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.

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 for Acetylcholinesterase and BACE-1 Inhibitory Activity of Some N-Substituted-4-Phenothiazine-Chalcones

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3916
Author(s):  
Thai-Son Tran ◽  
Minh-Tri Le ◽  
Thi-Cam-Vi Nguyen ◽  
The-Huan Tran ◽  
Thanh-Dao Tran ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Biological Activities ◽  
Quantitative Structure Activity Relationship ◽  
2D Qsar ◽  
Study Results ◽  
High Yields ◽  
In Silico Models ◽  
Bace 1

Acetylcholinesterase (AChE) and beta-secretase (BACE-1) are two attractive targets in the discovery of novel substances that could control multiple aspects of Alzheimer’s disease (AD). Chalcones are the flavonoid derivatives with diverse bioactivities, including AChE and BACE-1 inhibition. In this study, a series of N-substituted-4-phenothiazine-chalcones was synthesized and tested for AChE and BACE-1 inhibitory activities. In silico models, including two-dimensional quantitative structure–activity relationship (2D-QSAR) for AChE and BACE-1 inhibitors, and molecular docking investigation, were developed to elucidate the experimental process. The results indicated that 13 chalcone derivatives were synthesized with relatively high yields (39–81%). The bioactivities of these substances were examined with pIC50 3.73–5.96 (AChE) and 5.20–6.81 (BACE-1). Eleven of synthesized chalcones had completely new structures. Two substances AC4 and AC12 exhibited the highest biological activities on both AChE and BACE-1. These substances could be employed for further researches. In addition to this, the present study results suggested that, by using a combination of two types of predictive models, 2D-QSAR and molecular docking, it was possible to estimate the biological activities of the prepared compounds with relatively high accuracy.

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.

Synthesis, Molecular Docking, and In Vitro Investigation of 1,1'-Diaryl- 3,3'-(p-phenylenedicarbonyl) dithioureas as Urease Inhibitors

2020 ◽  
Vol 17 (4) ◽  
pp. 254-259
Author(s):  
Hummera Rafique ◽  
Fizza Tahira ◽  
Syeda Zar Afshan ◽  
Muhammad Naseem ◽  
Naghmana Kausar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Mode ◽  
Docking Studies ◽  
Inhibitor Binding ◽  
In Vitro Investigation ◽  
Urease Enzyme ◽  
Inhibitory Activities ◽  
Urease Inhibitory ◽  
High Yields

Synthesis of some 1,1'-diaryl-3,3'-(p-phenylenedicarbonyl)dithioureas was accomplished in two steps. Dithioureas were prepared under inert conditions with significantly high yields. Inhibitory activity of dithiourea compounds was investigated against urease enzyme. All the synthesized compounds were evaluated for their urease inhibitory activities, and molecular docking studies were carried out to ascertain the inhibitor binding mode with the enzyme. All the compounds displayed moderate to significant urease inhibitory activities.

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 Monoclonal antibodies specific to a Ca2+-bound form of lipocortin I distinguish its Ca2+-dependent phospholipid-binding ability from its ability to inhibit phospholipase A2

1990 ◽  
Vol 269 (3) ◽  
pp. 709-715 ◽  
Author(s):  
H Hayashi ◽  
M K Owada ◽  
S Sonobe ◽  
K Domae ◽  
T Yamanouchi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Phospholipase A2 ◽  
Inhibitory Activity ◽  
Biological Effects ◽  
Free Form ◽  
E Coli ◽  
Phospholipid Binding ◽  
Ef Hand

Lipocortin I, a Ca2(+)-and phospholipid-binding protein without EF-hand structures, has many biological effects in vitro. Its actual role in vivo, however is unknown. We obtained and characterized five monoclonal antibodies to lipocortin I. Two of these monoclonal antibodies (L2 and L4-MAbs) reacted with the Ca(+)-bound form of lipocortin I, but not with the Ca2(+)-free form, both in vivo and in vitro. Lipocortin I required greater than or equal to 10 microM-Ca2+ to bind the two antibodies, and this Ca2+ requirement was not affected by phosphatidylserine. L2-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I and inhibited its binding to Escherichia coli membranes and to phosphatidylserine in vitro. L4-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I, but did not affect its binding to E. coli membranes or to phosphatidylserine. These findings indicated that the inhibition of phospholipase A2 by lipocortin I was not simply due to removal or capping of the substrates in E. coli membranes. Furthermore, an immunofluorescence study using L2-MAb showed the actual existence of Ca2(+)-bound form of lipocortin I in vivo.

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.

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