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 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 Bioactivity-guided separation of potential α-glycosidase inhibitor from clerodendranthus spicatus based on HSCCC coupled with molecular docking

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunsheng Zhu ◽  
Hongjuan Niu ◽  
Anzheng Nie ◽  
Meng Bian
Keyword(s):  
Molecular Docking ◽  
Tartaric Acid ◽  
Inhibitory Activity ◽  
High Speed ◽  
Edible Plant ◽  
Glycosidase Inhibitor ◽  
Hypoglycemic Drug ◽  
Inhibitory Activities ◽  
Counter Current

AbstractClerodendranthus Spicatus is a traditional Dais medi-edible plant and it has been proven to have good blood glucose-lowering efficacy. However, the material basis of Clerodendranthus Spicatus has not been clarified yet and therefore needs to be determined. In this paper, the effective ingredients of this medicine were purified by high-speed counter-current chromatography. Alongside, their potential hypoglycemic activity was determined by α-glucosidase inhibitory activities in vitro and molecular docking. Finally, five compounds were purified and identified as 2-caffeoyl-L-tartaric acid (1), N-(E)-caffeoyldopamine (2), rosmarinc acid (3), methyl rosmarinate (4), 6,7,8,3′,4′-Pentamethoxyflavone (5). Examination of α-glucosidase inhibitory activity in vitro showed that 2-caffeoyl-L-tartaric acid and rosmarinic acid had a higher inhibitory activity than acarbose. Molecular docking indicated that the affinity energy of the identified compounds ranged from − 7.6 to − 8.6 kcal/mol, a more desirable result than acarbose (− 6.6 kcal/mol). Particularly, rosmarinc acid with the lowest affinity energy of − 8.6 kcal/mol was wrapped with 6 hydrogen bonds. Overall, α-glucosidase inhibitory activities and molecular docking suggested that rosmarinc acid was likely to be a promising hypoglycemic drug.

Design, Synthesis, Molecular Docking and Biological Evaluation of 1-(benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol Derivatives as Antiproliferative Agents

2019 ◽  
Vol 16 (10) ◽  
pp. 837-845
Author(s):  
Sandhya Jonnala ◽  
Bhaskar Nameta ◽  
Murthy Chavali ◽  
Rajashaker Bantu ◽  
Pallavi Choudante ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Mouse Skin ◽  
Coupling Reaction ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

scholarly journals Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fariba Peytam ◽  
Ghazaleh Takalloobanafshi ◽  
Toktam Saadattalab ◽  
Maryam Norouzbahari ◽  
Zahra Emamgholipour ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Rat Small Intestine ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Mild Conditions ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document