scholarly journals Artemisinin-independent inhibitory activity of Artemisia sp. infusions against different Plasmodium stages including relapse-causing hypnozoites

2021 ◽  
Author(s):  
Kutub Ashraf ◽  
Shahin Tajeri ◽  
Christophe-Sébastien Arnold ◽  
Nadia Amanzougaghene ◽  
Jean-François Franetich ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Inhibitory Activity ◽  
Parasite Species ◽  
Artemisia Annua ◽  
Plasmodium Species ◽  
Combination Therapies ◽  
Lead Compounds ◽  
Low Concentrations ◽  
Inhibitory Activities

Artemisinin-based combination therapies (ACT) are the frontline treatments against malaria worldwide. Recently the use of traditional infusions from Artemisia annua (from which artemisinin is obtained) or A. afra (lacking artemisinin) has been controversially advocated. Such unregulated plant-based remedies are strongly discouraged as they might constitute sub-optimal therapies and promote drug resistance. Here, we conducted the first comparative study of the anti-malarial effects of both plant infusions in vitro against the asexual erythrocytic stages of P. falciparum and the pre-erythrocytic (i. e., liver) stages of various Plasmodium species. Low concentrations of either infusion accounted for significant inhibitory activities across every parasite species and stage studied. We show that these antiplasmodial effects were essentially artemisinin-independent and were additionally monitored by observations of the parasite apicoplast and mitochondrion. In particular, the infusions significantly incapacitated sporozoites, and for P. vivax and P. cynomolgi, disrupted the hypnozoites. This provides the first indication that compounds other than 8- aminoquinolines could be effective antimalarials against relapsing parasites. These observations advocate for further screening to uncover urgently needed novel antimalarial lead compounds.

scholarly journals Artemisinin-independent inhibitory activity of Artemisia sp. infusions against different Plasmodium stages including relapse-causing hypnozoites

2021 ◽  
Vol 5 (3) ◽  
pp. e202101237
Author(s):  
Kutub Ashraf ◽  
Shahin Tajeri ◽  
Christophe-Sébastien Arnold ◽  
Nadia Amanzougaghene ◽  
Jean-François Franetich ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Inhibitory Activity ◽  
Parasite Species ◽  
Artemisia Annua ◽  
Combination Therapies ◽  
Lead Compounds ◽  
Low Concentrations ◽  
Inhibitory Activities

Artemisinin-based combination therapies (ACT) are the frontline treatments against malaria worldwide. Recently the use of traditional infusions from Artemisia annua (from which artemisinin is obtained) or Artemisia afra (lacking artemisinin) has been controversially advocated. Such unregulated plant-based remedies are strongly discouraged as they might constitute sub-optimal therapies and promote drug resistance. Here, we conducted the first comparative study of the anti-malarial effects of both plant infusions in vitro against the asexual erythrocytic stages of Plasmodium falciparum and the pre-erythrocytic (i.e., liver) stages of various Plasmodium species. Low concentrations of either infusion accounted for significant inhibitory activities across every parasite species and stage studied. We show that these antiplasmodial effects were essentially artemisinin-independent and were additionally monitored by observations of the parasite apicoplast and mitochondrion. In particular, the infusions significantly incapacitated sporozoites, and for Plasmodium vivax and P. cynomolgi, disrupted the hypnozoites. This provides the first indication that compounds other than 8-aminoquinolines could be effective antimalarials against relapsing parasites. These observations advocate for further screening to uncover urgently needed novel antimalarial lead compounds.

scholarly journals Evaluation of in vitro Anti-hyperglycemic Effect of Green Crab Hydrolysates Derived by Commercially Available Enzymes (P06-105-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Bouhee Kang ◽  
Angela Myracle ◽  
Denise Skonberg
Keyword(s):  
Inhibitory Activity ◽  
Unsaturated Fatty Acids ◽  
Carcinus Maenas ◽  
Primary Objective ◽  
Green Crab ◽  
Degree Of Hydrolysis ◽  
National Science Foundation Grant ◽  
Freeze Dried ◽  
Inhibitory Activities

Abstract Objectives Invasive green crabs (Carcinus maenas) have become well established in the U.S. over the past 100 years. Despite containing nutritionally important proteins, unsaturated fatty acids, and minerals, green crabs are not consumed due to their small size. A variety of peptides derived from muscle foods are known to have health benefits, and we hypothesized that high quality green crab proteins and their derivatives might have potential as carbohydrase inhibitors. Therefore, the primary objective of this study was to obtain anti-hyperglycemic peptides via enzymatic hydrolysis to develop commercial value of this unutilized crustacean. Methods Mechanically separated crab meat was homogenized with water (1:1), then hydrolyzed with 1% of Alcalase (AL, pH 8), Protamex (PR, pH 7), Flavourzyme (FL, pH 7), or Papain (PA, pH 6) for 60 min. Enzymes were thermally inactivated and then the hydrolysates were centrifuged to obtain the supernatant, then freeze-dried. Samples were processed in triplicate and then evaluated for degree of hydrolysis (DH) and α-glucosidase and α-amylase inhibitory activities. Significant (p < 0.05) differences in DH and carbohydrase inhibitory activities among treatments were determined by one-way ANOVA. Results Crab mince treated with AL exhibited the highest DH (18.3%), followed by PR (17.1%), FL (16.5%), and PA (15.8%). The PR treatment showed the highest α-glucosidase inhibitory activity (IC50 3.6 mg/mL) compared to other enzyme treatments (IC50 19.3–46.3 mg/mL) and the Control (IC50 22.3 mg/mL). The α-amylase inhibitory activity of PR (IC50 24.4 mg/mL) was lower than its α-glucosidase inhibitory activity. FL showed the highest α-amylase inhibitory activity (IC50 23.5 mg/mL) followed by PR, PA (IC50 34.8 mg/mL), AL (IC50 35.4 mg/mL), and Control (IC50 36.5 mg/mL) samples. Conclusions Our findings indicate that Protamex treatment has potential to derive carbohydrase inhibitory peptides from green crab and these peptides could be utilized as a health promoting ingredient in food products. In order to investigate changes in bioactivity due to human digestion, the hydrolysates will be utilized in a simulated digestion model and their bioactivity will be further evaluated. Funding Sources This study is supported by a National Science Foundation grant to Maine EPSCoR at the University of Maine.

Acetylcholinesterase inhibitory activity and neuroprotection in vitro, molecular docking, and improved learning and memory functions of demethylcurcumin in scopolamine-induced amnesia ICR mice

2020 ◽  
Vol 11 (3) ◽  
pp. 2328-2338 ◽  
Author(s):  
Yuh-Hwa Liu ◽  
Chia-Jung Lee ◽  
Liang-Chieh Chen ◽  
Tai-Lin Lee ◽  
Ying-Ying Hsieh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Learning And Memory ◽  
Inhibitory Activity ◽  
Proof Of Concept ◽  
Memory Functions ◽  
Icr Mice ◽  
Inhibitory Activities ◽  
Improved Learning ◽  
Concept Validation

Demethylcurcumin (DC) interventions improved learning and memory functions in scopolamine-induced amnesia ICR mice, providing the proof-of-concept validation of AChE inhibitory activities in vitro and molecular docking with AChE in silico.

scholarly journals Inhibitory Activities of Polyphenolic Extracts of Bangladeshi Vegetables against α-Amylase, α-Glucosidase, Pancreatic Lipase, Renin, and Angiotensin-Converting Enzyme

Foods ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 844
Author(s):  
Razia Sultana ◽  
Adeola M. Alashi ◽  
Khaleda Islam ◽  
Md Saifullah ◽  
C. Emdad Haque ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Pancreatic Lipase ◽  
Lipase Activity ◽  
Inhibitory Activity ◽  
The Other ◽  
Converting Enzyme ◽  
Inhibitory Activities ◽  
Ash Gourd ◽  
Better Than

The aim of the study was to determine the in vitro enzyme inhibition activities of aqueous polyphenolic extracts of nine popular Bangladeshi vegetables, namely ash gourd, bitter gourd, brinjal, Indian spinach, kangkong, okra, ridge gourd, snake gourd, and stem amaranth. Polyphenolic glycosides were the major compounds present in the extracts. Inhibition of α-amylase (up to 100% at 1 mg/mL) was stronger than α-glucosidase inhibition (up to 70.78% at 10 mg/mL). The Indian spinach extract was the strongest inhibitor of pancreatic lipase activity (IC50 = 276.77 µg/mL), which was significantly better than that of orlistat (381.16 µg/mL), a drug. Ash gourd (76.51%), brinjal (72.48%), and snake gourd (66.82%) extracts were the most effective inhibitors of angiotensin-converting enzyme (ACE), an enzyme whose excessive activities have been associated with hypertension. Brinjal also had a significantly higher renin-inhibitory activity than the other vegetable extracts. We conclude that the vegetable extracts may have the ability to reduce enzyme activities that have been associated with hyperglycemia, hyperlipidemia, and hypertension.

scholarly journals Novel Heteroaryl Selenocyanates and Diselenides as Potent Antileishmanial Agents

2016 ◽  
Vol 60 (6) ◽  
pp. 3802-3812 ◽  
Author(s):  
Ylenia Baquedano ◽  
Verónica Alcolea ◽  
Miguel Ángel Toro ◽  
Killian Jesús Gutiérrez ◽  
Paul Nguewa ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Inhibitory Activity ◽  
Leishmania Infantum ◽  
Trypanothione Reductase ◽  
Content Type ◽  
Bioactive Scaffolds ◽  
Lead Compounds ◽  
Novel Structures ◽  
Micromolar Range

A series of new selenocyanates and diselenides bearing interesting bioactive scaffolds (quinoline, quinoxaline, acridine, chromene, furane, isosazole, etc.) was synthesized, and theirin vitroleishmanicidal activities againstLeishmania infantumamastigotes along with their cytotoxicities in human THP-1 cells were determined. Interestingly, most tested compounds were active in the low micromolar range and led us to identify four lead compounds (1h, 2d, 2e, and 2f) with 50% effective dose (ED50) values ranging from 0.45 to 1.27 μM and selectivity indexes of >25 for all of them, much higher than those observed for the reference drugs. These active derivatives were evaluated against infected macrophages, and in order to gain preliminary knowledge about their possible mechanism of action, the inhibition of trypanothione reductase (TryR) was measured. Among these novel structures, compounds 1h (3,5-dimethyl-4-isoxazolyl selenocyanate) and 2d [3,3′-(diselenodiyldimethanediyl)bis(2-bromothiophene)] exhibited good association between TryR inhibitory activity and antileishmanial potency, pointing to 1h, for its excellent theoretical ADME (absorption, distribution, metabolism, and excretion) properties, as the most promising lead molecule for leishmancidal drug design.

scholarly journals Docking Characterization and in vitro Inhibitory Activity of Flavan-3-ols and Dimeric Proanthocyanidins Against the Main Protease Activity of SARS-Cov-2

2020 ◽  
Vol 11 ◽  
Author(s):  
Yue Zhu ◽  
De-Yu Xie
Keyword(s):  
Hydrogen Bonds ◽  
Inhibitory Activity ◽  
Docking Simulation ◽  
Binding Pocket ◽  
Structural Features ◽  
The Other ◽  
Main Protease ◽  
Inhibitory Activities ◽  
The One

We report to use the main protease (Mpro) of SARS-Cov-2 to screen plant flavan-3-ols and proanthocyanidins. Twelve compounds, (–)-afzelechin (AF), (–)-epiafzelechin (EAF), (+)-catechin (CA), (–)-epicatechin (EC), (+)-gallocatechin (GC), (–)-epigallocatechin (EGC), (+)-catechin-3-O-gallate (CAG), (–)-epicatechin-3-O-gallate (ECG), (–)-gallocatechin-3-O-gallate (GCG), (–)-epigallocatechin-3-O-gallate (EGCG), procyanidin A2 (PA2), and procyanidin B2 (PB2), were selected for docking simulation. The resulting data predicted that all 12 metabolites could bind to Mpro. The affinity scores of PA2 and PB2 were predicted to be −9.2, followed by ECG, GCG, EGCG, and CAG, −8.3 to −8.7, and then six flavan-3-ol aglycones, −7.0 to −7.7. Docking characterization predicted that these compounds bound to three or four subsites (S1, S1′, S2, and S4) in the binding pocket of Mpro via different spatial ways and various formation of one to four hydrogen bonds. In vitro analysis with 10 available compounds showed that CAG, ECG, GCG, EGCG, and PB2 inhibited the Mpro activity with an IC50 value, 2.98 ± 0.21, 5.21 ± 0.5, 6.38 ± 0.5, 7.51 ± 0.21, and 75.3 ± 1.29 μM, respectively, while CA, EC, EGC, GC, and PA2 did not have inhibitory activities. To further substantiate the inhibitory activities, extracts prepared from green tea (GT), two muscadine grapes (MG), cacao, and dark chocolate (DC), which are rich in CAG, ECG, GAG, EGCG, or/and PB2, were used for inhibitory assay. The resulting data showed that GT, two MG, cacao, and DC extracts inhibited the Mpro activity with an IC50 value, 2.84 ± 0.25, 29.54 ± 0.41, 29.93 ± 0.83, 153.3 ± 47.3, and 256.39 ± 66.3 μg/ml, respectively. These findings indicate that on the one hand, the structural features of flavan-3-ols are closely associated with the affinity scores; on the other hand, the galloylation and oligomeric types of flavan-3-ols are critical in creating the inhibitory activity against the Mpro activity.

Angiotensin I Converting Enzyme–Inhibitory Activity of Bovine, Ovine, and Caprine κ-Casein Macropeptides and Their Tryptic Hydrolysates

2003 ◽  
Vol 66 (9) ◽  
pp. 1686-1692 ◽  
Author(s):  
M. A. MANSO ◽  
R. LÓPEZ-FANDIÑO
Keyword(s):  
Inhibitory Activity ◽  
Converting Enzyme ◽  
Gastrointestinal Digestion ◽  
Ace Inhibitory Activity ◽  
Angiotensin I Converting Enzyme ◽  
Gastrointestinal Conditions ◽  
Tryptic Hydrolysate ◽  
Inhibitory Activities ◽  
Ace Inhibitory

This work evaluated the angiotensin-converting enzyme (ACE)–inhibitory activities of bovine, ovine, and caprine κ-casein macropeptides (CMPs) and their tryptic hydrolysates. The results obtained indicate that bovine, ovine, and caprine CMPs exhibited moderate in vitro ACE-inhibitory activities that increased considerably after digestion under simulated gastrointestinal conditions. Active peptides could also be produced from CMPs via proteolysis with trypsin, with tryptic hydrolysates exhibiting a more extensive ACE-inhibitory activity than intact CMPs during simulated gastrointestinal digestion. Two active fractions were chromatographically separated from the tryptic hydrolysate of the bovine CMP, but their complexity hampered the assignment of the ACE-inhibitory activity to specific peptide sequences. Evidence for the release of the strong ACE-inhibitory tripeptide IPP was found upon simulation of the gastrointestinal digestion of peptides released by trypsin from the CMP sequence. These findings might help to promote further exploitation of cheese whey in the preparation of nutraceuticals for inclusion in the composition of functional food products with high added values.

scholarly journals Synthesis, In Silico and In Vitro Evaluation of Some Flavone Derivatives for Acetylcholinesterase and BACE-1 Inhibitory Activity

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4064
Author(s):  
Thai-Son Tran ◽  
Thanh-Dao Tran ◽  
The-Huan Tran ◽  
Thanh-Tan Mai ◽  
Ngoc-Le Nguyen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Biological Effects ◽  
Novel Therapies ◽  
Dual Action ◽  
Flavone Derivatives ◽  
Inhibitory Activities ◽  
High Yields ◽  
Bace 1

Acetylcholinesterase (AChE) and β-secretase (BACE-1) have become attractive therapeutic targets for Alzheimer’s disease (AD). Flavones are flavonoid derivatives with various bioactive effects, including AChE and BACE-1 inhibition. In the present work, a series of 14 flavone derivatives was synthesized in relatively high yields (35–85%). Six of the synthetic flavones (B4, B5, B6, B8, D6 and D7) had completely new structures. The AChE and BACE-1 inhibitory activities were tested, giving pIC50 3.47–4.59 (AChE) and 4.15–5.80 (BACE-1). Three compounds (B3, D5 and D6) exhibited the highest biological effects on both AChE and BACE-1. A molecular docking investigation was conducted to explain the experimental results. These molecules could be employed for further studies to discover new structures with dual action on both AChE and BACE-1 that could serve as novel therapies for AD.

scholarly journals Synthesis and In Vitro Inhibition Effect of New Pyrido[2,3-d]pyrimidine Derivatives on Erythrocyte Carbonic Anhydrase I and II

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Hilal Kuday ◽  
Fatih Sonmez ◽  
Cigdem Bilen ◽  
Emre Yavuz ◽  
Nahit Gençer ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Inhibitory Activity ◽  
Pyrimidine Derivatives ◽  
Structure Activity ◽  
Carbonic Anhydrase I ◽  
Activity Structure ◽  
In Vitro Inhibition ◽  
Inhibitory Activities ◽  
Erythrocyte Carbonic Anhydrase

In vitro inhibition effects of indolylchalcones and new pyrido[2,3-d]pyrimidine derivatives on purified human carbonic anhydrase I and II (hCA I and II) were investigated by using CO2as a substrate. The results showed that all compounds inhibited the hCA I and hCA II enzyme activities. Among all the synthesized compounds,7e(IC50=6.79 µM) was found to be the most active compound for hCA I inhibitory activity and5g(IC50=7.22 µM) showed the highest hCA II inhibitory activity. Structure-activity relationships study showed that indolylchalcone derivatives have higher inhibitory activities than pyrido[2,3-d]pyrimidine derivatives on hCA I and hCA II. Additionally, methyl group bonded to uracil ring increases inhibitory activities on both hCA I and hCA II.

scholarly journals Metabolomic Profiling of the Malaria Box Reveals Antimalarial Target Pathways

2016 ◽  
Vol 60 (11) ◽  
pp. 6635-6649 ◽  
Author(s):  
Erik L. Allman ◽  
Heather J. Painter ◽  
Jasmeet Samra ◽  
Manuela Carrasquilla ◽  
Manuel Llinás
Keyword(s):  
High Performance ◽  
Parasite Species ◽  
Metabolic Effects ◽  
Content Type ◽  
Lead Compounds ◽  
Metabolomic Profiling ◽  
Metabolic Disruption ◽  
Malaria Box ◽  
Selection Of

ABSTRACTThe threat of widespread drug resistance to frontline antimalarials has renewed the urgency for identifying inexpensive chemotherapeutic compounds that are effective againstPlasmodium falciparum, the parasite species responsible for the greatest number of malaria-related deaths worldwide. To aid in the fight against malaria, a recent extensive screening campaign has generated thousands of lead compounds with low micromolar activity against blood stage parasites. A subset of these leads has been compiled by the Medicines for Malaria Venture (MMV) into a collection of structurally diverse compounds known as the MMV Malaria Box. Currently, little is known regarding the activity of these Malaria Box compounds on parasite metabolism during intraerythrocytic development, and a majority of the targets for these drugs have yet to be defined. Here we interrogated thein vitrometabolic effects of 189 drugs (including 169 of the drug-like compounds from the Malaria Box) using ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). The resulting metabolic fingerprints provide information on the parasite biochemical pathways affected by pharmacologic intervention and offer a critical blueprint for selecting and advancing lead compounds as next-generation antimalarial drugs. Our results reveal several major classes of metabolic disruption, which allow us to predict the mode of action (MoA) for many of the Malaria Box compounds. We anticipate that future combination therapies will be greatly informed by these results, allowing for the selection of appropriate drug combinations that simultaneously target multiple metabolic pathways, with the aim of eliminating malaria and forestalling the expansion of drug-resistant parasites in the field.

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