scholarly journals Efficient Electrocatalytic Approach to Spiro[Furo[3,2-b]pyran-2,5′-pyrimidine] Scaffold as Inhibitor of Aldose Reductase

Electrochem ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 295-310
Author(s):  
Michail N. Elinson ◽  
Anatoly N. Vereshchagin ◽  
Yuliya E. Ryzhkova ◽  
Fedor V. Ryzhkov ◽  
Artem N. Fakhrutdinov ◽  
...  
Keyword(s):  
Aldose Reductase ◽  
Scoring Function ◽  
Binding Pocket ◽  
Cascade Reactions ◽  
Sodium Halides ◽  
New Type ◽  
Treatment Of Diabetes ◽  
Synthetic Methodologies ◽  
Pharmacologically Active ◽  
Electrochemical Cyclization

A continuously growing interest in convenient and ‘green’ reaction techniques encourages organic chemists to elaborate on new synthetic methodologies. Nowadays, organic electrochemistry is a new useful method with important synthetic and ecological advantages. The employment of an electrocatalytic methodology in cascade reactions is very promising because it provides the combination of the synthetic virtues of the cascade strategy with the ecological benefits and convenience of electrocatalytic procedures. In this research, a new type of the electrocatalytic cascade transformation was found: the electrochemical cyclization of 1,3-dimethyl-5-[[3-hydroxy-6-(hydroxymethyl)-4-oxo-4H-pyran-2-yl](aryl)methyl]pyrimidine-2,4,6(1H,3H,5H)-triones was carried out in alcohols in an undivided cell in the presence of sodium halides with the selective formation of spiro[furo[3,2-b]pyran-2,5′-pyrimidines] in 59-95% yields. This new electrocatalytic process is a selective, facile, and efficient way to create spiro[furo[3,2-b]pyran-2,5′-pyrimidines], which are pharmacologically active heterocyclic systems with different biomedical applications. Spiro[furo[3,2-b]pyran-2,5′-pyrimidines] were found to occupy the binding pocket of aldose reductase and inhibit it. The values of the binding energy and Lead Finder’s Virtual Screening scoring function showed that the formation of protein–ligand complexes was favorable. The synthesized compounds are promising for the inhibition of aldose reductase. This makes them interesting for study in the treatment of diabetes or similar diseases.

scholarly journals GNINA 1.0: molecular docking with deep learning

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Andrew T. McNutt ◽  
Paul Francoeur ◽  
Rishal Aggarwal ◽  
Tomohide Masuda ◽  
Rocco Meli ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Root Mean Square ◽  
Root Mean Square Deviation ◽  
Computational Cost ◽  
Scoring Function ◽  
Binding Pocket ◽  
Protein Docking ◽  
Mean Square ◽  
Mean Square Deviation ◽  
Autodock Vina

AbstractMolecular docking computationally predicts the conformation of a small molecule when binding to a receptor. Scoring functions are a vital piece of any molecular docking pipeline as they determine the fitness of sampled poses. Here we describe and evaluate the 1.0 release of the Gnina docking software, which utilizes an ensemble of convolutional neural networks (CNNs) as a scoring function. We also explore an array of parameter values for Gnina 1.0 to optimize docking performance and computational cost. Docking performance, as evaluated by the percentage of targets where the top pose is better than 2Å root mean square deviation (Top1), is compared to AutoDock Vina scoring when utilizing explicitly defined binding pockets or whole protein docking. Gnina, utilizing a CNN scoring function to rescore the output poses, outperforms AutoDock Vina scoring on redocking and cross-docking tasks when the binding pocket is defined (Top1 increases from 58% to 73% and from 27% to 37%, respectively) and when the whole protein defines the binding pocket (Top1 increases from 31% to 38% and from 12% to 16%, respectively). The derived ensemble of CNNs generalizes to unseen proteins and ligands and produces scores that correlate well with the root mean square deviation to the known binding pose. We provide the 1.0 version of Gnina under an open source license for use as a molecular docking tool at https://github.com/gnina/gnina.

scholarly journals GNINA 1.0: Molecular Docking with Deep Learning

2021 ◽  
Author(s):  
Andrew McNutt ◽  
Paul Francoeur ◽  
Rishal Aggarwal ◽  
Tomohide Masuda ◽  
Rocco Meli ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Root Mean Square ◽  
Root Mean Square Deviation ◽  
Computational Cost ◽  
Scoring Function ◽  
Binding Pocket ◽  
Protein Docking ◽  
Mean Square ◽  
Mean Square Deviation ◽  
Autodock Vina

Molecular docking computationally predicts the conformation of a small molecule when binding to a receptor. Scoring functions are a vital piece of any molecular docking pipeline as they determine the fitness of sampled poses. Here we describe and evaluate the 1.0 release of the Gnina docking software, which utilizes an ensemble of convolutional neural networks (CNNs) as a scoring function. We also explore an array of parameter values for Gnina 1.0 to optimize docking performance and computational cost. Docking performance, as evaluated by the percentage of targets where the top pose is better than 2A root mean square deviation (Top1), is compared to AutoDock Vina scoring when utilizing explicitly defined binding pockets or whole protein docking. Gnina, utilizing a CNN scoring function to rescore the output poses, outperforms AutoDock Vina scoring on redocking and cross-docking tasks when the binding pocket is defined (Top1 increases from 58% to 73% and from 27% to 37%, respectively) and when the whole protein defines the binding pocket (Top1 increases from 31% to 38% and from 12% to 16%, respectively). The derived ensemble of CNNs generalizes to unseen proteins and ligands and produces scores that correlate well with the root mean square deviation to the known binding pose. We provide the 1.0 version of Gnina under and open source license for use as a molecular docking tool at https://github.com/gnina/gnina.

scholarly journals α-Glucosidase Inhibitory Activity of Cycloartane-Type Triterpenes Isolated from Indonesian Stingless Bee Propolis and Their Structure–Activity Relationship

2019 ◽  
Vol 12 (3) ◽  
pp. 102 ◽  
Author(s):  
Niken Pujirahayu ◽  
Debu Kumar Bhattacharjya ◽  
Toshisada Suzuki ◽  
Takeshi Katayama
Keyword(s):  
Inhibitory Activity ◽  
Antioxidant Activities ◽  
Stingless Bee ◽  
Structure Activity Relationships ◽  
Glucosidase Inhibitor ◽  
Structure Activity ◽  
Glucosidase Inhibitors ◽  
Ic50 Values ◽  
New Type ◽  
Treatment Of Diabetes

This study reports on the antioxidant activity and α-glucosidase inhibitory activity of five cycloartane-type triterpenes isolated from Indonesian stingless bee (Tetragonula sapiens Cockerell) propolis and their structure–activity relationships. The structure of the triterpenes was determined to include mangiferolic acid (1), Cycloartenol (2), ambonic acid (3), mangiferonic acid (4), and ambolic acid (5). The inhibitory test results of all isolated triterpenes against α-glucosidase showed a high potential for inhibitory activity with an IC50 range between 2.46 and 10.72 µM. Among the compounds tested, mangiferonic acid (4) was the strongest α-glucosidase inhibitor with IC50 2.46 µM compared to the standard (–)-epicatechin (1991.1 µM), and also had antioxidant activities with IC50 values of 37.74 ± 6.55 µM. The study on the structure–activity relationships among the compounds showed that the ketone group at C-3 and the double bonds at C-24 and C-25 are needed to increase the α-glucosidase inhibitory activity. The carboxylic group at C-26 is also more important for increasing the inhibitory activity compared with the methyl group. This study provides an approach to help consider the structural requirements of cycloartane-type triterpenes from propolis as α-glucosidase inhibitors. An understanding of these requirements is deemed necessary to find a new type of α-glucosidase inhibitor from the cycloartane-type triterpenes or to improve those inhibitors that are known to help in the treatment of diabetes.

PREPARATION AND CHARACTERISTIC OF BIOLOGICALLY BASED CO-NI-P MICROSTRUCTURE METAL PARTICLES

2010 ◽  
Vol 24 (15n16) ◽  
pp. 3089-3094
Author(s):  
SONGMEI LI ◽  
XIAOLIANG ZHANG ◽  
JIANHUA LIU
Keyword(s):  
Ternary Alloy ◽  
Electroless Deposition ◽  
Metal Particles ◽  
Energy Dispersive Analysis ◽  
X Ray Diffraction ◽  
Microbiological Method ◽  
X Ray ◽  
New Type ◽  
Alloy Microstructure ◽  
Synthetic Methodologies

Biological materials naturally display an astonishing variety of sophisticated nanostructures that are difficult to obtain even with the most technological advanced synthetic methodologies. We describe a new type of Co - Ni - P ternary alloy microstructure particles prepared by electroless deposition based on biological templating. The plating parameters were explored and the microstructure material was studied by microbiological method, scanning election microscope (SEM), energy dispersive analysis (EDS), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). The results showed that the Bacillus were coated by Co - Ni - P ternary alloy successfully and the average contents of Co , Ni , and P in Co - Ni - P coating were about 18.73 wt%, 74.43 wt% and 3.04 wt%, respectively. The structures of as-plated Co - Ni - P alloy were amorphous and exhibited excellent magnetic property. The values of saturation magnetization (Ms), remnants magnetization (Mr) and coercivity (Hc) of the sample were about 18 emu/g, 3.5 emu/g, and 107 Oe, receptivity.

scholarly journals Multienzymatic Processes Involving Baeyer–Villiger Monooxygenases

Catalysts ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 605
Author(s):  
Gonzalo de Gonzalo ◽  
Andrés R. Alcántara
Keyword(s):  
Direct Conversion ◽  
Cascade Reactions ◽  
Oxidative Enzymes ◽  
Redox Enzymes ◽  
Cyclic Ketones ◽  
Subsequent Reaction ◽  
Parallel Methods ◽  
Whole Cells ◽  
Synthetic Methodologies ◽  
Conversion Of Alcohols

Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzing the insertion of an oxygen atom between a carbonylic Csp2 and the Csp3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones. These enzymes are dependent on nicotinamides (NAD(P)H) for the flavin reduction and subsequent reaction with molecular oxygen. BVMOs can be included in cascade reactions, coupled to other redox enzymes, such as alcohol dehydrogenases (ADHs) or ene-reductases (EREDs), so that the direct conversion of alcohols or α,β-unsaturated carbonylic compounds to the corresponding esters can be achieved. In the present review, the different synthetic methodologies that have been performed by employing multienzymatic strategies with BVMOs combining whole cells or isolated enzymes, through sequential or parallel methods, are described, with the aim of highlighting the advantages of performing multienzymatic systems, and show the recent advances for overcoming the drawbacks of using BVMOs in these techniques.

scholarly journals In vitro evaluation of the anti-diabetic potential of Helichrysum petiolare Hilliard & B.L. Burtt using HepG2 (C3A) and L6 cell lines

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1240
Author(s):  
Adebowale Emmanuel Aladejana ◽  
Graeme Bradley ◽  
Anthony Jide Afolayan
Keyword(s):  
Glucose Uptake ◽  
Cell Lines ◽  
Ethanol Extract ◽  
Eastern Cape ◽  
Treatment Of Diabetes ◽  
Pharmacologically Active ◽  
Lipase Inhibition ◽  
L6 Myocytes

Background: Helichrysum petiolare Hilliard & B.L. Burtt has been listed in a survey of plants used in traditional medicine for the treatment of type 2 diabetes in the Eastern Cape of South Africa. In this study, the antidiabetic potentials of ethanol, cold aqueous (CAQ) and boiled aqueous (BAQ) extracts of H. petiolare were investigated. Methods: The cytotoxic and glucose utilization effects of the extracts were evaluated using L6 myocytes and HepG2 (C3A) hepatocytes. α-amylase, α-glucosidase and lipase inhibition assays were also carried out. Results: The ethanol extract showed significant cytotoxic effects in the treated cells. Both BAQ and CAQ extracts significantly increased glucose uptake in L6 and C3A cell lines. The CAQ extract enhanced glucose uptake more in the L6 myocytes than in the C3A cell-lines hepatocytes. The BAQ extract showed higher levels of inhibition on α–amylase and α-glucosidase than CAQ. The activities were not significantly different from acarbose. However, BAQ showed lower lipase inhibition than acarbose (p<0.05). Conclusions: The BAQ and CAQ extracts of H. petiolare may, therefore, contain pharmacologically active and relatively non-toxic hypoglycaemic chemicals, which may be effective substitutes in the treatment of diabetes mellitus.

scholarly journals Synthesis, applications and Structure-Activity Relationship (SAR) of cinnamic acid derivatives: a review

2021 ◽  
Vol 10 (1) ◽  
pp. e28010111691
Author(s):  
Saraliny Bezerra França ◽  
Paulo Ricardo dos Santos Correia ◽  
Ilton Barros Daltro de Castro ◽  
Edeildo Ferreira da Silva Júnior ◽  
Maria Ester de Sá Barreto Barros ◽  
...  
Keyword(s):  
Cinnamic Acid ◽  
Therapeutic Potential ◽  
Structure Activity Relationship ◽  
Bioactive Molecules ◽  
Activity Relationship ◽  
Cinnamic Acid Derivatives ◽  
Structure Activity ◽  
Synthetic Routes ◽  
Synthetic Methodologies ◽  
Pharmacologically Active

The article aims to analyze the progress of the evolution of cinnamic acid derivatives through a bibliographic review, describing the main synthetic routes in obtaining this class, as well as remarkable biological applications and application of the structure-activity relationship (SAR) as a strategy for design pharmacologically active molecules. The methodology used consists of reading and analyzing articles, whose approach is descriptive, with data being collected regarding the therapeutic potential of derivatives of cinnamic acid and its relationship with structural scaffolding, as well as the most widely used synthetic approaches. As a result, it was observed that cinnamic acid and its derivatives from natural sources can be synthesized in appreciable quantities with varied synthetic routes, as well as being candidates for therapeutic agents, since they have several therapeutic applications against diabetes, infectious and degenerative diseases, among others, in addition to presenting activity such as pest control, which has attracted the attention of academic and industrial researchers. These compounds are highly versatile since their activity is intrinsically associated with the mode of interaction between the structure and its molecular target. However, in nature they are obtained in small quantities, therefore, the development of new approaches of synthetic methodologies to obtain such compounds in substantial quantities and linked to medicinal chemistry can contribute to the development of very effective bioactive molecules in comparison with their precursors.

scholarly journals In vitro evaluation of the anti-diabetic potential of Helichrysum petiolare Hilliard & B.L. Burtt using HepG2 (C3A) and L6 cell lines

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 1240
Author(s):  
Adebowale Emmanuel Aladejana ◽  
Graeme Bradley ◽  
Anthony Jide Afolayan
Keyword(s):  
Glucose Uptake ◽  
Cell Lines ◽  
Ethanol Extract ◽  
Eastern Cape ◽  
Treatment Of Diabetes ◽  
Pharmacologically Active ◽  
Lipase Inhibition ◽  
L6 Myocytes

Background: Helichrysum petiolare Hilliard & B.L. Burtt has been listed in a survey of plants used in traditional medicine for the treatment of type 2 diabetes in the Eastern Cape of South Africa. In this study, the antidiabetic potentials of ethanol, cold aqueous (CAQ) and boiled aqueous (BAQ) extracts of H. petiolare were investigated. Methods: The cytotoxic and glucose utilization effects of the extracts were evaluated using L6 myocytes and HepG2 (C3A) hepatocytes. α-amylase, α-glucosidase and lipase inhibition assays were also carried out. Results: The ethanol extract showed significant cytotoxic effects in the treated cells. Both BAQ and CAQ extracts significantly increased glucose uptake in L6 and C3A cell lines. The CAQ extract enhanced glucose uptake more in the L6 myocytes than in the C3A cell-lines hepatocytes. The BAQ extract showed higher levels of inhibition on α–amylase and α-glucosidase than CAQ. The activities were not significantly different from acarbose. However, BAQ showed lower lipase inhibition than acarbose (p<0.05). Conclusions: The BAQ and CAQ extracts of H. petiolare may, therefore, contain pharmacologically active and relatively non-toxic hypoglycaemic chemicals, which may be effective substitutes in the treatment of diabetes mellitus.

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