ions

Woven polypropylene fabrics were impregnated with hydroxy-anthraquinone (HAQ) derivatives compounds by supercritical carbon dioxide where the HAQ worked as a dyestuff. The HAQ-impregnated fabrics were tested to adsorb metal ions dissolved in water forming the “dye-metal chelate” under specific conditions of pH for one selected metal ion. The metal ions are believed to be trapped around the HAQ molecules by the hydroxyl groups, working as a mordant dyeing.