Elucidation of Phosphodiesterase-1 Inhibitory Effect of Some Selected Natural Polyphenolics Using In Vitro and In Silico Methods

The investigation aimed to study the in vitro and in silico antioxidant properties of Melissa officinalis subsp. officinalis essential oil (MOEO). The chemical composition of MOEO was determined using GC–MS analysis. Among 36 compounds identified in MOEO, the main were beta-cubebene (27.66%), beta-caryophyllene (27.41%), alpha-cadinene (4.72%), caryophyllene oxide (4.09%), and alpha-cadinol (4.07%), respectively. In vitro antioxidant properties of MOEO have been studied in 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging, and inhibition of β-carotene bleaching assays. The half-maximal inhibitory concentration (IC50) for the radical scavenging abilities of ABTS and DPPH were 1.225 ± 0.011 μg/mL and 14.015 ± 0.027 μg/mL, respectively, demonstrating good antioxidant activity. Moreover, MOEO exhibited a strong inhibitory effect (94.031 ± 0.082%) in the β-carotene bleaching assay by neutralizing hydroperoxides, responsible for the oxidation of highly unsaturated β-carotene. Furthermore, molecular docking showed that the MOEO components could exert an in vitro antioxidant activity through xanthine oxidoreductase inhibition. The most active structures are minor MOEO components (approximately 6%), among which the highest affinity for the target protein belongs to carvacrol.

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Predicting Absorption-Distribution Properties of Neuroprotective Phosphine-Borane Compounds Using In Silico Modeling and Machine Learning

Molecules ◽

10.3390/molecules26092505 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2505

Author(s):

Raheem Remtulla ◽

Sanjoy Kumar Das ◽

Leonard A. Levin

Keyword(s):

Machine Learning ◽

Neural Networks ◽

In Silico ◽

Disulfide Bonds ◽

Oral Absorption ◽

In Vivo Studies ◽

Drug Candidates ◽

In Silico Methods

Phosphine-borane complexes are novel chemical entities with preclinical efficacy in neuronal and ophthalmic disease models. In vitro and in vivo studies showed that the metabolites of these compounds are capable of cleaving disulfide bonds implicated in the downstream effects of axonal injury. A difficulty in using standard in silico methods for studying these drugs is that most computational tools are not designed for borane-containing compounds. Using in silico and machine learning methodologies, the absorption-distribution properties of these unique compounds were assessed. Features examined with in silico methods included cellular permeability, octanol-water partition coefficient, blood-brain barrier permeability, oral absorption and serum protein binding. The resultant neural networks demonstrated an appropriate level of accuracy and were comparable to existing in silico methodologies. Specifically, they were able to reliably predict pharmacokinetic features of known boron-containing compounds. These methods predicted that phosphine-borane compounds and their metabolites meet the necessary pharmacokinetic features for orally active drug candidates. This study showed that the combination of standard in silico predictive and machine learning models with neural networks is effective in predicting pharmacokinetic features of novel boron-containing compounds as neuroprotective drugs.

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Glucocorticoid resistance conferring mutation in the C-terminus of GR alters the receptor conformational dynamics

Scientific Reports ◽

10.1038/s41598-021-92039-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anna Kaziales ◽

Florian Rührnößl ◽

Klaus Richter

Keyword(s):

Glucocorticoid Receptor ◽

Steroid Hormones ◽

In Silico ◽

Conformational Dynamics ◽

Glucocorticoid Resistance ◽

Physiological Processes ◽

C Terminus ◽

Hsp90 Chaperone ◽

In Silico Methods

AbstractThe glucocorticoid receptor is a key regulator of essential physiological processes, which under the control of the Hsp90 chaperone machinery, binds to steroid hormones and steroid-like molecules and in a rather complicated and elusive response, regulates a set of glucocorticoid responsive genes. We here examine a human glucocorticoid receptor variant, harboring a point mutation in the last C-terminal residues, L773P, that was associated to Primary Generalized Glucocorticoid Resistance, a condition originating from decreased affinity to hormone, impairing one or multiple aspects of GR action. Using in vitro and in silico methods, we assign the conformational consequences of this mutation to particular GR elements and report on the altered receptor properties regarding its binding to dexamethasone, a NCOA-2 coactivator-derived peptide, DNA, and importantly, its interaction with the chaperone machinery of Hsp90.

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In Silico Docking and In Vitro Approaches towards BACE1 and Cholinesterases Inhibitory Effect of Citrus Flavanones

Molecules ◽

10.3390/molecules23071509 ◽

2018 ◽

Vol 23 (7) ◽

pp. 1509 ◽

Cited By ~ 11

Author(s):

Seungeun Lee ◽

Kumju Youn ◽

GyuTae Lim ◽

Jinhyuk Lee ◽

Mira Jun

Keyword(s):

In Silico ◽

Inhibitory Effect ◽

In Silico Docking

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Silver nanoparticle uptake in the human lung assessed through in-vitro and in-silico methods

Environmental Pollution ◽

10.1016/j.envpol.2019.113880 ◽

2020 ◽

Vol 259 ◽

pp. 113880 ◽

Cited By ~ 2

Author(s):

Kathryn Jalink ◽

Sammi Sham Yin Cheng ◽

S. Ben Ireland ◽

M.A.F. Louise Meunier

Keyword(s):

Silver Nanoparticle ◽

In Silico ◽

Human Lung ◽

Nanoparticle Uptake ◽

In Silico Methods

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In Vitro, In Vivo, and In Silico Methods for Assessment of Muscle Size and Muscle Growth Regulation

Shock ◽

10.1097/shk.0000000000001498 ◽

2020 ◽

Vol 53 (5) ◽

pp. 605-615

Author(s):

Joseph E. Rupert ◽

Daenique H. A. Jengelley ◽

Teresa A. Zimmers

Keyword(s):

In Silico ◽

Growth Regulation ◽

Muscle Growth ◽

Muscle Size ◽

In Silico Methods

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In Vitro and In Silico Evaluation for the Inhibitory Action of O. basilicum Methanol Extract on α-Glucosidase and α-Amylase

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5515775 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Siba Shanak ◽

Najlaa Bassalat ◽

Raghad Albzoor ◽

Sleman Kadan ◽

Hilal Zaid

Keyword(s):

Caffeic Acid ◽

In Silico ◽

Type Ii Diabetes ◽

Methanol Extract ◽

Inhibitory Effect ◽

Major Health ◽

In Silico Docking ◽

Aerial Parts ◽

Health Complications

Diabetes mellitus is a metabolic disease that predominates, nowadays. It causes hyperglycemia and consequently major health complications. Type II diabetes is the most common form and is a result of insulin resistance in the target tissues. To treat this disease, several mechanisms have been proposed. The most direct route is via inhibiting the intestinal enzymes, e.g., α-glucosidase and α-amylase, responsible for intestinal polysaccharide digestion that therefore would reduce the absorption of monosugars through the intestinal walls. In this study, we shed the light on this route by testing the inhibitory effect of Ocimum basilicum extract on the enzymes α-glucosidase and α-amylase in vitro and in silico. Experimental procedures were performed to test the effect of the O. basilicum methanol extract from aerial parts followed by the in silico docking. 500 μg/mL of the extract led to 70.2% ± 8.6 and 25.4% ± 3.3 inhibition on α-glucosidase and α-amylase activity, respectively. Similarly, the effect of caffeic acid, a major extract ingredient, was also tested, and it caused 42.7% ± 3.0 and 47.1% ± 4.0 inhibition for α-amylase and α-glucosidase, respectively. Docking experiments were performed to predict the phytochemicals responsible for this robust inhibitory activity in the O. basilicum extracts. Several compounds have shown variable levels of inhibition, e.g., caffeic acid, pyroglutamic acid, and uvasol. The results indicated that O. basilicum can be a potent antidiabetic drug.

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Evaluation of antileishmanial potential of Gentiana kurroo Royle by in vitro and in silico methods

Journal of Applied Pharmaceutical Science ◽

10.7324/japs.2018.8222 ◽

2018 ◽

Keyword(s):

In Silico ◽

Gentiana Kurroo ◽

In Silico Methods

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Cocoa (Theobroma cacao L.) Seed Proteins’ Anti-Obesity Potential through Lipase Inhibition Using In Silico, In Vitro and In Vivo Models

Foods ◽

10.3390/foods9101359 ◽

2020 ◽

Vol 9 (10) ◽

pp. 1359

Author(s):

Luis Jorge Coronado-Cáceres ◽

Griselda Rabadán-Chávez ◽

Luis Mojica ◽

Blanca Hernández-Ledesma ◽

Lucía Quevedo-Corona ◽

...

Keyword(s):

In Silico ◽

Seed Proteins ◽

Inhibitory Effect ◽

Mean Value ◽

Intragastric Administration ◽

Degree Of Hydrolysis ◽

In Vivo Models ◽

Hydrolysis Of

The aim of this study was to determine the pancreatic lipase (PL) inhibitory effect of cocoa protein (CP) hydrolysates (CPH) using in silico and in vitro approaches, and an in vivo high-fat diet (HF) obese rat model. The results showed better theoretical affinity on PL for cocoa peptides EEQR, GGER, QTGVQ, and VSTDVNIE released from vicilin and albumins (−6.5, −6.3, −6.2, and −6.1 kcal/mol, respectively). Absorption, distribution, metabolism, and excretion (ADMET) prediction showed the human intestinal absorption (HIA) capacity of orlistat and eight cocoa peptides, demonstrating that they presented a low probability of toxicity with values lower than 0.6, while the orlistat has a high probability of hepatotoxicity with a mean value of 0.9. CPH (degree of hydrolysis of 55%) inhibited PL with an IC50 (concentration needed to inhibit 50% of enzyme activity) value of 1.38 mg/mL. The intragastric administration of 150 mg CP/kg/day to rats increased total lipids and triglycerides excretion in feces, ranging from 11% to 15% compared to the HF-diet. The HF + CP-diet also significantly decreased (p < 0.05) the apparent rate of fat absorption compared with the HF group. These results suggest that CP has anti-obesity potential by inhibiting PL, thus helping to prevent the development of non-communicable diseases.

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Bioassays and In Silico Methods in the Identification of Human DNA Topoisomerase IIα Inhibitors

Current Medicinal Chemistry ◽

10.2174/0929867325666180306165725 ◽

2018 ◽

Vol 25 (28) ◽

pp. 3286-3318 ◽

Cited By ~ 7

Author(s):

Kaja Bergant ◽

Matej Janezic ◽

Andrej Perdih

Keyword(s):

In Silico ◽

In Vivo Studies ◽

Topoisomerase Iiα ◽

Dna Topoisomerase ◽

Human Dna ◽

Practical Guidelines ◽

In Silico Methods ◽

Dna Topoisomerase Iiα

Background: The family of DNA topoisomerases comprises a group of enzymes that catalyse the induction of topological changes to DNA. These enzymes play a role in the cell replication machinery and are, therefore, important targets for anticancer drugs - with human DNA topoisomerase IIα being one of the most prominent. Active compounds targeting this enzyme are classified into two groups with diverse mechanisms of action: DNA poisons act by stabilizing a covalent cleavage complex between DNA and the topoisomerase enzyme, transforming it into a cellular toxin, while the second diverse group of catalytic inhibitors, provides novel inhibition avenues for tackling this enzyme due to frequent occurrence of side effects observed during the DNA poison therapy. Methods: Based on a comprehensive literature search we present an overview of available bioassays and in silico methods in the identification of human DNA topoisomerase IIα inhibitors. Results and Conclusion: A comprehensive outline of the available methods and approaches that explore in detail the in vitro mechanistic and functional aspects of the topoisomerase IIα inhibition of both topo IIα inhibitor groups is presented. The utilized in vitro cell-based assays and in vivo studies to further explore the validated topo IIα inhibitors in subsequent preclinical stages of the drug discovery are discussed. The potential of in silico methods in topoisomerase IIα inhibitor discovery is outlined. A list of practical guidelines was compiled to aid new as well experienced researchers in how to optimally approach the design of targeted inhibitors and validation in the preclinical drug development stages.

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