Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling

Elhady, Sameh S.; Alshobaki, Noha M.; Elfaky, Mahmoud A.; Koshak, Abdulrahman E.; Alharbi, Majed; Abdelhameed, Reda F. A.; Darwish, Khaled M.

doi:10.3390/metabo13080942

Cited by 3 publications

(1 citation statement)

References 100 publications

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“…We explore RMSD of individual ligands, outstanding stability was observed within the target protein binding sites for the simulated ligands at different time frames (C-0, C-50, C-120, C-150, and C-200), as shown in Figure 9 , with variations of different Å values and results where compared and followed by Elhady et al (2023) . These simulations showed minimal fluctuations and nearly constant trajectories compared to other ligands.…”

Section: Resultsmentioning

confidence: 99%

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

Zafar,

Safder,

Imran Afridi

et al. 2023

Front. Chem.

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Introduction: Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments.Material and Methods: For in vitro study we used thin layer chromatography (TAC) for phytochemical screening, total antioxidant capacity (TLC) assay for antioxidant capacity, and hemolytic activity test for toxicity of Neuropilins (NRPs). We performed bioinformatic analyses to predict protein structures, molecular docking, pharmacophore modeling, and virtual screening to reveal interactions with oncogenes. We conducted 200 ns Molecular Dynamics (MD) simulations and MMGBSA calculations to assess the complex dynamics and stability.Results: We identified phytochemical constituents in Nigella sativa leaves, including tannins, saponins, steroids, and cardiac glycosides, while phlobatannins and terpenoids were absent. The leaves contained 9.4% ± 0.04% alkaloids and 1.9% ± 0.05% saponins. Methanol extract exhibited the highest yield and antioxidant capacity, with Total Flavonoid Content at 127.51 ± 0.76 mg/100 g and Total Phenolic Content at 134.39 ± 0.589 mg GAE/100 g. Hemolysis testing showed varying degrees of hemolysis for different extracts. In-silico analysis indicated stable Neuropilin complexes with key signaling pathways relevant for anti-cancer therapy. Molecular docking scores at different possesses (0, C-50, C −80, C-120,C −150, C −200 ns) revealed strong hydrogen bonding in the complexes and showed −12.9, −11.6, and −11.2 binding Affinities (kcal/mol) to support their stability. Our MD simulations analysis at 200ns confirmed the stability of Neuropilin complexes with the signaling pathways protein PI3K. The calculated binding free energies using MMGBSA provided valuable quantitative information on ligand potency on different time steps. These findings highlight the potential health benefits of N. sativa leaves and their possible role in anti-cancer treatments targeting angiogenesis.Conclusion:Nigella sativa leaves have shown significant medical potential due to their bioactive compounds, which exhibit strong properties in supporting organogenic processes related to cancer. Furthermore, studies have highlighted the promising role of neuropilins in anticancer treatment, demonstrating stable interactions and potential as targeted therapy specifically for breast cancer.

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Section: Resultsmentioning

confidence: 99%

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

Zafar,

Safder,

Imran Afridi

et al. 2023

Front. Chem.

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Synthesis of Pyrazolo[3,4‐b]pyridine Derivatives and Their In‐Vitro and In‐Silico Antidiabetic Activities

Rafique,

Maqbool,

Javed

2024

J of Cellular Biochemistry

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In the current study, new pyrazolo[3,4‐b]pyridine esters, hydrazides, and Schiff bases have been synthesized starting from 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐amine. The first step involved solvent‐free synthesis of pyrazolo[3,4‐b]pyridine‐6‐carboxylate derivatives (2a–d) with 55%–70% yield in the minimum time frame compared with the conventional refluxing method, which was followed by the synthesis of corresponding hydrazides (3a–d) and hydrazones (4a–e). The structures of the synthesized derivatives were confirmed using element analysis, FT‐IR, 1H NMR, 13C NMR, and LC‐MS techniques. Synthesized hydrazides (3a–d) and hydrazones (4a–e) were also tested for their in‐vitro antidiabetic activity and found that all the compounds exhibited significant antidiabetic activity, while 3c (IC50 = 9.6 ± 0.5 μM) among the hydrazides and 4c (IC50 = 13.9 ± 0.7 μM) among the hydrazones were found to be more active in comparison to other synthesized derivatives. These in‐vitro results were further validated via docking studies against the α‐amylase enzyme using the reference drug acarbose (200.1 ± 10.0 μM). The results were greatly in agreement with their in‐vitro studies and these derivatives can be encouraging candidates for further in‐vivo studies in mice models.

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Anti-Diabetic Activities and Molecular Docking Studies of Aryl-Substituted Pyrazolo[3,4-b]pyridine Derivatives Synthesized via Suzuki Cross-Coupling Reaction

Rafique,

Maqbool,

Rutjes

et al. 2024

Pharmaceuticals

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Pyrazolo[3,4-b]pyridine scaffolds have been heavily exploited in the development of nitrogen-containing heterocycles with numerous therapeutic applications in the field of medicinal and pharmaceutical chemistry. The present work describes the synthesis of eighteen biaryl pyrazolo[3,4-b]pyridine ester (6a–i) and hydrazide (7a–i) derivatives via the Suzuki cross-coupling reaction. These derivatives were subsequently screened for their therapeutic potential to inhibit the diabetic α-amylase enzyme, which is a key facet of the development of anti-diabetic agents. Initially, the ethyl 4-(4-bromophenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-6-carboxylate 4 was synthesized through a modified Doebner method under solvent-free conditions, providing an intermediate for further derivatization with a 60% yield. This intermediate 4 was subjected to Suzuki cross-coupling, reacting with electronically diverse aryl boronic acids to obtain the corresponding pyrazolo[3,4-b]pyridine ester derivatives (6a–i). Following this, the biaryl ester derivatives (6a–i) were converted into hydrazide derivatives (7a–i) through a straightforward reaction with hydrazine monohydrate and were characterized using 1H-NMR, 13C-NMR, and LC-MS spectroscopic techniques. These derivatives were screened for their α-amylase inhibitory chemotherapeutic efficacy, and most of the biaryl ester and hydrazide derivatives demonstrated promising amylase inhibition. In the (6a–i) series, the compounds 6b, 6c, 6h, and 6g exhibited excellent inhibition, with almost similar IC50 values of 5.14, 5.15, 5.56, and 5.20 μM, respectively. Similarly, in the series (7a–i), the derivatives 7a, 7b, 7c, 7d, 7f, 7g, and 7h displayed excellent anti-diabetic activities of 5.21, 5.18, 5.17, 5.12, 5.10, 5.16, and 5.19 μM, respectively. These in vitro results were compared with the reference drug acarbose (IC50 = 200.1 ± 0.15 μM), demonstrating better anti-diabetic inhibitory activity in comparison to the reference drug. The in silico molecular docking study results were consistent with the experimental biological findings, thereby supporting the in vitro pharmaceutical efficacy of the synthesized derivatives.

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Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling

Cited by 3 publications

References 100 publications

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

Synthesis of Pyrazolo[3,4‐b]pyridine Derivatives and Their In‐Vitro and In‐Silico Antidiabetic Activities

Anti-Diabetic Activities and Molecular Docking Studies of Aryl-Substituted Pyrazolo[3,4-b]pyridine Derivatives Synthesized via Suzuki Cross-Coupling Reaction

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