• Journal of Integrative Natural Science
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• v.15 no.4
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• pp.179-186
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• 2022

The c-Jun N-terminal kinase (JNK3) play major role in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, cerebral ischemia and other Central Nervous System disorders. Since JNK3 is primarily stated in the brain and stimulated by stress-stimuli, this situation is conceivable that inhibiting JNK3 could be a possible treatment for the mechanisms underlying neurodegenerative diseases. In this study drugs from Zinc15 database were screened to identify the JNK3 inhibitors by Molecular docking and Density functional theory approach. Molecular docking was done by Autodock vina and the ligands were selected based on the binding affinity. Our results identified top ten novel ligands as potential inhibitors against JNK3. Molecular docking revealed that Venetoclax, Fosaprepitant and Avapritinib exhibited better binding affinity and interacting with proposed binding site residues of JNK3. Density functional theory was used to compute the values for energy gap, lowest unoccupied molecular orbital (LUMO), and highest occupied molecular orbital (HOMO). The results of Density functional theory study showed that Venetoclax, Fosaprepitant and Avapritinib serves as a lead compound for the development of JNK3 small molecule inhibitors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10345-10350
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• 2015

Background: Punica granatum (family: Lythraceae) is mainly found in Iran, which is considered to be its primary centre of origin. Studies on pomegranate peel have revealed antioxidant, anti-inflammatory, anti-angiogenesis activities, with prevention of premature aging and reducing inflammation. In addition to this it is also useful in treating various diseases like diabetes, maintaining blood pressure and treatment of neoplasms such as prostate and breast cancer. Objectives: In this study we identified anti-cancer targets of active compounds like corilagin (tannins), quercetin (flavonoids) and pseudopelletierine (alkaloids) present in pomegranate peel by employing dual reverse screening and binding analysis. Materials and Methods: The potent targets of the pomegranate peel were annotated by the PharmMapper and ReverseScreen 3D, then compared with targets identified from different Bioassay databases (NPACT and HIT's). Docking was then further employed using AutoDock pyrx and validated through discovery studio for studying molecular interactions. Results: A number of potent anti-cancerous targets were attained from the PharmMapper server according to their fit score and from ReverseScreen 3D server according to decreasing 3D scores. Conclusion: The identified targets now need to be further validated through in vitro and in vivo studies.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.95-95
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• 2018

Uric acid is the end product of purine metabolism in human body, originating from hypoxanthine after enzyme catalysis by Xanthine oxidase (XOD). Hyperuricemia results as a result of either over-generation of uric acid or a reduction in its excretion. In silico modelling methods such as Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) prediction, Autodock 4.2.6 program were used to study the potential inhibitory compounds of XOD. Also we investigated the inhibition of XOD activity by using the extracts of Dendropanax morbifera and Rubus coreanus Miq spectrophotometrically. According to ADMET data, several compounds from D. morbifera and R. coreanus plants, were found to be more potent in inhibiting the XOD activity than allopurinol. XOD inhibitory activity is evaluated by quantifying the formation of uric acid by measuring the absorbance at 290 m ($A_{290}$).D. morbifera extract inhibited XOD activity at $250{\mu}g/ml$, however the extracts from R. coreanus has inhibited XOD activity at $25{\mu}g/ml$. The major compound of R. coreanus, ellagic acid significantly increased the inhibition rate from $9{\mu}g/ml$ and showed a 71% suppression rate at $15{\mu}g/ml$. Finally, these results suggested a potential inhibitory activities of the extracts from D. morbifera and R. coreanus Miq, but further research is needed to validate to ensure their safe usage as drug.

• Journal of Plant Biotechnology
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• v.48 no.4
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• pp.289-303
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• 2021

Covid-19 is an ongoing pandemic as we speak in 2022. This infectious disease is caused by the SARS-CoV-2 virus, which infects cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface. Thus, strategies that inhibit the binding of SARS-CoV-2 to the ACE2 receptor can stop this contagion. Hanjeli (Coix lacryma-jobi) essential oil contains many bioactive compounds, including dodecanoic acid; tetradecanoic acid; 7-Amino-8-imino-2-(2-imino-2H-chromen-3-yl); and 1,5,7,10-tetraaza-phen-9-one. These compounds suppress viral replication and may prevent Covid-19. Accordingly, this study assessed whether, these four limonoid compounds can block the ACE2 receptor. To this end, their physicochemical properties were predicted using Lipinski's "rule of five" on the SwissADME website, and their toxicity was assessed using the online tools ProTox and pkCSM. Additionally, their interactions with the ACE2 receptor were predicted via molecular docking using Autodock Vina. All the four compounds satisfied the "rule of five" and tetradecanoic acid was predicted to have a higher affinity than the comparison compound remdesivir and the original ligand of ACE2. Molecular docking results suggested that the compounds from hanjeli essential oil interact with the active site of the ACE2 receptor similarly as the original ligand and remdesivir. In conclusion, hanjeli essential oil contains compounds predicted hinder the interaction of SARS-CoV-2 with the ACE2 receptor. Accordingly, our data may facilitate the development of a phytomedical strategy against SARS-CoV-2 infection.

• Journal of Web Engineering
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• v.14 no.2
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• pp.265-283
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• 2022

Bauhinia scandens L. (Family: Fabaceae) is commonly used to treat cholera, diarrhea, asthma, and diabetes disorder in integrative medicine. This study aimed to screen the presence of phytochemicals (preliminary and UPLC-QTOF-M.S. analysis) and to examine the pharmacological activities of Bauhinia scandens L. stems (MEBS) stem extracts. Besides, in silico study was also implemented to elucidate the binding affinity and drug capability of the selected phytochemicals. In vivo anti diarrheal activity was investigated in mice models. In vitro, antibacterial and antifungal properties of MEBS against several pathogenic strains were evaluated using the disc diffusion method. In addition, in silico study has been employed using Discovery studio 2020, UCFS Chimera, PyRx autodock vina, and online tools. In the anti-diarrheal investigation, MEBS showed a significant dose-dependent inhibition rate in all three methods. The antibacterial and antifungal screening showed a remarkable zone of inhibition, of the diameter 14-26 mm and 12-28 mm, by MEBS. The present study revealed that MEBS has remarkable anti-diarrheal potential and is highly effective in wide-spectrum bacterial and fungal strains. Moreover, the in silico study validated the results of biological screenings. To conclude, MEBS is presumed to be a good source in treating diarrhea, bacterial and fungal infections.

• Journal of KIISE:Computing Practices and Letters
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• v.15 no.12
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• pp.881-890
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• 2009

To solve big problem in high energy physics or bioinformatics, it needs a large number of computing resources. But it hard to be provided by one grid environment. While user can submit each job by using it's own user interface in each grid environment, it may need many cost and efforts to manage several hundred jobs conserved in each grid environment separately. In this paper, to solve this problem we develop Ganga's Gridway backend and InterGrid backend. Therefore as we provide the same grid user interface between different grid environments. We developed a Gridway backend module that provide users with access to globus-based grid resources as well. We have also developed an InterGrid backend that allows users to submit jobs that have access to both glite-based resources and globus-based resources. In order to demonstrate the practicality of the new backend plugin modules, we have integrated the AutoDock application used by WISDOM project into Ganga as a new built-in application plugin for Ganga. And we preformed interoperability experiment between PRAGMA grid based on Globus and EGEE grid based on gLite.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.7-18
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• 2015

Objectives: Lawsone (1,4 naphthoquinone) is a non redox cycling compound that can be catalyzed by DT diaphorase (DTD) into 1,2,4-trihydroxynaphthalene (THN), which can generate reactive oxygen species by auto oxidation. The purpose of this study was to evaluate the toxicity of the phytomarker 1,4 naphthoquinone and its metabolite THN by using the molecular docking program AutoDock 4. Methods: The 3D structure of ligands such as hydrogen peroxide ($H_2O_2$), nitric oxide synthase (NOS), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) were drawn using hyperchem drawing tools and minimizing the energy of all pdb files with the help of hyperchem by $MM^+$ followed by a semi-empirical (PM3) method. The docking process was studied with ligand molecules to identify suitable dockings at protein binding sites through annealing and genetic simulation algorithms. The program auto dock tools (ADT) was released as an extension suite to the python molecular viewer used to prepare proteins and ligands. Grids centered on active sites were obtained with spacings of $54{\times}55{\times}56$, and a grid spacing of 0.503 was calculated. Comparisons of Global and Local Search Methods in Drug Docking were adopted to determine parameters; a maximum number of 250,000 energy evaluations, a maximum number of generations of 27,000, and mutation and crossover rates of 0.02 and 0.8 were used. The number of docking runs was set to 10. Results: Lawsone and THN can be considered to efficiently bind with NOS, CAT, GSH, GR, G6PDH and NADPH, which has been confirmed through hydrogen bond affinity with the respective amino acids. Conclusion: Naphthoquinone derivatives of lawsone, which can be metabolized into THN by a catalyst DTD, were examined. Lawsone and THN were found to be identically potent molecules for their affinities for selected proteins.

• Journal of the Korean Chemical Society
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• v.68 no.3
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• pp.151-159
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• 2024

Indian spices are well known for their numerous health benefits, flavour, taste, and colour. Recent Advancements in chemical technology have led to better extraction and identification of bioactive molecules (phytochemicals) from spices. The therapeutic effects of spices against diabetes, cardiac problems, and various cancers has been well established. The present in silico study aims to investigate the binding affinity of 29 phytochemicals from 11 Indian spices with two prominent proteins, BCL3 and CXCL10 involved in invasiveness and bone metastasis of breast cancer. The three-dimensional structures of 29 phytochemicals were extracted from PubChem database. Protein Data Bank was used to retrieve the 3D structures of BCL3 and CXCL10 proteins. The drug-likeness and other properties of compounds were analysed by ADME and Lipinski rule of five (RO5). All computational simulations were carried out using Autodock 4.0 on Windows platform. The proteins were set to be rigid and compounds were kept free to rotate. In-silico study demonstrated a strong complex formation (positive binding constants and negative binding energy ΔG) between all phytochemicals and target proteins. However, piperine and sesamolin demonstrated high binding constants with BCL3 (50.681 × 10³ mol^-1, 137.76 × 10³ mol^-1) and CXCL10 (98.71 × 10³ mol^-1, 861.7 × 10³ mol^-1), respectively. The potential of these two phytochemicals as a drug candidate was highlighted by their binding energy of -6.5 kcal mol^-1, -7.1 kcal mol^-1 with BCL3 and -6.9 kcal mol^-1, -8.2 kcal mol^-1 with CXCL10, respectively coupled with their favourable drug likeliness and pharmacokinetics properties. These findings underscore the potential of piperine and sesamolin as drug candidates for inhibiting invasiveness and regulating breast cancer metastasis. However, further validation through in vitro and in vivo studies is necessary to confirm the in silico results and evaluate their clinical potential.