Investigative on the Molecular Mechanism of Licorice Flavonoids Anti-Melanoma by Network Pharmacology, 3D/2D-QSAR, Molecular Docking, and Molecular Dynamics Simulation

Hu, Yi; Wu, Yufan; Jiang, Cuiping; Wang, Zhuxian; Shen, Chunyan; Zhu, Zhaoming; Li, Hui; Zeng, Quanfu; Xue, Yi; Wang, Yuan; Liu, Li; Yi, Yankui; Zhu, Hongxia; Liu, Qiang

doi:10.3389/fchem.2022.843970

Cited by 15 publications

(12 citation statements)

References 47 publications

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“…Dynamic simulation studies and trajectory analysis were performed to prove the stability of the interaction between 4b and eIF4E compared to reference Ribavirin and natural cap m7G Figure shows the total energy versus time range of 16–24 ps of free protein expressed as −(7480–7500) kcal/mol.…”

Section: Resultsmentioning

confidence: 99%

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Newly Synthesized Anticancer Purine Derivatives Inhibiting p-EIF4E Using Surface-Modified Lipid Nanovesicles

Attia,

Ewida,

Khaled

et al. 2023

ACS Omega

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Translation of mRNA is one of the processes adopted by cancer cells to maintain survival via phosphorylated (p)-eIF4E overexpression. Once p-eIF4E binds to the cap structure of mRNA, it advocates a nonstop translation process. In this regard, 15 new-based GMP analogs were synthesized to target eIF4E and restrain its binding to cap mRNA. The compounds were tested against three types of cancer cell lines: Caco-2, HepG-2, MCF-7, and normal kidney cells (Vero cells). Most of the compounds showed high potency against breast cancer cells (MCF-7), characterized by the highest cancer type for overexpression of p-eIF4E. Compound 4b was found to be the most active against three cell lines, colon (Caco-2), hepatic (HepG-2), and breast (MCF-7), with positive IC 50 values of 31.40, 27.15, and 21.71 μM, respectively. Then, chitosan-coated niosomes loaded with compound 4b (Cs/4b-NSs) were developed (as kinetically enhanced molecules) to improve the anticancer effects further. The prepared Cs/4b-NSs showed pronounced cytotoxicity compared to the free 4b against Caco2, Hepg2, and MCF-7 with IC 50 values of 16.15, 26.66, and 6.90 μM, respectively. Then, the expression of both the phosphorylated and nonphosphorylated western blot techniques was conducted on MCF-7 cells treated with the most active compounds (based on the obtained IC 50 values) to determine the total protein expression of both eIF4E and p-eIF4e. Interestingly, the selected most active compounds displayed 35.8−40.7% inhibition of p-eIF4E expression when evaluated on MCF-7 compared to Ribavirin (positive control). CS/4b-NSs showed the best inhibition (40.7%). The findings of the present joint in silico molecular docking, simulation dynamic studies, and experimental investigation suggest the potential use of niosomal nanovesicles as a promising nanocarrier for the targeted delivery of the newly synthesized compound 4b to eukaryotic initiation factor 4E. These outcomes support the possible use of Cs/4b-NSs in targeted cancer therapy.

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Section: Resultsmentioning

confidence: 99%

“…On the other hand, the equilibration phase was set with a simulation time of 10 ps and an interval of 2 ps. The Implicit Solvent Model was set to Generalized Born with Simple Switching (GBSW), and the dynamics integrator protocol used LeapfroyVerlet …”

Section: Methodsmentioning

confidence: 99%

Newly Synthesized Anticancer Purine Derivatives Inhibiting p-EIF4E Using Surface-Modified Lipid Nanovesicles

Attia,

Ewida,

Khaled

et al. 2023

ACS Omega

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“…Actinomycin D exhibited a strong binding energy with a score of 165.079. A LibDockScore of ≥90 indicates a strong affinity between the ligand and receptor, facilitating ligand binding (Hu et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics

Liu

Tian

et al. 2023

Front. Microbiol.

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IntroductionVibrio parahaemolyticus is a foodborne pathogen commonly found in seafood, and drug resistance poses significant challenges to its control. This study aimed to identify novel drug targets for antibacterial drug discovery.MethodsTo identify drug targets, we performed a pan-genome analysis on 58 strains of V. parahaemolyticus genomes to obtain core genes. Subsequently, subtractive proteomics and physiochemical checks were conducted on the core proteins to identify potential therapeutic targets. Molecular docking was then employed to screen for anti-V. parahaemolyticus compounds using a in-house compound library of Streptomyces parvus, chosen based on binding energy. The anti-V. parahaemolyticus efficacy of the identified compounds was further validated through a series of experimental tests.Results and DiscussionPangenome analysis of 58 V. parahaemolyticus genomes revealed that there were 1,392 core genes. After Subtractive proteomics and physiochemical checks, Flagellar motor switch protein FliN was selected as a therapeutic target against V. parahaemolyticus. FliN was modeled and docked with Streptomyces parvus source compounds, and Actinomycin D was identified as a potential anti-V. parahaemolyticus agent with a strong binding energy. Experimental verification confirmed its effectiveness in killing V. parahaemolyticus and significantly inhibiting biofilm formation and motility. This study is the first to use pan-genome and subtractive proteomics to identify new antimicrobial targets for V. parahaemolyticus and to identify the anti-V. parahaemolyticus effect of Actinomycin D. These findings suggest potential avenues for the development of new antibacterial drugs to control V. parahaemolyticus infections.

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“…Molecular Dynamics simulations (MDS) were further conducted to investigate the stability of small molecule ligands in proteins by the “Standard Dynamics Cascade” unit of Discovery Studio2019 software for ligand-protein complexes with the lowest binding affinity after molecular docking ( Hu et al, 2022 ). The ligand-protein complex was placed in a solvent chamber, filled with water molecules and stabilized the electrically neutral system with Cl− and Na+.…”

Section: Methodsmentioning

confidence: 99%

Exploring the mechanism of Alisma orientale for the treatment of pregnancy induced hypertension and potential hepato-nephrotoxicity by using network pharmacology, network toxicology, molecular docking and molecular dynamics simulation

Liao

Ding

et al. 2022

Front. Pharmacol.

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Background: Pregnancy-induced Hypertension (PIH) is a disease that causes serious maternal and fetal morbidity and mortality. Alisma Orientale (AO) has a long history of use as traditional Chinese medicine therapy for PIH. This study explores its potential mechanism and biosafety based on network pharmacology, network toxicology, molecular docking and molecular dynamics simulation.Methods: Compounds of AO were screened in TCMSP, TCM-ID, TCM@Taiwan, BATMAN, TOXNET and CTD database; PharmMapper and SwissTargetPrediction, GeneCards, DisGeNET and OMIM databases were used to predict the targets of AO anti-PIH. The protein-protein interaction analysis and the KEGG/GO enrichment analysis were applied by STRING and Metascape databases, respectively. Then, we constructed the “herb-compound-target-pathway-disease” map in Cytoscape software to show the core regulatory network. Finally, molecular docking and molecular dynamics simulation were applied to analyze binding affinity and reliability. The same procedure was conducted for network toxicology to illustrate the mechanisms of AO hepatotoxicity and nephrotoxicity.Results: 29 compounds with 78 potential targets associated with the therapeutic effect of AO on PIH, 10 compounds with 117 and 111 targets associated with AO induced hepatotoxicity and nephrotoxicity were obtained, respectively. The PPI network analysis showed that core therapeutic targets were IGF, MAPK1, AKT1 and EGFR, while PPARG and TNF were toxicity-related targets. Besides, GO/KEGG enrichment analysis showed that AO might modulate the PI3K-AKT and MAPK pathways in treating PIH and mainly interfere with the lipid and atherosclerosis pathways to induce liver and kidney injury. The “herb-compound-target-pathway-disease” network showed that triterpenoids were the main therapeutic compounds, such as Alisol B 23-Acetate and Alisol C, while emodin was the main toxic compounds. The results of molecular docking and molecular dynamics simulation also showed good binding affinity between core compounds and targets.Conclusion: This research illustrated the mechanism underlying the therapeutic effects of AO against PIH and AO induced hepato-nephrotoxicity. However, further experimental verification is warranted for optimal use of AO during clinical practice.

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Investigative on the Molecular Mechanism of Licorice Flavonoids Anti-Melanoma by Network Pharmacology, 3D/2D-QSAR, Molecular Docking, and Molecular Dynamics Simulation

Cited by 15 publications

References 47 publications

Newly Synthesized Anticancer Purine Derivatives Inhibiting p-EIF4E Using Surface-Modified Lipid Nanovesicles

Newly Synthesized Anticancer Purine Derivatives Inhibiting p-EIF4E Using Surface-Modified Lipid Nanovesicles

Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics

Exploring the mechanism of Alisma orientale for the treatment of pregnancy induced hypertension and potential hepato-nephrotoxicity by using network pharmacology, network toxicology, molecular docking and molecular dynamics simulation

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