Search Results (21)

Thirty-two fungal polyketide derivatives, including eleven new compounds, namely (3R,5′R)-5-hydroxytalaroflavone (1), talaroisochromenols A–C (3, 5, and 11), (8R,9R,10aR)-5-hydroxyaltenuene (13), (8R,9R,10aS)-5-hydroxyaltenuene (14), (8R,9S,10aR)-5-hydroxyaltenuene (15), nemanecins D and E (25 and 26), 2,5-dimethyl-8-iodochromone (27), and talarofurolactone A (29), together with one new naturally occurring but previously synthesized metabolite, 6-hydroxy-4-methoxycoumarin (28), were isolated and identified from the deep-sea cold-seep-derived fungus Talaromyces sp. CS-258. Among them, racemic ((±)-11) or epimeric (13–15, 25, and 26) mixtures were successfully separated by chiral or gradient elution HPLC. Meanwhile, compound 27 represents a rarely reported naturally occurring iodinated compound. Their planar structures as well as absolute configurations were determined by extensive analysis via NMR, MS, single-crystal X-ray diffraction, Mosher’s method, and ECD or NMR calculation (with DP4⁺ probability analysis). Possible biosynthetic routes of some isolated compounds, which are related to chromone or isochromone biosynthetic pathways, were put forward. The biological analysis results revealed that compounds 7, 9, 10, 18–22, 24, 30, and 31 showed broad-spectrum antibacterial activities against several human and aquatic pathogens with MIC ranges of 0.5–64 μg/mL. Full article

In this study, adsorbents based on molecularly imprinted polymers (MIPs) in two solid-phase extraction application forms, pipette tip and magnetic extraction, were used for the selective extraction of coumarins. The pipette-tip solid-phase extraction reduced solvent volumes; the magnetic MIP extraction was simple and effective for phase separation. Parameters affecting extraction, such as the amount of adsorbent, type of washing solvent, volume of the elution solvent, and extraction times for magnetic extraction, were optimized. The MIP-based adsorbents displayed high selectivity and extraction efficiency, resulting in recoveries ranging from 70.3 to 102.0% (RSD % less than 5.5%) for five coumarins under study, 6,7-dihydroxycoumarin-6-β-D-glucoside, coumarin, 7-methoxycoumarin, 6-methylcoumarin, and dicoumarol. The extracts were analyzed by high-performance liquid chromatography with diode array (DAD) and fluorescence (FLD) detectors, reaching limits of quantification of 0.5 and 0.9 µg·mL⁻¹ for coumarin and dicoumarol detected by DAD and 0.001–0.012 µg·mL⁻¹ for the other prohibited simple coumarins when used as a fragrance (detected by FLD). The proposed method was validated and its applicability was shown for the analysis of cosmetic samples like shower gel and perfume. Full article

The main phenolic compounds in the Hippophae rhamnoides fruit with potential therapeutic activities are quercetin-3-O-rhamnoside, quercetin-3-O-galactoside, myricetin, rutin, luteolin, kaempferol, vitexin, gallic acid, chlorogenic acid, caffeic acid, 7-methoxycoumarin, p-coumaric acid, and ferulic acid. Their general features recommend them for nutritional and therapeutic purposes, exploiting their neuroprotective and radioprotective effects. This study aims to investigate the potency of polyphenol-derived structures against dual tyrosine-regulated kinase, modulating neuroblastomas and glioblastomas in humans. Structural insights from the point of view of drug-like property assessment are also provided by Density Functional Theory (DFT) predictions on the lowest energy conformers, using the B3LYP/6-311G (d,p) method. Full article

In this paper, liquid–liquid chromatography was introduced for the first time for the separation of fingered citron (Citrus medica L. var. sarcodactylis Swingle). The fingered citron cultivated in Jinhua is of significant industrial and medicinal value, with several major coumarin compounds detected in its extract. Therefore, further separation for higher purity was of necessity. A preparative liquid–liquid chromatographic method was developed by combining two elution modes (isocratic and step-gradient) with selection according to different polarities of the target sample. Five coumarin derivatives—5,7-dimethoxycoumarin (52.6 mg, 99.6%), phellopterin (4.9 mg, 97.1%), 5-prenyloxy-7-methoxycoumarin (6.7 mg, 98.7%), 6-hydroxy-7-methoxycoumarin (7.1 mg, 82.2%), and byakangelicol (10.5 mg, 90.1%)—with similar structures and properties were isolated on a large scale from 100 mg of petroleum ether (PE) extract and 100 mg of ethyl acetate (EA) extract in Jinhua fingered citron. The productivity was much improved. The anti-growth activity of the isolated coumarins was evaluated against three cancer cell lines (HeLa, A549, and MCF7) with an MTT assay. The coumarins demonstrated potential anti-tumor activity on the HeLa cell line, with 5,7-dimethoxycoumarin in particular exhibiting the best anti-growth activity (IC₅₀ = 10.57 ± 0.24 μM) by inhibiting proliferation. It inhibited colony formation and reduced the size of the tumor sphere in a concentration-dependent manner. The main mechanism was confirmed as inducing apoptosis. This work was informative for further studies aimed at exploring new natural-product-based antitumor agents. Full article

Lavender is a valued plant due to its cosmetic, perfumery, culinary, and health benefits. A wide range of applications is related to the composition of bioactive compounds, the quantity and quality of which is determined by various internal and external factors, i.e., variety, morphological part of the plant, and climatic and soil conditions during vegetation. In the presented work, the characterization of antimicrobial properties as well as the qualitative and quantitative assessment of bioactive compounds in the form of polyphenols in ethanol extracts from leaves and flowers of Lavandula angustifolia Mill. intended for border hedges, cultivated in the region of southern Poland, were determined. The composition of the fraction of volatile substances and antioxidant properties were also assessed. The conducted research shows that extracts from leaves and flowers significantly affected the viability of bacterial cells and the development of mold fungi. A clear decrease in the viability of bacteria and C. albicans cells was shown in the concentration of 0.32% of extracts. Leaf extracts were characterized by a much higher content of polyphenols and antioxidant properties than flower extracts. The composition of volatiles measured by GC-MS was significantly different between the extracts. Linalyl acetate and ocimene isomers mix dominated in flower extracts, whereas coumarin, γ-cadinene, and 7-methoxycoumarin were identified as dominant in leaf extracts. Full article

Scientists have been interested in hybrid coumarin derivatives due to their wide clinical anticancer use. Herein, ethyl 8-methoxycoumarin-3-carboxylate (Compound 1) served as the starting material for the synthesis of a series of novel hybrid coumarin derivatives (Compounds 3–6). Their structure was determined using ¹³C NMR, ¹H NMR, elemental analysis, and mass spectrometry. The in vitro cytotoxic activities of coumarin derivatives (Compounds 3, 5, and 6) and brominated coumarin derivatives (Compounds 4, 8, and 9) against MCF-7 and MDA-MB-231 were evaluated. Several substances have been identified as promising candidates for future study, especially Compound 6 due to its potent activity against β-tubulin (TUB) polymerization, sulfatase, and aromatase enzymes. It also has a role in inducing cell-cycle arrest at the S phase in the MCF-7 cell line, as well as apoptosis. Full article

The objectives of this study were to investigate the melanogenetic potentials of the naturally occurring 7-hydroxy coumarin derivatives 7-hydroxy 5,6-dimethoxycoumarin (7H-5,6DM), 7-hydroxy 6,8-dimethoxycoumarin (7H-6,8DM), 7-hydroxy 6-methoxycoumarin (7H-6M), and 7-hydroxy 4-methylcoumarin (7H-4M) in the melanogenic cells model for murine B16F10 melanoma cells. The initial results indicated that melanin production and intracellular tyrosinase activity were significantly stimulated by 7H-4M but not by 7H-5,6DM, 7H-6,8DM, or 7H-6M. Therefore, our present study further investigated the melanogenic effects of 7H-4M in B16-F10 cells, as well as its mechanisms of action. In a concentration-dependent manner, 7H-4M increased intracellular tyrosinase activity, leading to the accumulation of melanin without affecting the viability of B16-F10 cells. Our study further investigated the effects of 7H-4M on melanogenesis, including its ability to promote tyrosinase activity, increase melanin content, and activate molecular signaling pathways. The results indicate that 7H-4M effectively stimulated tyrosinase activity and significantly increased the expression of melanin synthesis-associated proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and TRP2. Based on our findings, we can conclude that 7H-4M has the ability to activate the melanogenesis process through the upregulation of cAMP-dependent protein kinase (PKA) and the cAMP response element-binding protein (CREB). Additionally, our study showed that 7H-4M induced melanogenic effects by downregulating the extracellular signal-regulated kinase (ERK) and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthesis kinase-3β (GSK-3β) cascades, while upregulating the JNK and p38 signaling pathways. Finally, the potential of using 7H-4M in topical applications was tested through primary human skin irritation tests. During these tests, no adverse reactions were induced by 7H-4M. In summary, our results indicate that 7H-4M regulates melanogenesis through various signaling pathways such as GSK3β/β-catenin, AKT, PKA/CREB, and MAPK. These findings suggest that 7H-4M has the potential to prevent the development of pigmentation diseases. Full article

Metabolic activation is the primary cause of chemical toxicity including hepatotoxicity. Cytochrome P450 2E (CYP2E) is involved in this process for many hepatotoxicants, including acetaminophen (APAP), one of the most common analgesics and antipyretics. Although the zebrafish is now used as a model for toxicology and toxicity tests, the CYP2E homologue in zebrafish has not been identified yet. In this study, we prepared transgenic zebrafish embryos/larvae expressing rat CYP2E1 and enhanced green fluorescent protein (EGFP) using a β-actin promoter. Rat CYP2E1 activity was confirmed by the fluorescence of 7-hydroxycoumarin (7-HC), a metabolite of 7-methoxycoumarin that was specific for CYP2 in transgenic larvae with EGFP fluorescence (EGFP [+]) but not in transgenic larvae without EGFP fluorescence (EGFP [−]). APAP (2.5 mM) caused reduction in the size of the retina in EGFP [+] larvae but not in EGFP [−] larvae, while APAP similarly reduced pigmentation in both larvae. APAP at even 1 mM reduced the liver size in EGFP [+] larvae but not in EGFP [−] larvae. APAP-induced reduction of liver size was inhibited by N-acetylcysteine. These results suggest that rat CYP2E1 is involved in some APAP-induced toxicological endpoints in the retina and liver but not in melanogenesis of the developing zebrafish. Full article

To reveal the allelopathic effects of potato, seven compounds were isolated from the rhizosphere soil: 7-methoxycoumarin (1), palmitic acid (2), caffeic acid (3), chlorogenic acid (4), quercetin dehydrate (5), quercitrin (6), and rutin (7). Bioassays showed that compounds 1, 2, 4, and 6 had inhibitory effects on the growth of L. sativa and tissue culture seedlings of potato. The existence of the allelochemicals was confirmed by HPLC, and their contents were quantified with a total concentration of 9.02 μg/g in the rhizosphere soil of replanted potato. Approaches on the interactions of the allelochemicals and pathogens of potato including A. solani, B. cinerea, F. solani, F. oxysporum, C. coccodes, and V. dahlia revealed that compound 1 had inhibitory effects but compounds 2–4 promoted the colony growth of the pathogens. These findings demonstrated that the autotoxic allelopathy and enhancement of the pathogens caused by the accumulation of the allelochemicals in the continuously cropped soil should be one of the main reasons for the replant problems of potato. Full article

Root samples of sweet potato varieties originating from South Africa (‘Ndou’, ‘Bophelo’, ‘Monate’, and ‘Blesbok’), the USA (‘Beauregard’), and Peru (‘199062.1′) were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/QTOF/MS) and chemometrics to characterize and compare the locally developed varieties with well-known established overseas varieties. The highest total phenol content was detected in ‘Bophelo’, followed by ‘Beauregard’ and Peruvian variety ‘199062.1’. The Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) model classified the storage roots of six sweet potato varieties into two clusters. In the OPLS-DA scatter plot, one cluster, which included Peruvian variety ‘199062.1’, was separated from the others. L-tryptophan and 3-caffeoylquinic acid (CQA) showed variable importance in projection (VIP) scores greater than 1.5. Based on the OPLS-DA-S-plot, L-tryptophan separated the other varieties from Peruvian variety ‘199062.1’. Peruvian variety ‘199062.1’ contained higher concentrations of CQA (1,3-diCQA, 1,4-diCQA, 3,5-diCQA, 4,5-diCQA, 3-CQA, and 5-CQA) and 5-hydroxy-6-methoxycoumarin 7-glucoside than other varieties. Among all sweet potato varieties analyzed, Peruvian variety ‘199062.1′ showed the highest ferric reducing antioxidant power (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical scavenging activity, and [2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonate)] scavenging activity. Among the local sweet potato varieties, ‘Bophelo’ has the greatest potential for commercialization as it is the richest source of CQA. Full article

Peroxisome proliferator-activated receptor γ (PPARγ) is a molecular target of metabolic syndrome and inflammatory disease. PPARγ is an important nuclear receptor and numerous PPARγ ligands were developed to date; thus, efficient assay methods are important. Here, we investigated the incorporation of 7-diethylamino coumarin into the PPARγ agonist rosiglitazone and used the compound in a binding assay for PPARγ. PPARγ-ligand-incorporated 7-methoxycoumarin, 1, showed weak fluorescence intensity in a previous report. We synthesized PPARγ-ligand-incorporating coumarin, 2, in this report, and it enhanced the fluorescence intensity. The PPARγ ligand 2 maintained the rosiglitazone activity. The obtained partial agonist 6 appeared to act through a novel mechanism. The fluorescence intensity of 2 and 6 increased by binding to the ligand binding domain (LBD) of PPARγ and the affinity of reported PPARγ ligands were evaluated using the probe. Full article

The plant kingdom has always been a treasure trove for valuable bioactive compounds, and Citrus fruits stand out among the others. Bergamottin (BRG) and 5-geranyloxy-7-methoxycoumarin (5-G-7-MOC) are two coumarins found in different Citrus species with well-acknowledged pharmacological properties. Previously, they have been claimed to be relevant in the anti-proliferative effects exerted by bergamot essential oil (BEO) in the SH-SY5Y human neuroblastoma cells. This study was designed to verify this assumption and to assess the mechanisms underlying the anti-proliferative effect of both compounds. Our results demonstrate that BRG and 5-G-7-MOC are able to reduce the proliferation of SH-SY5Y cells, inducing apoptosis and increasing cell population in sub-G0/G1 phase. Moreover, we demonstrated the pro-oxidant activity of the two coumarins that increased reactive oxygen species and impaired mitochondrial membrane potential. From a molecular point of view, BRG and 5-G-7-MOC were able to modulate apoptosis related factors at both protein and gene levels. Lastly, we evaluated the synergistic effect of their combination, finding that the highest synergy was observed at a concentration ratio similar to that occurring in the BEO, supporting our initial hypothesis. Taken together, our results deepen the knowledge regarding the effect of BRG and 5-G-7-MOC in SH-SY5Y cells, emphasizing the relevance of their cooperation in achieving this effect. Full article

Coumarins are natural products with promising pharmacological activities owing to their anti-inflammatory, antioxidant, antiviral, anti-diabetic, and antimicrobial effects. Coumarins are present in many plants and microorganisms and have been widely used as complementary and alternative medicines. To date, the pharmacological efficacy of 4-hydroxy-7-methoxycoumarin (4H-7MTC) has not been reported yet. Therefore, in this study, we investigated the anti-inflammatory effects of 4H-7MTC in LPS-stimulated RAW264.7 cells as well as its mechanisms of action. Cells were treated with various concentrations of 4H-7MTC (0.3, 0.6, 0.9, and 1.2 mM) and 40 μM L-N⁶-(1-iminoethyl)-L-lysine (L-NIL) were used as controls. LPS-stimulated RAW264.7 cells showed that 4H-7MTC significantly reduced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production without cytotoxic effects. In addition, 4H-7MTC strongly decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Furthermore, 4H-7MTC reduced the production of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. We also found that 4H-7MTC strongly exerted its anti-inflammatory actions by downregulating nuclear factor kappa B (NF-κB) activation by suppressing inhibitor of nuclear factor kappa B alpha (IκBα) degradation in macrophages. Moreover, 4H-7MTC decreased phosphorylation of extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK), but not that of p38 MAPK. These results suggest that 4H-7MTC may be a good candidate for the treatment or prevention of inflammatory diseases such as dermatitis, psoriasis, and arthritis. Ultimately, this is the first report describing the effective anti-inflammatory activity of 4H-7MTC. Full article

Extensive phytochemical analysis of different root fractions of Jatropha pelargoniifolia Courb. (Euphorbiaceae) has resulted in the isolation and identification of 22 secondary metabolites. 6-hydroxy-8-methoxycoumarin-7-O-β-d-glycopyranoside (15) and 2-hydroxymethyl N-methyltryptamine (18) were isolated and identified as new compounds along with the known diterpenoid (1, 3, 4, and 7), triterpenoid (2 and 6), flavonoid (5, 11, 13, 14, and 16), coumarinolignan (8–10), coumarin (15), pyrimidine (12), indole (17, 18), and tyramine-derived molecules (19–22). The anti-inflammatory, analgesic, and antipyretic activities were evaluated for fifteen of the adequately available isolated compounds (1–6, 8–11, 13, 14, 16, 21, and 22). Seven (4, 6, 10, 5, 13, 16, and 22) of the tested compounds showed a significant analgesic effect ranging from 40% to 80% at 10 mg/kg in two in vivo models. Compound 1 could also prove its analgesic property (67.21%) when it was evaluated on a third in vivo model at the same dose. The in vitro anti-inflammatory activity was also recorded where all compounds showed the ability to scavenge nitric oxide (NO) radical in a dose-dependent manner. However, eight compounds (1, 4, 5, 6, 10, 13, 16, and 22) out of the fifteen tested compounds exhibited considerable in vivo anti-inflammatory activity which reached 64.91% for compound 10 at a dose of 10 mg/kg. Moreover, the tested compounds exhibited an antipyretic effect in a yeast-induced hyperthermia in mice. The activity was found to be highly pronounced with compounds 1, 5, 6, 10, 13, and 16 which decreased the rectal temperature to about 37 °C after 2 h of the induced hyperthermia (~39 °C) at a dose of 10 mg/kg. This study could provide scientific evidence for the traditional use of J. pelargoniifolia as an anti-inflammatory, analgesic, and antipyretic. Full article

The tree popularly known in Brazil as mulateiro or pau-mulato (Calycophyllum spruceanum (Benth.) K. Schum.) is deeply embedded in the herbal medicine of the Amazon region. Different preparations of the bark are claimed to have anti-aging, antioxidant, antimicrobial, emollient, wound healing, hemostatic, contraceptive, stimulant, and anti-diabetic properties. The current study aims to provide the first step towards a science-based evidence of the beneficial effects of C. spruceanum in the promotion of longevity and in the modulation of age-related markers. For this investigation, we used the model system Caenorhabditis elegans to evaluate in vivo antioxidant and anti-aging activity of a water extract from C. spruceanum. To chemically characterize the extract, HPLC MS (High Performance Liquid Chromatography Mass Spectrometry)/MS analyses were performed. Five secondary metabolites were identified in the extract, namely gardenoside, 5-hydroxymorin, cyanidin, taxifolin, and 5-hydroxy-6-methoxycoumarin-7-glucoside. C. spruceanum extract was able to enhance stress resistance and to extend lifespan along with attenuation of aging-associated markers in C. elegans. The demonstrated bioactivities apparently depend on the DAF-16/FOXO pathway. The data might support the popular claims of mulateiro as the “tree of youth”, however more studies are needed to clarify its putative benefits to human health. Full article