scholarly journals Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

2019 ◽  
Vol 15 ◽  
pp. 1933-1944 ◽  
Author(s):  
Silvie Rimpelová ◽  
Michal Jurášek ◽  
Lucie Peterková ◽  
Jiří Bejček ◽  
Vojtěch Spiwok ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Biological Effects ◽  
Sesquiterpene Lactones ◽  
Living Cells ◽  
Calcium Atpase ◽  
Dynamics Simulation ◽  
Plant Metabolites ◽  
Cytotoxic Effects ◽  
Secondary Plant Metabolites ◽  
Fluorescent Derivative

Sesquiterpene lactones are secondary plant metabolites with sundry biological effects. In plants, they are synthesized, among others, for pesticidal and antimicrobial effects. Two such compounds, archangelolide and trilobolide of the guaianolide type, are structurally similar to the well-known and clinically tested lactone thapsigargin. While trilobolide has already been studied by us and others, there are only scarce reports on the biological activity of archangelolide. Here we present the preparation of its fluorescent derivative based on a dansyl moiety using azide–alkyne Huisgen cycloaddition having obtained the two sesquiterpene lactones from the seeds of Laserpitium archangelica Wulfen using supercritical CO2 extraction. We show that dansyl-archangelolide localizes in the endoplasmic reticulum of living cells similarly to trilobolide; localization in mitochondria was also detected. This led us to a more detailed study of the anticancer potential of archangelolide. Interestingly, we found that neither archangelolide nor its dansyl conjugate did exhibit cytotoxic effects in contrast to the structurally closely related counterparts trilobolide and thapsigargin. We explain this observation by a molecular dynamics simulation, in which, in contrast to trilobolide, archangelolide did not bind into the sarco/endoplasmic reticular calcium ATPase cavity utilized by thapsigargin. Last, but not least, archangelolide exhibited anti-inflammatory activity, which makes it promising compound for medicinal purposes.

scholarly journals Archangelolide: Sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

2019 ◽  
Author(s):  
Silvie Rimpelová ◽  
Michal Jurášek ◽  
Lucie Peterková ◽  
Jiří Bejček ◽  
Vojtěch Spiwok ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cytotoxic Effect ◽  
Biological Effects ◽  
Sesquiterpene Lactones ◽  
Living Cells ◽  
Calcium Atpase ◽  
Dynamics Simulation ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites ◽  
Fluorescent Derivative

Sesquiterpene lactones are secondary plant metabolites with sundry biological effects. In plants, they are synthesized mainly for their pesticidal, antimicrobial and other effects. Two such compounds, archangelolide and trilobolide of the guaianolide type, are structurally similar to the well-known and clinically tested lactone thapsigargin. Here we present the development of a facile method for isolation of these two sesquiterpene lactones from the seeds of Laserpitium archangelica Wulfen using supercritical CO2 extraction. Furthermore, not much has been reported on biological activity of archangelolide. We prepared its fluorescent derivative based on a dansyl moiety using azide-alkyne Huisgen cycloaddition. We showed that dansyl-archangelolide localized in endoplasmic reticulum of living cells similarly to trilobolide; nevertheless, localization in mitochondria was also detected. This led us to study the anticancer potential of archangelolide. Interestingly, we found that neither archangelolide nor its dansyl conjugate did exhibit cytotoxic effect in contrast to its structurally closely related counterparts trilobolide and thapsigargin. We explain this observation by a molecular dynamics simulation, in which, in contrast to trilobolide, archangelolide did not bind into the sarco/endoplasmic reticular calcium ATPase cavity utilized by thapsigargin. Last, but not least, archangelolide exhibited anti-inflammatory activity, which makes it promising compound for medicinal purposes.

scholarly journals Polypharmacology of Some Medicinal Plant Metabolites Against SARS-CoV-2 and Host Targets: Molecular Dynamics Evaluation of NSP9 RNA Binding Protein

2020 ◽  
Author(s):  
Suritra Bandyopadhyay ◽  
Omobolanle Abimbola Abiodun ◽  
Blessing Chinweotito Ogboo ◽  
Adeola Tawakalitu Kola-Mustapha ◽  
Emmanuel Ifeanyi Attah ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Medicinal Plants ◽  
Active Sites ◽  
Rna Binding ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Receptor Interaction ◽  
Plant Metabolites ◽  
Structure Comparison

<p><b>Background: </b>Medicinal plants, as rich sources of bioactive compounds with antiviral properties, are now being explored for the development of drugs against SARS-CoV-2.</p><p><b>Aims: </b>Identification of promising compounds for the treatment of COVID-19 from natural products via molecular modelling against NSP9, including some other viral and host targets and evaluation of polypharmacological indications.</p><p><b>Main methods: </b>A manually curated library of 521 phytochemicals (from 19 medicinal plants) was virtually screened using Mcule server and binding interactions were studied using DS Visualiser. Docking thresholds were set based on the scores of standard controls and rigorous ADMET properties were used to finally get the potential inhibitors. Free binding energies of the docked complexes were calculated employing MM-GBSA method. MM-GBSA informed our choice for MD simulation studies performed against NSP9 to study the stability of the drug-receptor interaction. NSP9 structure comparison was also performed. </p><p><b>Key findings: </b>Extensive screening of the molecules identified 5 leads for NSP9, 23 for Furin, 18 for ORF3a, and 19 for interleukin-6. Ochnaflavone and Licoflavone B, obtained from Lonicera japonica (Japanese Honeysuckle) and Glycyrrhiza glabra (Licorice), respectively, were identified to have the highest potential multi-target inhibition properties for NSP9, furin, ORF3a, and IL-6. Additionally, molecular dynamics simulation supports the robust stability of Ochnaflavone and Licoflavone B against NSP9 at the active sites via hydrophobic interactions, H-bonding, and H-bonding facilitated by water.</p><b>Significance:</b> These compounds with the highest drug-like ranking against multiple viral and host targets have the potential to be drug candidates for the treatment of SARS-CoV-2 infection that may possibly act on multiple pathways simultaneously to inhibit viral entry and replication as well as disease progression.

scholarly journals Cocoa Flavanols: Natural Agents with Attenuating Effects on Metabolic Syndrome Risk Factors

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 751 ◽  
Author(s):  
Maria Jaramillo Flores
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Antioxidant Properties ◽  
Laboratory Animals ◽  
Protective Effects ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites

The interest in cacao flavanols is still growing, as bioactive compounds with potential benefits in the prevention of chronic diseases associated with inflammation, oxidative stress and metabolic disorders. Several analytical methodologies support that the flavanols in cacao-derived products can be absorbed, have bioactive properties, and thus can be responsible for their beneficial effects on human health. However, it must be considered that their biological actions and underlying molecular mechanisms will depend on the concentrations achieved in their target tissues. Based on the antioxidant properties of cacao flavanols, this review focuses on recent advances in research regarding their potential to improve metabolic syndrome risk factors. Additionally, it has included other secondary plant metabolites that have been investigated for their protective effects against metabolic syndrome. Studies using laboratory animals or human subjects represent strong available evidence for biological effects of cacao flavanols. Nevertheless, in vitro studies are also included to provide an overview of these phytochemical mechanisms of action. Further studies are needed to determine if the main cacao flavanols or their metabolites are responsible for the observed health benefits and which are their precise molecular mechanisms.

scholarly journals Blue Light Treatment but Not Green Light Treatment After Pre-exposure to UV-B Stabilizes Flavonoid Glycoside Changes and Corresponding Biological Effects in Three Different Brassicaceae Sprouts

2021 ◽  
Vol 11 ◽  
Author(s):  
Susanne Neugart ◽  
Petra Majer ◽  
Monika Schreiner ◽  
Éva Hideg
Keyword(s):  
Hydroxyl Radical ◽  
Blue Light ◽  
Biological Effects ◽  
Radical Scavenging ◽  
Green Light ◽  
Light Treatment ◽  
Flavonoid Glycosides ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites ◽  
Quercetin Glycosides

Ultraviolet-B (UV-B; 280–315 nm) radiation induces the biosynthesis of secondary plant metabolites such as flavonoids. Flavonoids could also be enhanced by blue (420–490 nm) or green (490–585 nm) light. Flavonoids act as antioxidants and shielding components in the plant’s response to UV-B exposure. They are shown to quench singlet oxygen and to be reactive to hydroxyl radical. The aim was to determine whether treatment with blue or green light can alter flavonoid profiles after pre-exposure to UV-B and whether they cause corresponding biological effects in Brassicaceae sprouts. Based on their different flavonoid profiles, three vegetables from the Brassicaceae were selected. Sprouts were treated with five subsequent doses (equals 5 days) of moderate UV-B (0.23 kJ m–2 day–1 UV-BBE), which was followed with two subsequent (equals 2 days) doses of either blue (99 μmol m–2 s–1) or green (119 μmol m–2 s–1) light. In sprouts of kale, kohlrabi, and rocket salad, flavonoid glycosides were identified by HPLC-DAD-ESI-MSn. Both Brassica oleracea species, kale and kohlrabi, showed mainly acylated quercetin and kaempferol glycosides. In contrast, in rocket salad, the main flavonol glycosides were quercetin glycosides. Blue light treatment after the UV-B treatment showed that quercetin and kaempferol glycosides were increased in the B. oleracea species kale and kohlrabi while—contrary to this—in rocket salad, there were only quercetin glycosides increased. Blue light treatment in general stabilized the enhanced concentrations of flavonoid glycosides while green treatment did not have this effect. Blue light treatment following the UV-B exposure resulted in a trend of increased singlet oxygen scavenging for kale and rocket. The hydroxyl radical scavenging capacity was independent from the light quality except for kale where an exposure with UV-B followed by a blue light treatment led to a higher hydroxyl radical scavenging capacity. These results underline the importance of different light qualities for the biosynthesis of reactive oxygen species that intercept secondary plant metabolites, but also show a pronounced species-dependent reaction, which is of special interest for growers.

scholarly journals Identification of Potential Phytochemical Inhibitors as Promising Therapeutics Against SARS-CoV-2 and Molecular Dynamics Simulation

2020 ◽  
Author(s):  
Anik Banik ◽  
Emran Sajib ◽  
Anamika Deb ◽  
Sheikh Rashel Ahmed ◽  
Md- Tariqul Islam ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Rna Binding ◽  
Viral Infections ◽  
Dynamics Simulation ◽  
Screening Methods ◽  
Plant Metabolites ◽  
Target Class ◽  
Drug Candidates ◽  
Preventive Medication

The high infectivity and mortality of novel coronavirus has caused a serious concern all over the world. Still, there is no specific drug or preventive medication to treat SARS-CoV-2 infection despite comprehensive analysis by the researchers. This study was designed to demonstrate the efficacy of some phyto-chemical compounds against SARS-CoV-2 by using both structure and ligand based virtual screening methods. A total of 33 plant metabolites were screened against SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding domain and HR2 domain using a molecular docking approach. Results showed that three metabolites, i.e., Limonin, Isoflavone, and Coumadin conferred maximum binding affinity with all key proteins of SARS-CoV-2. For each viral protein, the critical binding sites and drug surface hotspots have been unraveled. ADME analysis indicated that none of the compounds have adverse effects that could decrease their drug-like properties. Moreover, toxicity pattern analysis also unmasked the non-toxic nature of the top drug candidates. The RMSD values of top ligandmacromolecule complexes were less than 2 Å, while RMSF values showed regular atomic fluctuations in the molecular dynamics study. Notably, most of the target class by top drug candidates belonged to enzyme groups (e.g. oxidoreductases, protease, Kinase). Results of drug similarity prediction revealed two approved structural analogs of Coumadin named Warfarin (DB00682) and Phenprocoumon (DB00946) from DrugBank. In addition, Isoformononetin an experimental drug analog of isoflavone could also be an option for the treatment of viral infections. For limonin there was no analog found in drugbank. The study can pave the way for the creation of effective SARS-CoV-2 medications and preventive measures. We highly recommend further in vivo trials for the experimental validation of our findings

scholarly journals Identification of Potential Phytochemical Inhibitors as Promising Therapeutics Against SARS-CoV-2 and Molecular Dynamics Simulation

2020 ◽  
Author(s):  
Anik Banik ◽  
Emran Sajib ◽  
Anamika Deb ◽  
Sheikh Rashel Ahmed ◽  
Md- Tariqul Islam ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Rna Binding ◽  
Viral Infections ◽  
Dynamics Simulation ◽  
Screening Methods ◽  
Plant Metabolites ◽  
Target Class ◽  
Drug Candidates ◽  
Preventive Medication

The high infectivity and mortality of novel coronavirus has caused a serious concern all over the world. Still, there is no specific drug or preventive medication to treat SARS-CoV-2 infection despite comprehensive analysis by the researchers. This study was designed to demonstrate the efficacy of some phyto-chemical compounds against SARS-CoV-2 by using both structure and ligand based virtual screening methods. A total of 33 plant metabolites were screened against SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding domain and HR2 domain using a molecular docking approach. Results showed that three metabolites, i.e., Limonin, Isoflavone, and Coumadin conferred maximum binding affinity with all key proteins of SARS-CoV-2. For each viral protein, the critical binding sites and drug surface hotspots have been unraveled. ADME analysis indicated that none of the compounds have adverse effects that could decrease their drug-like properties. Moreover, toxicity pattern analysis also unmasked the non-toxic nature of the top drug candidates. The RMSD values of top ligandmacromolecule complexes were less than 2 Å, while RMSF values showed regular atomic fluctuations in the molecular dynamics study. Notably, most of the target class by top drug candidates belonged to enzyme groups (e.g. oxidoreductases, protease, Kinase). Results of drug similarity prediction revealed two approved structural analogs of Coumadin named Warfarin (DB00682) and Phenprocoumon (DB00946) from DrugBank. In addition, Isoformononetin an experimental drug analog of isoflavone could also be an option for the treatment of viral infections. For limonin there was no analog found in drugbank. The study can pave the way for the creation of effective SARS-CoV-2 medications and preventive measures. We highly recommend further in vivo trials for the experimental validation of our findings

scholarly journals Polypharmacology of Some Medicinal Plant Metabolites Against SARS-CoV-2 and Host Targets: Molecular Dynamics Evaluation of NSP9 RNA Binding Protein

2020 ◽  
Author(s):  
Suritra Bandyopadhyay ◽  
Omobolanle Abimbola Abiodun ◽  
Blessing Chinweotito Ogboo ◽  
Adeola Tawakalitu Kola-Mustapha ◽  
Emmanuel Ifeanyi Attah ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Medicinal Plants ◽  
Active Sites ◽  
Rna Binding ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Receptor Interaction ◽  
Plant Metabolites ◽  
Structure Comparison

<p><b>Background: </b>Medicinal plants, as rich sources of bioactive compounds with antiviral properties, are now being explored for the development of drugs against SARS-CoV-2.</p><p><b>Aims: </b>Identification of promising compounds for the treatment of COVID-19 from natural products via molecular modelling against NSP9, including some other viral and host targets and evaluation of polypharmacological indications.</p><p><b>Main methods: </b>A manually curated library of 521 phytochemicals (from 19 medicinal plants) was virtually screened using Mcule server and binding interactions were studied using DS Visualiser. Docking thresholds were set based on the scores of standard controls and rigorous ADMET properties were used to finally get the potential inhibitors. Free binding energies of the docked complexes were calculated employing MM-GBSA method. MM-GBSA informed our choice for MD simulation studies performed against NSP9 to study the stability of the drug-receptor interaction. NSP9 structure comparison was also performed. </p><p><b>Key findings: </b>Extensive screening of the molecules identified 5 leads for NSP9, 23 for Furin, 18 for ORF3a, and 19 for interleukin-6. Ochnaflavone and Licoflavone B, obtained from Lonicera japonica (Japanese Honeysuckle) and Glycyrrhiza glabra (Licorice), respectively, were identified to have the highest potential multi-target inhibition properties for NSP9, furin, ORF3a, and IL-6. Additionally, molecular dynamics simulation supports the robust stability of Ochnaflavone and Licoflavone B against NSP9 at the active sites via hydrophobic interactions, H-bonding, and H-bonding facilitated by water.</p><b>Significance:</b> These compounds with the highest drug-like ranking against multiple viral and host targets have the potential to be drug candidates for the treatment of SARS-CoV-2 infection that may possibly act on multiple pathways simultaneously to inhibit viral entry and replication as well as disease progression.

scholarly journals Are sesquiterpene lactones the elusive KARRIKIN-INSENSITIVE2 ligand?

Planta ◽  
2021 ◽  
Vol 253 (2) ◽  
Author(s):  
Mehran Rahimi ◽  
Harro Bouwmeester
Keyword(s):  
Auxin Transport ◽  
Sesquiterpene Lactones ◽  
Docking Studies ◽  
Hypocotyl Elongation ◽  
Microbial Activities ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites ◽  
High Affinity ◽  
Wide Range ◽  
Homology Models

Abstract Main conclusion The sunflower sesquiterpene lactones 8-epixanthatin and tomentosin can bind to the hydrophobic pocket of sunflower KAI2 with an affinity much higher than for the exogenous ligand KAR. Abstract Sesquiterpene lactones (STLs) are secondary plant metabolites with a wide range of biological, such as anti-microbial, activities. Intriguingly, the STLs have also been implicated in plant development: in several Asteraceae, STL levels correlate with the photo-inhibition of hypocotyl elongation. Although this effect was suggested to be due to auxin transport inhibition, there is no structural–functional evidence for this claim. Intriguingly, the light-induced inhibition of hypocotyl elongation in Arabidopsis has been ascribed to HYPOSENSITIVE TO LIGHT/KARRIKIN-INSENSITIVE2 (HTL/KAI2) signaling. KAI2 was discovered because of its affinity to the smoke-derived karrikin (KAR), though it is generally assumed that KAI2 has another, endogenous but so far elusive, ligand rather than the exogenous KARs. Here, we postulate that the effect of STLs on hypocotyl elongation is mediated through KAI2 signaling. To support this hypothesis, we have generated homology models of the sunflower KAI2s (HaKAI2s) and used them for molecular docking studies with STLs. Our results show that particularly two sunflower STLs, 8-epixanthatin and tomentosin, can bind to the hydrophobic pockets of HaKAI2s with high affinity. Our results are in line with a recent study, showing that these two STLs accumulate in the light-exposed hypocotyls of sunflower. This finding sheds light on the effect of STLs in hypocotyl elongation that has been reported for many decades but without conclusive insight in the elusive mechanism underlying this effect.

Sign in / Sign up

Export Citation Format

Share Document