scholarly journals A Collection of Bioactive Nitrogen-Containing Molecules from the Marine Sponge Acanthostrongylophora ingens

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 472 ◽  
Author(s):  
Germana Esposito ◽  
Linh H. Mai ◽  
Arlette Longeon ◽  
Alfonso Mangoni ◽  
Emilie Durieu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Alzheimer’S Disease ◽  
Antimicrobial Activity ◽  
Nmr Spectroscopy ◽  
Marine Sponge ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Two Dimensional ◽  
Esi Ms ◽  
First Time

Thirteen nitrogen-containing molecules (1a/1b and 2–12) were isolated from the Indonesian sponge Acanthostrongylophora ingens, highlighting the richness of this organism as a source of alkaloids. Their structures were elucidated using one- and two-dimensional NMR spectroscopy and HR-ESI-MS, while the stereochemistry of the diketopiperazines was established using Marfey’s method. All compounds were screened in our standard bioactivity assays, including antibacterial, antikinases, and amyloid β-42 assays. The most interesting bioactivity result was obtained with the known acanthocyclamine A (3), which revealed for the first time a specific Escherichia coli antimicrobial activity and an inhibitory effect on amyloid β-42 production induced by aftin-5 and no cytotoxicity at the dose of 26 µM. These results highlight the potentiality of a bipiperidine scaffold as a promising skeleton for preventing or reducing the production of amyloid β-42, a key player in the initiation of Alzheimer’s disease.

scholarly journals Perphenazine-macrocycle conjugates divert Aβ42 towards non-toxic aggregates by monomer sequestration

2020 ◽  
Author(s):  
Sarah R Ball ◽  
Julius S P Adamson ◽  
Michael A Sullivan ◽  
Manuela R Zimmermann ◽  
Victor Lo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nmr Spectroscopy ◽  
Kinetic Analysis ◽  
Amyloid Β ◽  
Dimensional Structure ◽  
Amyloid Β Peptide ◽  
Monomeric Form ◽  
Starting Point ◽  
The Impact

AbstractThe amyloid-β peptide, the main protein component of amyloid plaques in Alzheimer’s disease, plays a key role in the neurotoxicity associated with the condition through the formation of small toxic oligomer species which mediate the disruption of calcium and glutamate homeostasis. The lack of therapeutic benefit associated with removal of mature amyloid-β fibrils has focused attention on the toxic oligomeric species formed during the process of fibril assembly. Here, we present the design and synthesis of a family of perphenazine-macrocyle conjugates. We find that two-armed perphenazine-cyclam conjugates divert the monomeric form of the amyloid-β peptide away from the amyloidogenic pathway into amorphous aggregates that are not toxic to differentiated SH-SY5Y cells in vitro. This strategy prevents the formation of damaging amyloid oligomers. Kinetic analysis of the effects of these compounds on the assembly pathway, together with NMR spectroscopy, identifies rapid monomer sequestration as the underlying neuroprotective mechanism. The ability to specifically target the monomeric form of amyloid-β allows for further understanding of the impact of the multiple species formed between peptide biogenesis and plaque deposition. The modular, three-dimensional structure of these compounds provides a starting point for the design of more potent modulators of this amyloid-forming peptide, and can be adapted to probe the protein self-assembly pathways associated with other proteinopathies.Significance statementThe aggregation pathway of the amyloid-β (Aβ) peptide in Alzheimer’s disease is complex and involves multiple different species. An inability to isolate and study the impact of distinct Aβ species has undermined efforts to develop effective therapies. To address this issue, we have developed a series of molecules that specifically sequester the monomeric form of the highly aggregation-prone Aβ42 peptide. Interaction with these molecules diverts Aβ42 from the amyloidogenic pathway and prevents formation of toxic oligomeric species. We use kinetic analysis and NMR spectroscopy to identify rapid monomer sequestration as the underlying neuroprotective mechanism. Future rational development of these molecules and characterisation of their interactions with Aβ will delineate the impact of different Aβ oligomers on neurobiology and pathology.

scholarly journals The inhibition of cellular toxicity of amyloid-β by dissociated transthyretin

2020 ◽  
Vol 295 (41) ◽  
pp. 14015-14024 ◽  
Author(s):  
Qin Cao ◽  
Daniel H. Anderson ◽  
Wilson Y. Liang ◽  
Joshua Chou ◽  
Lorena Saelices
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Effect ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Aβ Oligomers ◽  
Cellular Toxicity ◽  
Computational Docking

The protective effect of transthyretin (TTR) on cellular toxicity of β-amyloid (Aβ) has been previously reported. TTR is a tetrameric carrier of thyroxine in blood and cerebrospinal fluid, the pathogenic aggregation of which causes systemic amyloidosis. However, studies have documented a protective effect of TTR against cellular toxicity of pathogenic Aβ, a protein associated with Alzheimer's disease. TTR binds Aβ, alters its aggregation, and inhibits its toxicity both in vitro and in vivo. In this study, we investigate whether the amyloidogenic ability of TTR and its antiamyloid inhibitory effect are associated. Using protein aggregation and cytotoxicity assays, we found that the dissociation of the TTR tetramer, required for its amyloid pathogenesis, is also necessary to prevent cellular toxicity from Aβ oligomers. These findings suggest that the Aβ-binding site of TTR may be hidden in its tetrameric form. Aided by computational docking and peptide screening, we identified a TTR segment that is capable of altering Aβ aggregation and toxicity, mimicking TTR cellular protection. EM, immune detection analysis, and assessment of aggregation and cytotoxicity revealed that the TTR segment inhibits Aβ oligomer formation and also promotes the formation of nontoxic, nonamyloid amorphous aggregates, which are more sensitive to protease digestion. Finally, this segment also inhibits seeding of Aβ catalyzed by Aβ fibrils extracted from the brain of an Alzheimer's patient. Together, these findings suggest that mimicking the inhibitory effect of TTR with peptide-based therapeutics represents an additional avenue to explore for the treatment of Alzheimer's disease.

scholarly journals ANTIMICROBIAL ACTIVITY OF SELECTED INDIAN FOLK MEDICINAL PLANTS: MYRISTICA FATUA, ALSTONIA BOONEI, HELICTERES ISORA, VITEX ALTISSIMA AND ATALANTIA RACEMOSA

2017 ◽  
Vol 10 (2) ◽  
pp. 277
Author(s):  
Kokkaiah Irulandi ◽  
Sethupandian Geetha ◽  
Palanichamy Mehalingam
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Bacillus Subtilis ◽  
Ethyl Acetate ◽  
Inhibitory Effect ◽  
Diffusion Method ◽  
Alternative Source ◽  
Helicteres Isora ◽  
Acetone Extracts

Objective: To determine antimicrobial activity of methanol, ethyl acetate and acetone extracts of Myristica fatua, Alstonia boonei, Helicteres isora, Vitex altissima and Atalantia racemosa  against different species of pathogens, Streptococcus feacalis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacillus subtilis, Staphyllococcus aureus, and Candida albicans.Methods: Antimicrobial activity of plant extracts was measured by agar well diffusion method.Results: Acetone extracts of Alstonia boonei showed the highest inhibitory effect against Escherichia coli (21.00 ± 1.00 mm) and Streptococcus faecalis (19.00 ± 1.00 mm). All the extracts of Heliteres isora leaves showed different zone of inhibition observed in all the tested pathogens ranges between (8.13 ± 1.53 – 15.25 ± 1.23 mm). Ethyl acetate extract of Vitex altissima showed highest activity against Bacillus sublilis (19.67 ± 1.53 mm). Methanol and acetone leaves extracts of Atalantia racemosa have good fungal activity against the Candida albicans (19.33 ± 1.26 mm - 16.00 ± 1.00 mm). Methanol extract of Myristica fatua showed high antimicrobial activity against Pseudomonas aeruginosa (15.10 ± 0.17 mm) and Bacillus subtilis (14.23 ± 0.21 mm).Conclusion: The results from the study suggest that the leaves Myristica fatua, Alstonia boonei, Helicteres isora, Vitex altissima and Atalantia racemosa showed good antimicrobial activity against the different pathogens. They are used as the alternative source for the control and treatment of microbial infections.Keywords: Antimicrobial activity, Leaves extracts,  Well diffusion method, Pathogenic strains.

scholarly journals Ircinal E, a New Manzamine Derivative from the Indonesian Marine Sponge Acanthostrongylophora ingens

2015 ◽  
Vol 10 (11) ◽  
pp. 1934578X1501001 ◽  
Author(s):  
Mousa AlTarabeen ◽  
Georgios Daletos ◽  
Weaam Ebrahim ◽  
Werner E. G. Müller ◽  
Rudolf Hartmann ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Nmr Spectroscopy ◽  
High Resolution ◽  
Cell Line ◽  
Marine Sponge ◽  
High Resolution Mass Spectrometry ◽  
Two Dimensional ◽  
Meoh Extract ◽  
L5178y Cell ◽  
Resolution Mass

Chemical investigation of the MeOH extract of the sponge Acanthostrongylophora ingens afforded the new manzamine derivative ircinal E (1), in addition to six known metabolites (2–7). The structure of the new compound was unequivocally elucidated using one- and two-dimensional NMR spectroscopy, as well as high-resolution mass spectrometry. Compounds 1–6 exhibited strong to moderate cytotoxicity against the murine lymphoma L5178Y cell line with IC50 values ranging from 2.8 to 21.7 μM.

scholarly journals Comparative Study of Naphthoquinone Contents of Selected Greek Endemic Boraginaceae Plants - Antimicrobial Activities

2017 ◽  
Vol 12 (2) ◽  
pp. 1934578X1701200
Author(s):  
Teisa Tufa ◽  
Harilaos Damianakos ◽  
Konstantia Graikou ◽  
Ioanna Chinou
Keyword(s):  
Antimicrobial Activity ◽  
Nmr Spectroscopy ◽  
Comparative Study ◽  
Pathogenic Fungi ◽  
2D Nmr ◽  
Antimicrobial Activities ◽  
2D Nmr Spectroscopy ◽  
Chromatographic Separations ◽  
Esi Ms ◽  
Related Compounds

The cyclohexane (Ch) extracts of the roots of five Greek endemic Boraginaceae plants, Onosma kaheirei Teppner, O. graeca Boiss., O. erecta Sibth. & Sm., Alkanna sfikasiana Kit Tan, Vold and Strid and Cynoglossum columnae Ten, were investigated for the presence of alkannin/shikonin-related compounds. All species, s except C. columnae and O. erecta, were found to contain this type of compounds. Seven compounds were obtained after several chromatographic separations from the Ch extracts of the investigated plants: deoxyalkannin (1), 2″-( S)- α-methylbutyrylalkannin (2), isobutyrylalkannin (3), propionylalkannin (4), acetylalkannin (5), β-hydroxyisovalerylalkannin (6), and β,β-dimethylacrylalkannin (7). All structures were identified by 1D 1H-/13C- and 2D NMR spectroscopy, assisted also by ESI-MS. The extracts and the isolated compounds exhibiting an interesting antimicrobial profile when evaluated for their antimicrobial activity against six Gram-positive and -negative bacteria and three human pathogenic fungi.

Antimicrobial activity of selected lactic acid cocci and production of organic acids

2012 ◽  
Vol 5 (1) ◽  
pp. 80-85 ◽  
Author(s):  
Zuzana Hladíková ◽  
Jana Smetanková ◽  
Gabriel Greif ◽  
Mária Greifová
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Lactic Acid ◽  
Organic Acids ◽  
Rhizopus Oryzae ◽  
Streptococcus Thermophilus ◽  
Inhibitory Effect ◽  
Penicillium Funiculosum ◽  
Phenyllactic Acid ◽  
Indicator Microorganisms

Antimicrobial activity of selected lactic acid cocci and production of organic acidsAntimicrobial activity and production of organic acids by selected lactic acid bacteria were monitored in this study. The largest antimicrobial activity against indicator microorganisms showed Pediococcus sp. G5, whereasStreptococcus thermophilushad no inhibitory effect. The inhibitory effect ofPediococcussp. G5 was strongest againstBacillus subtilis(17.78 %). Lactococci inhibited the growth ofEscherichia coli, Pseudomonas aeruginosaandStaphylococcus aureus(% of inhibition ≤ 5.25). The growth ofAsperglillus flavus, Penicillium funiculosumandRhizopus oryzaewas not inhibited by all of tested cocci. Cocci produced varying quantities of organic acids (lactic acid, acetic acid, succinic acid, etc.). Lactic acid was in large amounts and phenyllactic acid was produced only byPediococcussp. G5 (49.65 mg/L).

scholarly journals Chemical Constituents from the Fruits ofForsythia suspensaand Their Antimicrobial Activity

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ping-Chung Kuo ◽  
Guo-Feng Chen ◽  
Mei-Lin Yang ◽  
Ya-Hua Lin ◽  
Chi-Chung Peng
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Column Chromatography ◽  
Chemical Constituents ◽  
Phenylethanoid Glycosides ◽  
Natural Sources ◽  
Methanol Extracts ◽  
Lead Compounds ◽  
Forsythia Suspensa ◽  
First Time

Lignans and phenylethanoid glycosides purified fromForsythia suspensawere reported to display various bioactivities in the previous literature, including the antimicrobial activity. Therefore, the present research is aimed to purify and identify the chemical constituents of the methanol extracts of fruits ofF. suspensa. The methanol extracts of fruits ofF. suspensawere fractionated and further purified with the assistance of column chromatography to afford totally thirty-four compounds. Among these isolates, 3β-acetoxy-20α-hydroxyursan-28-oic acid (1) was reported from the natural sources for the first time. Some of the purified principles were subjected to the antimicrobial activity examinations againstEscherichia colito explore new natural lead compounds.

Impairment of the activity of the plasma membrane Ca2+-ATPase in Alzheimer's disease

2011 ◽  
Vol 39 (3) ◽  
pp. 819-822 ◽  
Author(s):  
Ana M. Mata ◽  
María Berrocal ◽  
M. Rosario Sepúlveda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid

AD (Alzheimer's disease) is an age-associated neurodegenerative disorder where the accumulation of neurotoxic Aβ (amyloid β-peptide) in senile plaques is a typical feature. Recent studies point out a relationship between Aβ neurotoxicity and Ca2+ dyshomoeostasis, but the molecular mechanisms involved are still under discussion. The PMCAs (plasma membrane Ca2+-ATPases) are a multi-isoform family of proteins highly expressed in brain that is implicated in the maintenance of low intraneural Ca2+ concentration. Therefore the malfunction of this pump may also be responsible for Ca2+ homoeostasis failure in AD. We have found that the Ca2+-dependence of PMCA activity is affected in human brains diagnosed with AD, being related to the enrichment of Aβ. The peptide produces an inhibitory effect on the activity of PMCA which is isoform-specific, with the greatest inhibition of PMCA4. Besides, cholesterol blocked the inhibitory effect of Aβ, which is consistent with the lack of any Aβ effect on PMCA4 found in cholesterol-enriched lipid rafts isolated from pig brain. These observations suggest that PMCAs are a functional component of the machinery that leads to Ca2+ dysregulation in AD and propose cholesterol enrichment in rafts as a protector of the Aβ-mediated inhibition on PMCA.

scholarly journals Observation of Multinuclear Extra-framework Aluminum Species in Dealuminated Zeolite Catalysts

2020 ◽  
Author(s):  
Anmin Zheng ◽  
Xianfeng Yi ◽  
Yao Xiao ◽  
Zhiqiang Liu ◽  
Guangchao Li ◽  
...  
Keyword(s):  
Solid State ◽  
Nmr Spectroscopy ◽  
Zeolite Catalysts ◽  
Two Dimensional ◽  
Thermal Stabilities ◽  
Acidic Sites ◽  
Transformation Mechanisms ◽  
First Time ◽  
Intense Debate ◽  
Catalytic Performances

Abstract Although the Lewis acidic extra-framework aluminum (EFAL) species usually play decisive roles in improving the thermal stabilities, acidity and catalytic performances of industrialized zeolitic catalysts, the structure of these important EFAL clusters has long been a subject of intense debate, and their characterization remains a challenging task. Particularly, the more stable and even more catalytic active multinuclear EFAL clusters have never been experimentally observed owing to the nearly indistinguishable physicochemical properties of mononuclear and multinuclear EFAL species detected by conventional techniques. Herein, by invoking advanced two-dimensional (2D) solid-state 31P NMR spectroscopy in conjunction with a novel probe molecule, namely 1,2-bis(dimethylphosphine) ethane (DMPE), we demonstrated for the first time that the presence of multinuclear EFAL species in dealuminated zeolites. Furthermore, based on the comprehensive spatial interactions information from 2D 31P-31P homonuclear correlation NMR experiments, the evolution and transformation mechanisms of various acidic sites during the dealumination treatment of zeolites have also been clarified.

scholarly journals Bio-Guided Fractionation of Prenylated Benzaldehyde Derivatives as Potent Antimicrobial and Antibiofilm from Ammi majus L. Fruits-Associated Aspergillus amstelodami

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4118 ◽  
Author(s):  
Noha Fathallah ◽  
Marwa M. Raafat ◽  
Marwa Y. Issa ◽  
Marwa M. Abdel-Aziz ◽  
Mokhtar Bishr ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Streptococcus Mutans ◽  
Endophytic Fungus ◽  
Inhibitory Concentration ◽  
Antibiofilm Activity ◽  
Moderate Activity ◽  
Ammi Majus ◽  
First Time

Ammi majus L.; Family Apiaceae; is a plant indigenous to Egypt. Its fruits contain bioactive compounds such as furanocoumarins and flavonoids of important biological activities. An endophytic fungus was isolated from the fruits and identified as Aspergillus amstelodami (MK215708) by morphology, microscopical characterization, and molecular identification. To our knowledge this is the first time an endophytic fungus has been isolated from the fruits. The antimicrobial activity of the Ammi majus ethanol fruits extract (AME) and fungal ethyl acetate extract (FEA) were investigated, where the FEA showed higher antimicrobial activity, against all the tested standard strains. Phytochemical investigation of the FEA extract yielded five prenylated benzaldehyde derivative compounds isolated for the first time from this species: Dihydroauroglaucin (1), tetrahydroauroglaucin (2), 2-(3,6-dihydroxyhepta-1,4-dien-1-yl)-3,6-dihydroxy-5-(dimethylallyl)benzaldehyde (3), isotetrahydroauroglaucin )4), and flavoglaucin (5). Structure elucidation was carried out using (1H- and 13C-NMR). Fractions and the major isolated compound 1 were evaluated for their antimicrobial and antibiofilm activity. Compound 1 showed high antimicrobial activity against Escherichia coli with minimum inhibitory concentration (MIC) = 1.95 µg/mL, Streptococcus mutans (MIC = 1.95 µg/mL), and Staphylococcus aureus (MIC = 3.9 µg/mL). It exhibited high antibiofilm activity with minimum biofilm inhibitory concentration (MBIC) = 7.81 µg/mL against Staphylococcus aureus and Escherichia coli biofilms and MBIC = 15.63 µg/mL against Streptococcus mutans and Candida albicans and moderate activity (MBIC = 31.25 µg/mL) against Pseudomonas aeruginosa biofilm. This reveals that dihydroauroglaucin, a prenylated benzaldehyde derivative, has a broad spectrum antimicrobial activity. In conclusion, it was observed that the MICs of the FEA are much lower than that of the AME against all susceptible strains, confirming that the antimicrobial activity of Ammi majus may be due to the ability of its endophytic fungi to produce effective secondary metabolites.

Sign in / Sign up

Export Citation Format

Share Document