NETWORK PHARMACOLOGY AND MOLECULAR DOCKING-BASED PREDICTION OF PHARMACOLOGICAL PROPERTIES OF OSTHOLE
DOI:
https://doi.org/10.22159/ijms.2023.v11i4.47981Keywords:
Osthole, Docking, pharmacology, ADMETAbstract
Objectives: In this study, the term called network pharmacology (NP) process which was used to understand the underlying mechanism of the pharmacological properties of Osthole. NP is developed that is used to understand drug actions and interactions with multiple targets and it is also capable of completely articulating the complexity between diseases and medications. The research was carried out for the identification of diverse drug-target interactions using NP to discover novel medications for difficult conditions such as Parkinson’s, Cancer, and Alzheimer’s disease and many more. Osthole was used for prediction which could be used in the pharmaceutical background.
Methods: To understand the binding affinity of Osthole with the corresponding target proteins, it was analyzed. It was determined from the pathway by which diseases can be caused, such as cancer and Alzheimer’s disease. A PyRx tool was used to carry out the molecular docking. For this research, structures of protein and phytocompounds were retrieved from UniProtKB and PubChem. Furthermore, along with the help of BIOVIA discovery studio software, the protein structure was analyzed and ADMET screening was done to evaluate the Osthole pharmacological properties.
Results: The ligands were retrieved for Osthole from PubChem, then target prediction was carried out where it showed 100 potential targets. The protein-protein network and interaction were done using the STRING database, in which it showed that these CREBBP, IDO1, and MAPK8 targets have maximum interactions followed by the Gene functional analysis, that is, go function and KEGG pathway. The molecular docking was carried out using PyRx in which 4U72 showed the best binding affinity to Osthole. Furthermore, visualization was done using BIOVIA Discovery Studio, which provided the 3D and 2D visualization.
Conclusion: According to the results obtained for molecular docking, these target proteins have pharmacological effects which can be considered as suggestions for the investigation of the pharmacological mechanism of Osthole.
References
Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 2008;4:682-90.
Alzarea SI, Qasim S, Uttra AM, Khan YH, Aljoufi FA, Ahmed S
dentistry/pubchem [Last accessed on 2023 Mar 05].
Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, et al. PubChem substance and compound databases. Nucleic Acids Res 2015;44:D1202-13.
Ge SX, Jung D, Yao R. ShinyGO: A graphical gene-set enrichment tool for animals and plants. Bioinformatics 2019;36:2628-9.
Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods Mol Biol 2014;1263:243-50.
Kondapuram SK, Sarvagalla S, Coumar MS. Docking-based virtual screening using pyrx tool: Autophagy target VPS34 as a case study. In: Molecular Docking for Computer-aided Drug Design. Cambridge: Academic Press; 2021. p. 463-77.
Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, et al. ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res 2021;49:W5-14.
Dong J, Wang NN, Yao ZJ, Zhang L, Cheng Y, Ouyang D, et al. ADMETlab: A platform for systematic ADMET evaluation based on a comprehensively collected ADMET database. J Cheminform 2018;10:29.
Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, et al. The string database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/ measurement sets. Nucleic Acids Res 2020;49:D605-12.
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta- Cepas J, et al. String V11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 2018;47:D607-13.
Daina A, Michielin O, Zoete V. SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res 2019;47:W357-64.
Gfeller D, Grosdidier A, Wirth M, Daina A, Michielin O, Zoete V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic Acids Res 2014;42:W32-8.
Xu X, Lai Y, Hua ZC. Apoptosis and apoptotic body: Disease message and therapeutic target potentials. Biosci Rep 2019;39.
Monin L, Gaffen SL. Interleukin 17 family cytokines: Signaling mechanisms, biological activities, and therapeutic implications. Cold Spring Harb Perspect Biol 2017;10:a028522.
Cell Cycle; (n.d.). Available from: https://www.genome.gov/ genetics-glossary/cell-cycle#:~:text=a%20cell%20cycle%20is%20 a,mitosis%2c%20and%20completes%20its%20division [Last accessed on 2023 Mar 05].
Ontology. Royal Society of Chemistry; (n.d.). Available from: https://www.rsc.org/publishing/journals/prospect/ontology. asp?id=GO%3A0009166&msid=b908681a [Last accessed on 2023 Mar 05].
Eskandari N, Mirmosayyeb O, Bordbari G, Bastan R, Yousefi Z, Andalib A. A short review on structure and role of cyclic-3’,5’- adenosine monophosphate-specific phosphodiesterase 4 as a treatment tool. J Res Pharm Pract 2015;4:175-81.
Carbonate Dehydratase. Carbonate Dehydratase-an Overview ScienceDirect Topics; (n.d.). Available from: https://www.sciencedirect. com/topics/pharmacology-toxicology-and-pharmaceutical-science/ carbonate-dehydratase [Last accessed on 2023 Mar 05].
Radhakrishnan A, Raju R, Tuladhar N, Subbannayya T, Thomas JK, Goel R, et al. A pathway map of prolactin signaling. J Cell Commun Signal 2012;6:169-73.
Zhang Z, Xiahou Z, Wu W, Song Y. Nitrogen metabolism disorder accelerates occurrence and development of lung adenocarcinoma: A bioinformatic analysis and in vitro experiments. Front Oncol 2022;12:916777.
Lee D, Hong JH. The fundamental role of bicarbonate transporters and associated carbonic anhydrase enzymes in maintaining ion and pH homeostasis in non-secretory organs. Int J Mol Sci 2020;21:339.
Fajardo AM, Piazza GA, Tinsley HN. The role of cyclic nucleotide signaling pathways in cancer: Targets for prevention and treatment. Cancers (Basel) 2014;6:436-58.
Kowtharapu BS, Damaraju J, Singh NK, Ziebart J, Bader R, Koczan D, et al. Analysis of the differential gene and protein expression profiles of corneal epithelial cells stimulated with alternating current electric fields. Genes (Basel) 2021;12:299.
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