Mechanistic inhibition of gastric cancer-associated bacteria Helicobacter pylori by selected phytocompounds: A new cutting-edge computational approach

Akash, Shopnil; Bayıl, Imren; Mahmood, Sajjat; Mukerjee, Nobendu; Mili, Tamanna Akter; Dhama, Kuldeep; Rahman, Md Anisur; Maitra, Swastika; Mohany, Mohamed; Al-Rejaie, Salim S.; Ali, Nemat; Semwal, Prabhakar; Sharma, Rohit

doi:10.1016/j.heliyon.2023.e20670

Cited by 11 publications

(4 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The simulations, lasting 100 ns in a periodic water box, utilized the CHARMM36 force field and the Gromacs version 2020 software package [ 59 , 60 ]. The complexes were placed within a rectangular box with a buffer distance of 10 in each direction [ 61 ]. Subsequently, the box was solvated by adding TIP3P water molecules.…”

Section: Methodsmentioning

confidence: 99%

Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions

Ja’afaru,

Uzairu,

Bayil

et al. 2024

PLoS ONE

Self Cite

View full text Add to dashboard Cite

Schistosomiasis is a neglected tropical disease which imposes a considerable and enduring impact on affected regions, leading to persistent morbidity, hindering child development, diminishing productivity, and imposing economic burdens. Due to the emergence of drug resistance and limited management options, there is need to develop additional effective inhibitors for schistosomiasis. In view of this, quantitative structure-activity relationship studies, molecular docking, molecular dynamics simulations, drug-likeness and pharmacokinetics predictions were applied to 39 Schistosoma mansoni Thioredoxin Glutathione Reductase (SmTGR) inhibitors. The chosen QSAR model demonstrated robust statistical parameters, including an R2 of 0.798, R2adj of 0.767, Q2cv of 0.681, LOF of 0.930, R2test of 0.776, and cR2p of 0.746, confirming its reliability. The most active derivative (compound 40) was identified as a lead candidate for the development of new potential non-covalent inhibitors through ligand-based design. Subsequently, 12 novel compounds (40a-40l) were designed with enhanced anti-schistosomiasis activity and binding affinity. Molecular docking studies revealed strong and stable interactions, including hydrogen bonding, between the designed compounds and the target receptor. Molecular dynamics simulations over 100 nanoseconds and MM-PBSA free binding energy (ΔGbind) calculations validated the stability of the two best-designed molecules. Furthermore, drug-likeness and pharmacokinetics prediction analyses affirmed the potential of these designed compounds, suggesting their promise as innovative agents for the treatment of schistosomiasis.

show abstract

Section: Methodsmentioning

confidence: 99%

Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions

Ja’afaru,

Uzairu,

Bayil

et al. 2024

PLoS ONE

Self Cite

View full text Add to dashboard Cite

show abstract

“…Protein Retrieval. The protein structures utilized in this study included mutated variants of KRAS at codons 12 and 13, the wildtype KRas structure (PDB ID: 6mbu) 7 namely G12C (PDB ID: 6USZ), 8 G12D (PDB ID: 7xkj), 6 G12V (PDB ID: 7c40), 9 and G13D (PDB ID: 6e6f), 10 sourced from the Protein Data Bank (PDB) (Berman et al, 2000) for comparative analysis. These structures were chosen based on their relevance to oncogenic transformation and their availability in the PDB (Figure 1).…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Exploring KRas Protein Dynamics: An Integrated Molecular Dynamics Analysis of KRas Wild and Mutant Variants

Mir,

Nayak,

Aljarba

et al. 2024

ACS Omega

View full text Add to dashboard Cite

This study employs a comprehensive approach combining protein retrieval, sequence alignment, and molecular dynamics simulations to investigate the structural dynamics and stability of wild-type KRas and its mutated variants (G12C, G12D, G12V, and G13D). The selected protein structures were retrieved from the Protein Data Bank (PDB) and prepared by using visual molecular dynamics (VMD) software. Sequence alignment using Clustal Omega provided a detailed comparison of the amino acid sequences, focusing on key mutation sites. Molecular dynamics simulations, performed with Gromacs, revealed distinct conformational changes and stability patterns in the wild-type and mutated KRas proteins over 100 ns. Clustering analysis identified higher conformational changes in the second α-helix of the mutated variants. The root-mean-square deviation (RMSD) distribution analysis showed variant-specific conformational dynamics, with G12V and G12D exhibiting slightly higher average RMSD values. Furthermore, clustering and RMSD analyses of specific amino acid residues (12, 13, 51, and 118) highlighted their roles in maintaining overall stability and influencing structural dynamics. The results indicate that mutations at positions 12 and 13 disrupt normal cycling between wild and mutated variants, leading to the persistent activation of KRas. Additionally, principal component analysis (PCA) elucidated unique conformational dynamics in mutated variants. Free energy landscape (FEL) analysis revealed alterations in the thermodynamic stability of mutated variants compared with the wild type. Overall, this study provides a detailed understanding of the structural changes associated with oncogenic mutations in KRas, offering insights crucial for targeted therapeutic strategies in KRas-driven cancers.

show abstract

“…Helicobacter pylori is a Gram-negative bacterium. It affects more than one half of the world population, and it is an etiologic agent of the peptic acid disease in 10–20% of infected individuals, while 1–2% of these persons entertain the risk of developing gastric cancer or mucosa-associated lymphoid tissue (MALT); it exclusively colonizes the gastric mucosa [ 94 ]. Abundant sulforaphane (SFN) in crucifers induces a variety of antioxidants in the cells and organs against oxidative stress, which can contribute to the chemoprotection; in the GI tract of mice, it induces antioxidant enzymes and protects the GI mucosa against damage conditioned by Helicobacter pylori and anti-inflammatory non-steroidal substances (NSAIDS) [ 95 ].…”

Section: Function Of the Phytochemicals In The Organismmentioning

confidence: 99%

Phytochemicals and Their Usefulness in the Maintenance of Health

Rodríguez-Negrete,

Morales-González,

Madrigal-Santillán

et al. 2024

Plants

View full text Add to dashboard Cite

Inflammation is the immune system’s first biological response to infection, injury, or irritation. Evidence suggests that the anti-inflammatory effect is mediated by the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ, as well as the non-cytokine mediator, prostaglandin E2. Currently, the mechanism of action and clinical usefulness of phytochemicals is known; their action on the activity of cytokines, free radicals, and oxidative stress. The latter are of great relevance in the development of diseases, such that the evidence collected demonstrates the beneficial effects of phytochemicals in maintaining health. Epidemiological evidence indicates that regular consumption of fruits and vegetables is related to a low risk of developing cancer and other chronic diseases.

show abstract

Mechanistic inhibition of gastric cancer-associated bacteria Helicobacter pylori by selected phytocompounds: A new cutting-edge computational approach

Cited by 11 publications

References 66 publications

Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions

Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions

Exploring KRas Protein Dynamics: An Integrated Molecular Dynamics Analysis of KRas Wild and Mutant Variants

Phytochemicals and Their Usefulness in the Maintenance of Health

Contact Info

Product

Resources

About