QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties

fadili, Mohamed El; Er-rajy, Mohammed; Imtara, Hamada; Noman, Omar M.; Mothana, Ramzi A.; Abdullah, Sheaf; Zerougui, Sara; Elhallaoui, Menana

doi:10.1016/j.heliyon.2023.e13706

Cited by 17 publications

(5 citation statements)

References 50 publications

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“…Molecular docking was performed via the following steps: (1) Three-dimensional structures of targeted proteins were extracted from the Research Collaboratory for Structural Bioinformatics (RCSB) PDB basis ( https://www.rcsb.org/ ); (2) Proteins in PDB files were prepared using Discovery Studio 2021 software ( https://www.3ds.com/products-services/biovia/products/molecular-modeling-simulation/biovia-discovery-studio/ ) 24 , 25 , removing all co-crystallized ligands and water molecules, and adding the charges of Gasteiger; (3) The examined ligands (C7, C8, and C12) and the prepared proteins were converted from PDB to PDBQT files using Autodock software version 4.2 (10.1186/1758-2946-3-12) 26 ; (4) Grid boxes were centralized on each targeted protein, maximizing dimensions in three directions (OX, OY, and OZ) with a spacing of 0.375 Å, as shown in Table 1 . The produced complexes were visualized using Discovery Studi 2021 software 27 .…”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of different solvent extracts of Ferula communis L. fruit reveals phenolic compounds and their biological properties via in vitro and in silico assays

Nouioura,

El fadili,

El Barnossi

et al. 2024

Sci Rep

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Although giant fennel is recognized as a “superfood” rich in phytochemicals with antioxidant activity, research into the antibacterial properties of its fruits has been relatively limited, compared to studies involving the root and aerial parts of the plant. In this study, seven solvents—acetone, methanol, ethanol, ethyl acetate, chloroform, water, and hexane—were used to extract the chemical constituents of the fruit of giant fennel (Ferula communis), a species of flowering plant in the carrot family Apiaceae. Specific attributes of these extracts were investigated using in silico simulations and in vitro bioassays. High-performance liquid chromatography equipped with a diode-array detector (HPLC–DAD) identified 15 compounds in giant fennel extract, with p-coumaric acid, 3-hydroxybenzoic acid, sinapic acid, and syringic acid being dominant. Among the solvents tested, ethanol demonstrated superior antioxidant activity and phenolic and flavonoid contents. F. communis extracts showed advanced inhibition of gram-negative pathogens (Escherichia coli and Proteus mirabilis) and variable antifungal activity against tested strains. Molecular docking simulations assessed the antioxidative, antibacterial, and antifungal properties of F. communis, facilitating innovative therapeutic development through predicted compound–protein interactions. In conclusion, the results validate the ethnomedicinal use and potential of F. communis. This highlights its significance in natural product research and ethnopharmacology.

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Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of different solvent extracts of Ferula communis L. fruit reveals phenolic compounds and their biological properties via in vitro and in silico assays

Nouioura,

El fadili,

El Barnossi

et al. 2024

Sci Rep

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“…Thereafter, the major compound’s inhibition mechanism was evaluated using molecular docking technology toward antioxidant, antifungal, and antibacterial proteins. The physicochemical and pharmacokinetic features of ADMET were predicted using SWISADME and PKCSM online servers. , Chlorogenic acid, as the major compound, as extracted with the highest value of area (AUC of 43.68%), was docked to the NADPH oxidase from Lactobacillus, the secreted aspartic protease from Candida albicans, and the crystal structure of the FimH lectin domain from Escherichia coli K12 , encoded in protein data bank (PDB) by 2CDU, 1ZAP, and 4XO8, respectively. Three-dimensional crystal structures of oxidoreductase, aspartic protease, and cell adhesion proteins were uploaded from the RCSB PDB, with resolutions of 1.8, 2.50, and 1.7 Å, respectively.…”

Section: Methodsmentioning

confidence: 99%

Phytochemical, Antioxidant Activity, and Toxicity of Wild Medicinal Plant of Melitotus albus Extracts, In Vitro and In Silico Approaches

Ed-Dahmani,

El fadili,

Kandsi

et al. 2024

ACS Omega

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Morocco is known for its high plant biodiversity, but many plants are poorly valorized. For this reason, this study aims to valorize the methanolic and aqueous extracts of Melitotus albus leaves by studying their antioxidant activity and toxicity. The extracts’ antioxidant activity is assessed using the FRAP, DPPH, CAT, and ABTS methods. The chemical composition was determined using LC–MS analysis and evaluated using in silico studies. The results revealed that the total polyphenol content of the aqueous extract, 259.26 ± 7.79 (mg GAE/g), is higher than that of the methanolic extract, 131.41 ± 12.64 (mg GAE/g). The antioxidant activity by the methods of DPPH, ABTS, and phosphor molybdenum of aqueous extracts (0.087 ± 0.015, 0.014 ± 0.001 and 6.157 ± 1.050 mg eq vit C/g, respectively) is greater than that of methanolic extracts (0.107 ± 0.02, 0.167 ± 0.03, and 0.453 ± 0.014 mg eq vit C/g, respectively). The reducing power of iron (FRAP) shows that the methanolic extract has a greater reducing power than that of the aqueous extract with a low IC50 (0.011 ± 0.003 and 0.199 ± 0.016 mg/mL, respectively). The study of acute and subacute toxicity shows that the administration of the aqueous extract of M. albus at different doses increases the body weight of rats without modifying their general behavior. The M. albus extract had a 99.99% total phenolic content, as determined by LC–MS, consisting of 12 different components. The primary constituents of the extract are chlorogenic acid (43.68%), catechin/epicatechin (24.82%), quercetin-3-O-glucuronic acid (9.91%), naringin (7.64%), and p-hydroxybenzoic/salicylic acid (2.95%). The in-silico study showed that these compounds can passively permeate through the blood and have a beneficial effect on various organs of the body. Based on these results, M. albus can be used as a medicinal plant in phytotherapy, cosmetics, or as a dietary supplement. The bioactive compounds of these plants will require a lot of further effort in terms of isolation and characterization.

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“…Prior to docking, the protein structures were cleaned by removing water molecules, ligands, and cofactors. The Gasteiger charges were then computed, and polar hydrogens were inserted, while non-polar hydrogens were combined using Autodock [ 52 , 53 ]. The Auto Grid technique was used to construct a 3D grid that would analyze the energy of complex ligand–protein interactions.…”

Section: Methodsmentioning

confidence: 99%

“…The central grid box in the protein was found at (2.124, 9.760, and 46.315) by the ligand location in the protein. The molecular docking studies were performed using the Lamarckian Genetic Algorithm (LGA), which is known for being one of the best docking methods available in Autodock [ 52 , 53 , 54 ]. To visualize binding modes, the type of interactions, and exhibit the surfaces of cavities, Biovia Discovery Studio software 2021 was used [ 55 ].…”

Section: Methodsmentioning

confidence: 99%

“…The HOMO and LUMO energies are used for the determination of global reactivity descriptors such as chemical potential (μ), hardness (η), softness (δ), and electrophilicity (ω). These parameters are calculated by the following equations [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]:

…”

Section: Methodsmentioning

confidence: 99%

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Computer-Aided Strategy on 5-(Substituted benzylidene) Thiazolidine-2,4-Diones to Develop New and Potent PTP1B Inhibitors: QSAR Modeling, Molecular Docking, Molecular Dynamics, PASS Predictions, and DFT Investigations

Derki,

Kerassa,

Belaidi

et al. 2024

Molecules

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A set of 5-(substituted benzylidene) thiazolidine-2,4-dione derivatives was explored to study the main structural requirement for the design of protein tyrosine phosphatase 1B (PTP1B) inhibitors. Utilizing multiple linear regression (MLR) analysis, we constructed a robust quantitative structure–activity relationship (QSAR) model to predict inhibitory activity, resulting in a noteworthy correlation coefficient (R2) of 0.942. Rigorous cross-validation using the leave-one-out (LOO) technique and statistical parameter calculations affirmed the model’s reliability, with the QSAR analysis revealing 10 distinct structural patterns influencing PTP1B inhibitory activity. Compound 7e(ref) emerged as the optimal scaffold for drug design. Seven new PTP1B inhibitors were designed based on the QSAR model, followed by molecular docking studies to predict interactions and identify structural features. Pharmacokinetics properties were assessed through drug-likeness and ADMET studies. After that density functional theory (DFT) was conducted to assess the stability and reactivity of potential diabetes mellitus drug candidates. The subsequent dynamic simulation phase provided additional insights into stability and interactions dynamics of the top-ranked compound 11c. This comprehensive approach enhances our understanding of potential drug candidates for treating diabetes mellitus.

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QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties

Cited by 17 publications

References 50 publications

Comprehensive analysis of different solvent extracts of Ferula communis L. fruit reveals phenolic compounds and their biological properties via in vitro and in silico assays

Comprehensive analysis of different solvent extracts of Ferula communis L. fruit reveals phenolic compounds and their biological properties via in vitro and in silico assays

Phytochemical, Antioxidant Activity, and Toxicity of Wild Medicinal Plant of Melitotus albus Extracts, In Vitro and In Silico Approaches

Computer-Aided Strategy on 5-(Substituted benzylidene) Thiazolidine-2,4-Diones to Develop New and Potent PTP1B Inhibitors: QSAR Modeling, Molecular Docking, Molecular Dynamics, PASS Predictions, and DFT Investigations

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