Molecular dynamics simulations reveal the inhibitory mechanism of Withanolide A against α-glucosidase and α-amylase

Oyewusi, Habeebat Adekilekun; Wu, Yuan Seng; Safi, Sher Zaman; Wahab, Roswanira Abdul; Hatta, Mohd Hayrie Mohd; Batumalaie, Kalaivani

doi:10.1080/07391102.2022.2104375

Cited by 10 publications

(4 citation statements)

References 68 publications

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“…An in‐silico investigation found that withanolide A was more efficient against α‐amylase and β‐glucosidase than the synthetic Acarbose medication. Pharmacological profiling, molecular docking, and dynamic modeling were used to investigate ligand interactions, binding affinity, and stability (Kumar et al, 2022; Oyewusi et al, 2022). Additionally, utilizing molecular docking studies, the effectiveness of Withaferin A was evaluated against several target proteins connected to hypercholesterolemia, cancer, and Type‐II diabetes, and the most suitable mechanism of action was identified (Surya Ulhas & Malaviya, 2022).…”

Section: Withania Somnifera: Therapeutically Potential Activitiesmentioning

confidence: 99%

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

Yadav,

Tripathi,

Sangwan

2024

Phytotherapy Research

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Withania somnifera, the plant named Indian ginseng, Ashwagandha, or winter cherry, has been used since ancient times to cure various health ailments. Withania somnifera is rich in constituents belonging to chemical classes like alkaloids, saponins, flavonoids, phenolic acids, and withanolides. Several chemotypes were identified based on their phytochemical composition and credited for their multiple bioactivities. Besides, exhibiting neuroprotective, immunomodulatory, adaptogenic, anti‐stress, bone health, plant has shown promising anti‐cancer properties. Several withanolides have been reported to play a crucial role in cancer; they target cancer cells by different mechanisms such as modulating the expression of tumor suppressor genes, apoptosis, telomerase expression, and regulating cell signaling pathway. Though, many treatments are available for cancer; however, to date, no assured reliable cure for cancer is made available. Additionally, synthetic drugs may lead to development of resistance in time; therefore, focus on new and natural drugs for cancer therapeutics may prove a longtime effective alternative. This current report is a comprehensive combined analysis upto 2023 with articles focused on bio‐activities of plant Withania somnifera from various sources, including national and international government sources. This review focuses on understanding of various mechanisms and pathways to inhibit uncontrolled cell growth by W. somnifera bioactives, as reported in literature. This review provides a recent updated status of the W. somnifera on pharmacological properties in general and anti‐cancer in particular and may provide a guiding resource for researchers associated with natural product‐based cancer research and healthcare management.

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Section: Withania Somnifera: Therapeutically Potential Activitiesmentioning

confidence: 99%

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

Yadav,

Tripathi,

Sangwan

2024

Phytotherapy Research

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“…This allowed us to validate the results obtained from the molecular dynamics (MD) investigation. The binding free energy for each AzrBmH2-dye complex was calculated following the methods described in our previous studies (Romes et al, 2021;Oyewusi et al, 2022;2022c). The presented results are the average of triplicated MM-PBSA calculations.…”

Section: Calculation Of Binding Free Energymentioning

confidence: 99%

Bioinformatics analysis and molecular dynamics simulations of azoreductases (AzrBmH2) from Bacillus megaterium H2 for the decolorization of commercial dyes

Oyewusi,

Wahab,

Akinyede

et al. 2023

Preprint

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The present study aimed to investigate the decolorization of various commercial dyes through bioinformatics analysis, utilizing techniques such as molecular docking, molecular dynamics simulation, and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA). These analyses were conducted on different commercial dyes to evaluate their potential for biodegradation. In this study, four commercial dyes, namely acid orange 7, cresol red, methylene blue, and malachite green, were selected as potential targets for degradation by azoreductases (AzrBmH21, AzrBmH22/3, and AzrBmH24/5) derived from Bacillus megaterium H2. The prediction of ligand binding or catalytic sites for AzrBmH21, AzrBmH22/3, and AzrBmH24/5 was performed using a machine learning algorithm based on the Prank Web and DeepSite chemoinformatic tool. The analysis revealed that several amino acids of AzrBmH2 interacted with the tested dyes, indicating the presence of distinct ligand-binding sites for AzrBmH2-dye complexes. The binding affinity for AzrBmH21, AzrBmH22/3, and AzrBmH24/5 ranged from − 9.4 to -5.5 kcal/mol, -9.2 to -5.4 kcal/mol, and − 9.0 to -5.4 kcal/mol, respectively. Each complex was stabilized by a minimum of 0–5 hydrogen bonds. MD simulations revealed stable AzrBmH2-dye complexes (with RMSD 0.15–0.42 nm, RMSF 0.05–0.48 nm, Rg 1.75–1.88 nm). MMPBSA calculations indicated that the AzrBmH2-dye complexes, except for AzrBmH2-malachite green, exhibited the lowest binding energy (-191.05 ± 7.08 to 314.19 ± 6.88 kcal/mol). The AzrBmH2-malachite green complex showed a prevalence of hydrophobic interactions (-268.25 ± 12.25 to -418.92 ± 29.45 kcal/mol) through van der Waals forces. This study highlights the potential role of enzymes, specifically azoreductases from Bacillus megaterium H2, in predicting the decolorization of commercial dyes. These findings contribute to our understanding of enzyme mechanisms in bioremediation and for biotechnological applications.

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“…The disease’s alarming increase in global incidence over the past few decades has made it a prominent public health issue in the 21st century. , One of the most common types of DM is noninsulin-dependent diabetes, commonly known to be type 2 diabetes (T2DM), which happens due to insulin resistance. Four hundred twenty-two million people worldwide were estimated to have diabetes as of 2014, up from 108 million in 1980 in the WHO report. , Furthermore, DM currently ranks as the seventh leading disease in mortality rate worldwide. , Individuals diagnosed with diabetes may incur various issues as a result of blood vessel impairment and harm to multiple body organs, such as the heart, nerves, kidneys, and eyes. − The most chemotherapeutic strategy used for managing DM is to regulate postprandial blood glucose levels by blocking the primary enzymes that are responsible for carbohydrate hydrolysis such as α-glucosidase and α-amylase enzymes. − Both enzymes are essential for the decomposition of disaccharides and sugars, as well as the assimilation of glucose. In addition, the enzymes have the ability to break down polysaccharides into glucose and maltose; through this process, the body glucose level and the negative impact of the disease increase. , Therefore, it is thought that inhibiting α-glucosidase and α-amylase is a useful tactic in the management of T2DM.…”

Section: Introductionmentioning

confidence: 99%

“… 7 − 13 The most chemotherapeutic strategy used for managing DM is to regulate postprandial blood glucose levels by blocking the primary enzymes that are responsible for carbohydrate hydrolysis such as α-glucosidase and α-amylase enzymes. 14 − 16 Both enzymes are essential for the decomposition of disaccharides and sugars, as well as the assimilation of glucose. In addition, the enzymes have the ability to break down polysaccharides into glucose and maltose; through this process, the body glucose level and the negative impact of the disease increase.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Novel and Selective Schiff Base Inhibitors as a Key for Drug Synthesis, Molecular Docking, and Pharmacological Evaluation

Khan,

Rehman,

Rasheed

et al. 2024

ACS Omega

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Diabetes mellitus (DM) is a chronic disorder and still a challenge throughout the world, and therefore the search for safe and effective inhibitors for αamylase and α-glucosidase is increasing day by day. In this work, we try to carry out the synthesis, modification, and computer-aided results of and biological research on thiadiazole-based Schiff base derivatives and evaluate their in vitro α-amylase and αglucosidase inhibitory potential (1−15). In the current series, all of the synthesized analogues were shown to have potential inhibitory effects on targeted enzymes. The IC 50 values for α-amylase values ranged from 20.10 ± 0.40 to 0.80 ± 0.05 μM, compared with the standard drug acarbose having an IC 50 value of 10.30 ± 0.20 μM, while for αglucosidase, the IC 50 values ranged from 20.10 ± 0.50 to 1.20 ± 0.10 μM, compared to acarbose with an IC 50 value of 9.80 ± 0.20 μM. For better understanding, a SAR investigation was undertaken. In this series, nine scaffolds (1, 2, 3, 6, 9, 10, 11, 13, and 15) were more active than the reference drug and the docking parameter RMSD values for α-

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Molecular dynamics simulations reveal the inhibitory mechanism of Withanolide A against α-glucosidase and α-amylase

Cited by 10 publications

References 68 publications

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

Bioinformatics analysis and molecular dynamics simulations of azoreductases (AzrBmH2) from Bacillus megaterium H2 for the decolorization of commercial dyes

Discovery of Novel and Selective Schiff Base Inhibitors as a Key for Drug Synthesis, Molecular Docking, and Pharmacological Evaluation

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