• Journal of Life Science
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• v.33 no.11
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• pp.876-886
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• 2023

In some cases of head and neck cancers (HNC), surgical interventions may result in the loss of organs and/or changes to their functions, thereby significantly affecting the patient's quality of life. As a result, the surgical treatment of HNC patients is often limited to specific cases, and alternative treatment modalities, such as chemotherapy, are considered. However, serious adverse effects caused by chemotherapy, such as severe nausea and vomiting, necessitate the need for the development of adjunctive methods to minimize patient suffering. Chuanxiong, Ligusticum chuanxiong (L. chuanxiong), is a natural herb used in Eastern medicine to treat cerebrovascular disorders and headaches. This study aimed to predict the effect and potential of L. chuanxiong as an auxiliary anticancer drug through network-based pharmacology and molecular docking analysis. The study results showed that 40 out of 41 genes of L. chuanxiong shared common targets of HNC and their proteins could be used to target HNC cells to prevent cancer progression. The results of the functional enrichment analysis confirmed that L. chuanxiong is associated with the neuroactive-ligand metabolism and neurotransmitter pathways, indicating its potential medicinal value as an adjuvant in HNC treatment. Lastly, our findings demonstrated that the active ingredient of L. chuanxiong, (Z)-Ligustilide, has the ATP binding site of heat shock protein 90, a protein known to promote the activation of cancer cells. These results suggest that L. chuanxiong is a promising candidate for developing auxiliary anticancer drugs, and further research could potentially lead to the discovery of newer and safer anti-cancer agents.

• Proceedings of KOSOMES biannual meeting
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• 2017.11a
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• pp.49-49
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• 2017

• Journal of Integrative Natural Science
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• v.15 no.4
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• pp.187-194
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• 2022

Protein Arginine Methyltransferase 5 (PRMT5), a significant member of the PRMT family, is a promising anticancer target. In this study, novel small compounds that act against the PRMT5 target are found by combining virtual screening with ChEMBL database medicines and Density Functional Theory. The ChEMBL database compounds were screened to retrieve the hit molecules, which further subjected for DFT analysis. Finally we have evaluated that ChEMBL- approved drugs such as Lifitegrast, Abiraterone acetate and Solifenacin may be potential inhibitors for PRMT5.

• Journal of Applied Biological Chemistry
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• v.54 no.1
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• pp.56-62
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• 2011

Molecular docking of polyhydroxy substituted flavone analogues (1-25) as substrate molecules to the active site of tyrosinase (PDB ID: Deoxy-form (2ZMX) & Oxy-form (1WX2)) and Free-Wilson analysis were studied to understand the roles of hydroxyl substituents ($R_1-R_9$) in substrate molecules for the tyrosinase inhibitory activation. It is founded from Free-Wilson analysis that the $R_1$=hydroxyl among $R_1-R_9$ substituents had the strongest influence on the tyrosinase inhibitory activity. H-bonds between the hydroxyl substituents of substrate molecules and amino acid residues in the active site of tyrosinase were contributed to make a stable substrate-receptor complex compound. Particularly, it is proposed from the findings that the noncompetitive inhibitory activation would take place via H-bonding between peroxide oxygen (Per404) atom in the active site of tyrosinase and the hydroxyl substituents in substrate molecule.

• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3199-3205
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• 2013

The inclusion behavior of sulfobutylether-${\beta}$-cyclodextrin (SBE-${\beta}$-CD) with perphenazine (PPH) was first studied by flow injection (FI)-chemiluminescence (CL) analysis with proposed $lg[(I_0-I_s)/I_s]=lgK_{P-CD}+nlg[C_{PPH}]$ model and molecular docking. Results showed that a 1:1 complex of SBE-${\beta}$-CD/PPH could online form, with the formation constant $K_{P-CD}$ of $2.57{\times}10^7Lmol^{-1}$ at 298 K. The thermodynamic parameters showed that the inclusion behavior of SBE-${\beta}$-CD/PPH was a spontaneous process by hydrophobic interaction. The molecular docking results revealed PPH entered into the larger cavity of SBE-${\beta}$-CD with two hydrogen bonds. Based on the linear relationship of the decrement of luminol/SBE-${\beta}$-CD/PPH CL intensity against the logarithm of PPH concentration ranging from 0.03 to 30.0 ng $mL^{-1}$, the present FI-CL analysis using luminol/SBE-${\beta}$-CD/PPH system was successfully applied to PPH determination in biological fluids and tablets with recoveries from 94.5 to 105.6% and RSDs less than 2.6% (n = 5).

• Korean Journal of Microbiology
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• v.39 no.3
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• pp.141-147
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• 2003

The simultaneous expression levels of antifungal activity related genes was analyzed by DNA microarray. We constructed DNA chips contained 2,000 randomly digested genome spots of the antifungal bacterium of Bacillus lentimorbus WJ5 and compared its quantitative aspect with 7 antifungal activity deficient mutants induced by gamma radiation ($^{60}Co$). From the analysis of microarray hybridization by the Gene Cluster (Michael Eisen, Stanford Univ.), totally 408 genes were expressed and 20 genes among them were significantly suppressed in mutants. pbuX (xanthine permease, K222), ywbA (phosphotransferase system enzyme II, K393), ptsG (PTS glucose specific enzyme II ABC component, K877), yufO (ABC transporter (ATP-binding protein), K130l), and ftsY (signal recognition particle (docking protein), K868) were simultaneously down-regulated in all mutants. It suggested that they were supposed to be related to the antifungal activity of B. lentimorbus WJ5.

• Genomics & Informatics
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• v.12 no.4
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• pp.268-275
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• 2014

The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis.

• Natural Product Sciences
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• v.25 no.1
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• pp.28-33
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• 2019

A popular approach for the study of estrogen receptor ${\alpha}$ inhibition is to investigate the protein-protein interaction between the estrogen receptor (ER) and the coactivator surface. In our study, we investigated phytochemicals from Rubus coreanus that were able to disrupt $ER{\alpha}$ and coactivator interaction with an $ER{\alpha}$ antagonist. The E-screen assay and molecular docking analysis were performed to evaluate the effects of the estrogenic activity of R. coreanus extract and its constituents on the MCF-7 human breast cancer cell line. At $100{\mu}g/mL$, R. coreanus extract significantly stimulated cell proliferation ($574.57{\pm}8.56%$). Sanguiin H6, which was isolated from R. coreanus, demonstrated the strongest affinity for the $ER{\alpha}$ coactivator-binding site in molecular docking analysis, with a binding energy of -250.149. The initial results of the study indicated that sanguiin H6 contributed to the estrogenic activity of R. coreanus through the activation of the $ER{\alpha}$ coactivator-binding site.

• Genomics & Informatics
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• v.21 no.3
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• pp.32.1-32.11
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• 2023

Resistance to anti-tuberculosis drugs, especially ethambutol (EMB), has been widely reported worldwide. EMB resistance is caused by mutations in the embB gene, which encodes the arabinosyl transferase enzyme. This study aimed to detect mutations in the embB gene of Mycobacterium tuberculosis from Papua and to evaluate their impact on the effectiveness of EMB. We analyzed 20 samples of M. tuberculosis culture that had undergone whole-genome sequencing, of which 19 samples were of sufficient quality for further bioinformatics analysis. Mutation analysis was performed using TBProfiler, which identified M306L, M306V, D1024N, and E378A mutations. In sample TB035, the M306L mutation was present along with E378A. The binding affinity of EMB to arabinosyl transferase was calculated using AutoDock Vina. The molecular docking results revealed that all mutants demonstrated an increased binding affinity to EMB compared to the native protein (-0.948 kcal/mol). The presence of the M306L mutation, when coexisting with E378A, resulted in a slight increase in binding affinity compared to the M306L mutation alone. The molecular dynamics simulation results indicated that the M306L, M306L + E378A, M306V, and E378A mutants decreased protein stability. Conversely, the D1024N mutant exhibited stability comparable to the native protein. In conclusion, this study suggests that the M306L, M306L + E378A, M306V, and E378A mutations may contribute to EMB resistance, while the D1024N mutation may be consistent with continued susceptibility to EMB.

• Journal of Ginseng Research
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• v.48 no.4
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• pp.395-404
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• 2024

Background: Ginsenoside Rg₁ (Rg₁) is one of the main active components in Chinese medicines, Panax ginseng and Panax notoginseng. Research has shown that Rg₁ has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood. Methods: Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV-Vis and fluorescence spectra) techniques, potential targets and pathways for Rg₁ against myocardial ischemia (MI) were screened and explored. Results: An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg₁ against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg₁ intervention on H9c2 cells injured by H₂O₂ showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg₁ on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg₁ was also evaluated. Conclusion: Rg₁ can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg₁, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.