Novel hybrids of oxoisoaporphine-tryptamine as acetylcholinesterase-induced β-amyloid aggregation inhibitors with improved antioxidant properties

A series of dual binding site acetylcholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their antioxidant ability and inhibitory potency on AChE and AChE-induced b-amyloid (Ab) aggregation. The new hybrids consist of a unit of 1-azabenzanthrone and a tryptamine or its derivative, connected through a a,w - alkyldiamide bridge. These hybrids exhibit moderate AChE inhibitory activity with IC50 values in the micromolar range and significant in vitro inhibitory activity toward the AChE-induced Ab aggregation. Moreover, six out of the nine hybrids of this series exhibit a higher oxygen radical absorbance capacity than trolox, which makes them promising anti-Alzheimer drug candidates.

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The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

Viruses ◽

10.3390/v13050873 ◽

2021 ◽

Vol 13 (5) ◽

pp. 873

Author(s):

Raphael J. Eberle ◽

Danilo S. Olivier ◽

Marcos S. Amaral ◽

Ian Gering ◽

Dieter Willbold ◽

...

Keyword(s):

Binding Mode ◽

Drug Candidates ◽

Main Protease ◽

Ic50 Values ◽

Repurposed Drugs ◽

Antiparasitic Drugs ◽

Inhibitory Potential ◽

Dynamics Simulations ◽

Micromolar Range

Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CLpro but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.

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Fine-Tuning the Biological Profile of Multitarget Mitochondriotropic Antioxidants for Neurodegenerative Diseases

Antioxidants ◽

10.3390/antiox10020329 ◽

2021 ◽

Vol 10 (2) ◽

pp. 329

Author(s):

Daniel Chavarria ◽

Ophelie Da Silva ◽

Sofia Benfeito ◽

Sandra Barreiro ◽

Jorge Garrido ◽

...

Keyword(s):

Inhibitory Activity ◽

Antioxidant Properties ◽

Neuroblastoma Cells ◽

Oxidation Potential ◽

Fine Tuning ◽

Mitochondrial Oxidative Stress ◽

Electric Eel ◽

Ic50 Values ◽

System Extension ◽

Inhibition Potency

Neurotransmitter depletion and mitochondrial dysfunction are among the multiple pathological events that lead to neurodegeneration. Following our previous studies related with the development of multitarget mitochondriotropic antioxidants, this study aims to evaluate whether the π-system extension on the chemical scaffolds of AntiOXCIN2 and AntiOXCIN3 affects their bioactivity and safety profiles. After the synthesis of four triphenylphosphonium (TPP+) conjugates (compounds 2–5), we evaluated their antioxidant properties and their effect on neurotransmitter-metabolizing enzymes. All compounds were potent equine butyrylcholinesterase (eqBChE) and moderate electric eel acetylcholinesterase (eeAChE) inhibitors, with catechols 4 and 5 presenting lower IC50 values than AntiOXCIN2 and AntiOXCIN3, respectively. However, differences in the inhibition potency and selectivity of compounds 2–5 towards non-human and human cholinesterases (ChEs) were observed. Co-crystallization studies with compounds 2–5 in complex with human ChEs (hChEs) showed that these compounds exhibit different binging modes to hAChE and hBChE. Unlike AntiOXCINs, compounds 2–5 displayed moderate human monoamine oxidase (hMAO) inhibitory activity. Moreover, compounds 4 and 5 presented higher ORAC-FL indexes and lower oxidation potential values than the corresponding AntiOXCINs. Catechols 4 and 5 exhibited broader safety windows in differentiated neuroblastoma cells than benzodioxole derivatives 2 and 3. Compound 4 is highlighted as a safe mitochondria-targeted antioxidant with dual ChE/MAO inhibitory activity. Overall, this work is a contribution for the development of dual therapeutic agents addressing both mitochondrial oxidative stress and neurotransmitter depletion.

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In Vitro Antimicrobial, Antioxidant and Anticancer Activities of Egyptian Citrus Beebread

Molecules ◽

10.3390/molecules26092433 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2433

Author(s):

Nesren Elsayed ◽

Hatem Sharaf El-Din ◽

Ammar B. Altemimi ◽

Hanaa Y. Ahmed ◽

Anubhav Pratap-Singh ◽

...

Keyword(s):

Fatty Acids ◽

Inhibitory Activity ◽

Nutritive Value ◽

Antioxidant Properties ◽

Antitumor Agent ◽

Monounsaturated Fatty Acids ◽

Free Sugar ◽

Natural Food ◽

Anticancer Activities

In this study, Egyptian beebread (EBB) was investigated for its nutritive value, chemical composition, antioxidant properties, antimicrobial and antitumor activities. Results indicated that EBB was a good source of protein (23.58 ± 0.183 g/100 g BB), total free sugar (20.266 ± 0.930) and potassium (290.202 ± 2.645 mg/100 g). Additionally, 14 fatty acids were identified in EBB, wherein polyunsaturated and monounsaturated fatty acids represented 51.06% ± 0.09% and 9.86% ± 0.01%, respectively. The EBB extract exhibited almost 400% better antiradical activity than BHT, with IC50 of EBB extract being 10.7 µg/mL compared to 39.5 µg/mL for BHT. EBB exhibited higher inhibitory activity than the reference compound against Staphylococcus aureus and Escherichia coli, followed by Bacillus subtilis. No inhibitory activity was observed against Aspergillus Niger. Additionally, the highest inhibitory activity was recorded against Caco-2 cells, followed by PC3 and HepG-2 cancer cell lines with IC50 values 262, 314 and 386 μg/mL, respectively. These findings establish the potential of EBB as an antioxidant, antimicrobial and antitumor agent, with possible applications as natural food supplements and natural preservatives.

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Mammalian Arginase Inhibitory Activity of Methanolic Extracts and Isolated Compounds from Cyperus Species

Molecules ◽

10.3390/molecules26061694 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1694

Author(s):

Kamel Arraki ◽

Perle Totoson ◽

Alain Decendit ◽

Andy Zedet ◽

Justine Maroilley ◽

...

Keyword(s):

Inhibitory Activity ◽

Methanolic Extract ◽

Significant Inhibition ◽

Isolation And Identification ◽

Vasorelaxant Effect ◽

Methanolic Extracts ◽

Phytochemical Investigation ◽

Ic50 Values ◽

First Time

Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (1–2), together with three other stilbenes, trans-resveratrol (3), trans-scirpusin A (4), trans-cyperusphenol A (6), and two flavonoids, aureusidin (5) and luteolin (7), which were isolated for the first time from C.thunbergii and C. glomeratus. Structures were established on the basis of the spectroscopic data from MS and NMR experiments. The arginase inhibitory activity of compounds 1–7 was evaluated through an in vitro arginase inhibitory assay using purified liver bovine arginase. As a result, five compounds (1, 4–7) showed significant inhibition of arginase, with IC50 values between 17.6 and 60.6 µM, in the range of those of the natural arginase inhibitor piceatannol (12.6 µM). In addition, methanolic extract from Cyperus thunbergii exhibited an endothelium and NO-dependent vasorelaxant effect on thoracic aortic rings from rats and improved endothelial dysfunction in an adjuvant-induced arthritis rat model.

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In vitro Antidiabetic, anti-obesity and antioxidant proprities of Rosemary extracts

JOURNAL OF ADVANCES IN CHEMISTRY ◽

10.24297/jac.v10i2.5497 ◽

2014 ◽

Vol 10 (2) ◽

pp. 2305-2316 ◽

Cited By ~ 4

Author(s):

Manel Ben Ali ◽

Kais Mnafgui ◽

Abdelfattah Feki ◽

Mohamed Damak ◽

Noureddine Allouche

Keyword(s):

Essential Oil ◽

Ethyl Acetate ◽

Pancreatic Lipase ◽

Antioxidant Properties ◽

Methanolic Extracts ◽

Ic50 Values ◽

Inhibitory Potential ◽

Prevention Of Diabetes ◽

First Time

Diabetes mellitus is a serious health problem worldwide that has adverse and long-lasting consequences for individuals, families, and communities. Hence, this study sought to investigate the inhibitory potential of rosemary extracts on key-enzymes related to diabetes such as α-amylase and pancreatic lipase activities, as well as to assess their antioxidant properties in vitro. The IC50 values of Rosemary essential oil, ethyl acetate and methanolic extracts against α-amylase were 28.36, 34.11 and 30.39 µg/mL respectively, and those against pancreatic lipase were 32.25, 36.64 and 34.07 µg/mL, suggesting strong anti-diabetic and anti-obesity effects of Rosemary. The methanolic extract was found to be the highest in levels of phenolic (282.98 µgGAE/mg extract) and flavonoids (161.05 µg QE /mg extract) contents as well as in the antioxidant activity (IC50 = 15.82 µg/mL) as compared to other extracts ethyl acetate (IC50 = 32.23 µg/mL) and essential oil (IC50 = 96.12 µg/mL).Antioxidant efficacy of Rosemary extracts has been estimated in the stabilization of sunflower oil (SFO) at three different concentrations, i.e. 200 (SFO-200), 500 (SFO-500) and 1000 ppm (SFO-1000). Results showed the highest efficiency of SFO-1000.The results obtained in this study demonstrated for the first time that Rosemary is a potent source of natural inhibitors of α-amylase and pancreatic lipase with powerful antioxidants proprieties that might be used in the food stabilization and the prevention of diabetes and obesity complications as a complementary pharmacological drug.

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Aktivitas Penghambatan Xantin Oksidase pada Ekstrak Daun Sirih Hitam (Piper sp)

Proceeding of Mulawarman Pharmaceuticals Conferences ◽

10.25026/mpc.v3i2.102 ◽

2016 ◽

Vol 3 ◽

pp. 160-163

Author(s):

Muhammad Amir Masruhim ◽

Wisnu Cahyo Prabowo ◽

Dita Paramitha

Keyword(s):

Uric Acid ◽

Xanthine Oxidase ◽

Inhibitory Activity ◽

Ethanol Extract ◽

Betel Leaf ◽

Activity Test ◽

Ic50 Values ◽

One Way Anova

Hyperuricemia is a condition in which increased levels of uric acid in the blood. Xanthine oxidase role in the oxidation of hypoxanthine and xanthine to uric acid. One treatment of hyperuricemia is inhibiting xanthine oxidase in the process of formation of uric acid. The purpose of this study to determine the inhibitory activity of xanthine oxidase in the ethanol extract of black betel leaf (Piper sp). Xanthine oxidase inhibitory activity test using UV-Vis spectrophotometry in vitro with a concentration of 5 ppm, 10 ppm and 20 ppm. The data obtained were analyzed using one-way ANOVA. The result is the ethanol extract of black betel leaf has a different activity significantly and IC50 values obtained is 65.96 ppm.

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Sesquiterpenes and a monoterpenoid with acetylcholinesterase (AchE) inhibitory activity from Valeriana officinalis var. latiofolia in vitro and in vivo

Fitoterapia ◽

10.1016/j.fitote.2016.03.011 ◽

2016 ◽

Vol 110 ◽

pp. 142-149 ◽

Cited By ~ 13

Author(s):

Heng-Wen Chen ◽

Xuan-Hui He ◽

Rong Yuan ◽

Ben-Jun Wei ◽

Zhong Chen ◽

...

Keyword(s):

Inhibitory Activity ◽

Valeriana Officinalis ◽

Ache Inhibitory Activity

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Inhibitory activity of stilbenes on Alzheimer’s β-amyloid fibrils in vitro

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2006.09.069 ◽

2007 ◽

Vol 15 (2) ◽

pp. 1160-1167 ◽

Cited By ~ 152

Author(s):

Céline Rivière ◽

Tristan Richard ◽

Lysiane Quentin ◽

Stéphanie Krisa ◽

Jean-Michel Mérillon ◽

...

Keyword(s):

Inhibitory Activity ◽

Amyloid Fibrils ◽

Β Amyloid

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EVALUATION OF IN VITRO ANTIOXIDANT AND α-AMYLASE INHIBITORY ACTIVITY OF PHYLLANTHUS INDOFISCHERI BENNET

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i11.14013 ◽

2016 ◽

Vol 8 (11) ◽

pp. 131 ◽

Cited By ~ 1

Author(s):

Kalpana S ◽

Ramakrushna B. ◽

Anitha S.

Keyword(s):

Inhibitory Activity ◽

Colorimetric Method ◽

Radical Scavenging ◽

Total Flavonoid ◽

Aluminium Chloride ◽

Total Phenolic ◽

Total Flavonoid Content ◽

Flavonoid Content ◽

Ic50 Values

Objective: The present study evaluates the antioxidant and α-amylase inhibitory activity of leaf and bark extracts of Phyllanthus indofischeri with methanol and water as solvents. In addition to this, the total phenolic content and total flavonoid content was determined.Methods: The total phenolic and total flavonoid content of the extracts was determined by folin ciocaletus reagent method and aluminium chloride colorimetric method respectively. The antioxidant and α-amylase inhibitory activity were measured by various assays, including α, α-diphenyl-ẞ-dipicryl-hydrazyl (DPPH) free radical scavenging, 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) radical scavenging, superoxide radical scavenging, total antioxidant capacity by phosphomolybdate method and porcine pancreatic α-amylase inhibitory assay. The IC50 values were calculated and compared with standards such as gallic acid, ascorbic acid and α-acarbose.Results: The results illustrated that all the extracts of Phyllanthus indofischeri exhibit significant antioxidant and α-amylase inhibitory activity. Among the extracts, methanolic leaf extract showed high levels of activity followed by bark water extract.Conclusion: Phyllanthus indofischeri extracts had shown antioxidant and α-amylase inhibitory activity. On the basis of these results, Phyllanthus indofischeri can be used as a natural antioxidant and hypoglycemic agent against various disorders related to oxidative stress; and the isolation of bioactive compounds was warranted.

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Antioxidant Properties and Digestive Enzyme Inhibitory Activity of the Aqueous Extract from Leafy Stems of Cissus polyantha

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/7384532 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Mahamad Abba Talba ◽

David Miaffo ◽

Sylviane Laure Poualeu Kamani ◽

Albert Kamanyi ◽

Sylvie Léa Wansi

Keyword(s):

Traditional Medicine ◽

Aqueous Extract ◽

Inhibitory Activity ◽

Antiradical Activity ◽

Digestive Enzyme ◽

Antioxidant Properties ◽

Antioxidant Potential ◽

Antioxidant Power ◽

Treatment Of Diabetes

Cissus polyantha (Vitaceae) is a plant used in Cameroonian traditional medicine for the treatment of diabetes. The aims of this study were to evaluate the in vitro antioxidant and antidiabetic activities of the aqueous extract of Cissus polyantha leafy stems. The enzyme inhibitory activity was determined in vitro on α-amylase and α-glucosidase enzymes, followed by confirmative study in vivo on normal rats (oral starch and sucrose tolerance tests at doses of 111, 222, and 444 mg/kg). The ferric reducing antioxidant power and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) antiradical activity of the extract were examined to evaluate the antioxidant potential of the extract. The total content of phenols, flavonoids, and tannins of the extract were also determined. The results showed an inhibitory effect of the extract on the α-amylase and α-glucosidase activities with IC50 values of 216.14 and 182.40 μg/mL, respectively. The extract at doses of 222 and 444 mg/kg induced a significant decrease in postprandial glycaemia during the starch and sucrose tolerance tests. A remarkable antiradical activity of the extract was obtained although lower than that of the standard product. The aqueous extract of leafy stems of Cissus polyantha has an interesting inhibitory activity on the α-amylase and α-glucosidase enzymes, as well as an antioxidant potential, thus validating its use in traditional medicine for the treatment of diabetes mellitus and its complications.

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