{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T03:56:29Z","timestamp":1778126189940,"version":"3.51.4"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-75603-x","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T10:18:43Z","timestamp":1728382723000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["System biology-based assessment of the molecular mechanism of IMPHY000797 in Parkinson\u2019s disease: a network pharmacology and in-silico evaluation"],"prefix":"10.1038","volume":"14","author":[{"given":"Gomathy","family":"Subramanian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah Lalengzuali","family":"Fanai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jagdish","family":"Chand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheikh F.","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabry M.","family":"Attia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Talha Bin","family":"Emran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"75603_CR1","doi-asserted-by":"publisher","first-page":"130","DOI":"10.7324\/JAPS.2020.1010015","volume":"10","author":"AN El-Shorbagi","year":"2020","unstructured":"El-Shorbagi, A. N., Chaudhary, S., Alshemali, K. A., Alabdulrazzaq, R. F. & Alqahtani, F. Y. A comprehensive review on management of Parkinson\u2019s disease, inclusive of drug discovery and pharmacological approaches. J. Appl. Pharm. Sci. 10, 130\u2013150. https:\/\/doi.org\/10.7324\/JAPS.2020.1010015 (2020).","journal-title":"J. Appl. Pharm. Sci."},{"key":"75603_CR2","doi-asserted-by":"publisher","first-page":"552","DOI":"10.5530\/ijper.57.2.68","volume":"57","author":"G Subramanian","year":"2023","unstructured":"Subramanian, G., Chand, J., Jupudi, S. & Prudviraj, P. Synthesis and biological evaluation of the selected naphthalene substituted azetidinone derivatives targeting Parkinson\u2019s Disease. IJPER. 57, 552\u2013558. https:\/\/doi.org\/10.5530\/ijper.57.2.68 (2023).","journal-title":"IJPER"},{"key":"75603_CR3","doi-asserted-by":"publisher","first-page":"105799","DOI":"10.1016\/j.parkreldis.2023.105799","volume":"115","author":"CK Bhusal","year":"2023","unstructured":"Bhusal, C. K. et al. Unveiling Nature\u2019s potential: promising natural compounds in Parkinson\u2019s disease management. Parkinsonism Relat. Disord. 115, 105799. https:\/\/doi.org\/10.1016\/j.parkreldis.2023.105799 (2023).","journal-title":"Parkinsonism Relat. Disord"},{"key":"75603_CR4","doi-asserted-by":"publisher","first-page":"136","DOI":"10.2174\/1570159x18666201111110136","volume":"19","author":"S Singh","year":"2020","unstructured":"Singh, S. et al. Naturally inspired IMPHY000797s analogues for Alzheimer\u2019s Disease. Curr. Neuropharmacol. 19, 136\u2013151. https:\/\/doi.org\/10.2174\/1570159x18666201111110136 (2020).","journal-title":"Curr. Neuropharmacol."},{"key":"75603_CR5","doi-asserted-by":"publisher","first-page":"100095","DOI":"10.1016\/j.ejmcr.2022.100095","volume":"6","author":"S Pant","year":"2022","unstructured":"Pant, S., Kapri, A. & Nain, S. IMPHY000797 analogues for the management of neurodegenerative diseases. EJMCR. 6, 100095. https:\/\/doi.org\/10.1016\/j.ejmcr.2022.100095 (2022).","journal-title":"EJMCR"},{"key":"75603_CR6","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1021\/acs.jmedchem.1c00440","volume":"65","author":"DH Drewry","year":"2022","unstructured":"Drewry, D. H. et al. Identification of IMPHY000797-Based lead compounds for understudied kinases implicated in driving neurodegeneration. J. Med. Chem. 65, 1313\u20131328. https:\/\/doi.org\/10.1021\/acs.jmedchem.1c00440 (2022).","journal-title":"J. Med. Chem."},{"key":"75603_CR7","doi-asserted-by":"publisher","first-page":"114239","DOI":"10.1016\/j.biopha.2023.114239","volume":"159","author":"MA Javed","year":"2023","unstructured":"Javed, M. A. et al. Evaluation of IMPHY000797\/pyrrolidine-sertraline based hybrids as multitarget anti-alzheimer agents: In-vitro, in-vivo, and computational studies. Biomed. Pharmacother. 159, 114239. https:\/\/doi.org\/10.1016\/j.biopha.2023.114239 (2023).","journal-title":"Biomed. Pharmacother"},{"key":"75603_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40035-017-0099-z","volume":"6","author":"P Maiti","year":"2017","unstructured":"Maiti, P., Manna, J., Dunbar, G. L., Maiti, P. & Dunbar, G. L. Current understanding of the molecular mechanisms in Parkinson\u2019s disease: targets for potential treatments. Transl Neurodegener. 6, 1\u201335. https:\/\/doi.org\/10.1186\/s40035-017-0099-z (2017).","journal-title":"Transl Neurodegener"},{"key":"75603_CR9","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1055\/a-2231-1311","volume":"74","author":"G Subramanian","year":"2024","unstructured":"Subramanian, G., Prasad, K., Chand, J., Amarjith, T. K. & Shanish, A. A. In-silico, synthesis, characterization, and In-vitro studies on Benzylidene-based 2-chloroquinolin derivatives as free radical scavengers in Parkinson\u2019s Disease. Drug Res. 74, 67\u201376. https:\/\/doi.org\/10.1055\/a-2231-1311 (2024).","journal-title":"Drug Res."},{"key":"75603_CR10","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1007\/s11064-020-03058-3","volume":"45","author":"A Singh","year":"2020","unstructured":"Singh, A., Tripathi, P., Yadawa, A. K. & Singh, S. Promising polyphenols in Parkinson\u2019s disease therapeutics. Neurochem Res. 45, 1731\u20131745. https:\/\/doi.org\/10.1007\/s11064-020-03058-3 (2020).","journal-title":"Neurochem Res."},{"key":"75603_CR11","doi-asserted-by":"publisher","first-page":"3745","DOI":"10.1016\/j.csbj.2020.11.015","volume":"18","author":"C Wang","year":"2020","unstructured":"Wang, C., Chen, L., Zhang, M., Yang, Y. & Wong, G. PDmethDB: a curated Parkinson\u2019s disease associated methylation information database. Comput. Struct. Biotechnol. J. 18, 3745\u20133749. https:\/\/doi.org\/10.1016\/j.csbj.2020.11.015 (2020).","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"75603_CR12","doi-asserted-by":"publisher","first-page":"27","DOI":"10.33263\/BRIAC142.027","volume":"14","author":"MZ Baba","year":"2024","unstructured":"Baba, M. Z. et al. Investigation of Scutellaria baicalensis for potential neuroprotective effect on the treatment of Parkinson\u2019s Disease. Biointerface Res. Appl. Chem. 14, 27. https:\/\/doi.org\/10.33263\/BRIAC142.027 (2024).","journal-title":"Biointerface Res. Appl. Chem."},{"key":"75603_CR13","doi-asserted-by":"publisher","first-page":"288","DOI":"10.5501\/wjv.v10.i6.288","volume":"10","author":"QA Farooq","year":"2021","unstructured":"Farooq, Q. A., Shaukat, Z., Aiman, S. & Li, C. H. Protein-protein interactions: methods, databases, and applications in virus-host study. World J. Virol. 10, 288\u2013300. https:\/\/doi.org\/10.5501\/wjv.v10.i6.288 (2021).","journal-title":"World J. Virol."},{"key":"75603_CR14","doi-asserted-by":"publisher","first-page":"107526","DOI":"10.1016\/j.intimp.2021.107526","volume":"95","author":"MA Bonte","year":"2021","unstructured":"Bonte, M. A., El Idrissi, F., Gressier, B., Devos, D. & Belarbi, K. Protein network exploration prioritizes targets for modulating neuroinflammation in Parkinson\u2019s disease. Int. Immunopharmacol. 95, 107526. https:\/\/doi.org\/10.1016\/j.intimp.2021.107526 (2021).","journal-title":"Int. Immunopharmacol."},{"key":"75603_CR15","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto Encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"key":"75603_CR16","doi-asserted-by":"publisher","first-page":"48","DOI":"10.33263\/BRIAC142.048","volume":"14","author":"G Subramanian","year":"2024","unstructured":"Subramanian, G., Jupudi, S., Chand, J. & Baba, M. Z. Aryan, Network Pharmacology Approach and Molecular Docking Prediction to investigate the possible mechanism of Benzylidene Derivatives against Scavenging Reactive Oxygen Species via Sirtuin 3 in Parkinson\u2019s Disease. Biointerface Res. Appl. Chem. 14, 48. https:\/\/doi.org\/10.33263\/BRIAC142.048 (2024).","journal-title":"Biointerface Res. Appl. Chem."},{"key":"75603_CR17","unstructured":"Schr\u00f6dinger Release 2024-3: LigPrep, Schr\u00f6dinger, LLC, New York, NY, (2024)."},{"key":"75603_CR18","doi-asserted-by":"publisher","first-page":"2060080","DOI":"10.1002\/minf.202060080","volume":"40","author":"D Pirolli","year":"2021","unstructured":"Pirolli, D., Righino, B. & De Rosa, M. C. Targeting SARS-CoV-2 spike Protein\/ACE2 protein-protein interactions: a computational study. Mol. Inf. 40, 2060080. https:\/\/doi.org\/10.1002\/minf.202060080 (2021).","journal-title":"Mol. Inf."},{"issue":"3","key":"75603_CR19","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","volume":"27","author":"GM Sastry","year":"2013","unstructured":"Sastry, G. M., Adzhigirey, M., Day, T., Annabhimoju, R. & Sherman, W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J. Comput. Aid Mol. Des. 27 (3), 221\u2013234 (2013).","journal-title":"J. Comput. Aid Mol. Des."},{"key":"75603_CR20","doi-asserted-by":"crossref","unstructured":"Bowers, K. J. et al. Scalable algorithms for molecular dynamics simulations on commodity clusters, Proceedings of the ACM\/IEEE Conference on Supercomputing (SC06), Tampa, Florida, 11\u201317. (2006).","DOI":"10.1145\/1188455.1188544"},{"key":"75603_CR21","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.abst.2023.02.001","volume":"5","author":"KY Raheem","year":"2023","unstructured":"Raheem, K. Y. et al. Therapeutic capability of selected medicinal plants\u2019 bioactive constituents against the mutant ovarian TP53 gene; a computational approach. Adv. Biomark. Sci. Technol. 5, 8\u201332. https:\/\/doi.org\/10.1016\/j.abst.2023.02.001 (2023).","journal-title":"Adv. Biomark. Sci. Technol."},{"key":"75603_CR22","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","volume":"28","author":"M Kanehisa","year":"2019","unstructured":"Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947\u20131951 (2019).","journal-title":"Protein Sci."},{"key":"75603_CR23","doi-asserted-by":"publisher","first-page":"D587","DOI":"10.1093\/nar\/gkac963","volume":"51","author":"M Kanehisa","year":"2023","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 51, D587\u2013D592 (2023).","journal-title":"Nucleic Acids Res."},{"key":"75603_CR24","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13321-022-00626-3","volume":"14","author":"M Huang","year":"2022","unstructured":"Huang, M. et al. In silico prediction of UGT-mediated metabolism in drug-like molecules via graph neural network. J. Cheminform. 14, 46. https:\/\/doi.org\/10.1186\/s13321-022-00626-3 (2022).","journal-title":"J. Cheminform"},{"key":"75603_CR25","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1021\/acs.jcim.5b00019","volume":"55","author":"OA Tarasova","year":"2015","unstructured":"Tarasova, O. A. et al. QSAR modeling using large-scale databases: Case Study for HIV-1 reverse transcriptase inhibitors. J. Chem. Inf. Model. 55, 1388\u20131399. https:\/\/doi.org\/10.1021\/acs.jcim.5b00019 (2015).","journal-title":"J. Chem. Inf. Model."},{"key":"75603_CR26","doi-asserted-by":"publisher","first-page":"107881","DOI":"10.1016\/j.compbiolchem.2023.107881","volume":"105","author":"SD Ranade","year":"2023","unstructured":"Ranade, S. D. et al. Design, synthesis, molecular dynamics simulation, MM\/GBSA studies and kinesin spindle protein inhibitory evaluation of some 4-aminoquinoline hybrids. Comput. Biol. Chem. 105, 107881. https:\/\/doi.org\/10.1016\/j.compbiolchem.2023.107881 (2023).","journal-title":"Comput. Biol. Chem."},{"key":"75603_CR27","doi-asserted-by":"publisher","first-page":"319544","DOI":"10.3389\/fphar.2017.00941","volume":"8","author":"M Fumagalli","year":"2017","unstructured":"Fumagalli, M., Lecca, D., Abbracchio, M. P. & Ceruti, S. Pathophysiological role of purines and IMPHY000797s in neurodevelopment: unveiling new pharmacological approaches to congenital brain diseases. Front. Pharmacol. 8, 319544. https:\/\/doi.org\/10.3389\/fphar.2017.00941 (2017).","journal-title":"Front. Pharmacol."},{"key":"75603_CR28","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/2191-2858-2-34","volume":"2","author":"T Bano","year":"2012","unstructured":"Bano, T., Kumar, N. & Dudhe, R. Free radical scavenging properties of IMPHY000797 derivatives, Org. Med. Chem. Lett. 2, 34. https:\/\/doi.org\/10.1186\/2191-2858-2-34 (2012).","journal-title":"Med. Chem. Lett."},{"key":"75603_CR29","doi-asserted-by":"publisher","first-page":"3913","DOI":"10.3390\/molecules28093913","volume":"28","author":"M Myriagkou","year":"2023","unstructured":"Myriagkou, M. et al. Novel IMPHY000797 derivatives as antioxidant and Anticancer agents: design, synthesis and molecular modeling studies. Molecules. 28, 3913. https:\/\/doi.org\/10.3390\/molecules28093913 (2023).","journal-title":"Molecules"},{"key":"75603_CR30","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3389\/fnagi.2021.617588","volume":"13","author":"A Misrani","year":"2021","unstructured":"Misrani, A., Tabassum, S. & Yang, L. Mitochondrial dysfunction and oxidative stress in Alzheimer\u2019s Disease. Front. Aging Neurosci. 13, 57. https:\/\/doi.org\/10.3389\/fnagi.2021.617588 (2021).","journal-title":"Front. Aging Neurosci."},{"key":"75603_CR31","doi-asserted-by":"publisher","first-page":"552535","DOI":"10.3389\/fphys.2020.00694","volume":"11","author":"M Sharifi-Rad","year":"2020","unstructured":"Sharifi-Rad, M. et al. Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of Chronic diseases. Front. Physiol. 11, 552535. https:\/\/doi.org\/10.3389\/fphys.2020.00694 (2020).","journal-title":"Front. Physiol."},{"key":"75603_CR32","doi-asserted-by":"publisher","first-page":"13154","DOI":"10.1038\/s41598-021-92701-2","volume":"11","author":"P Quan","year":"2021","unstructured":"Quan, P. et al. Integrated network analysis identifying potential novel drug candidates and targets for Parkinson\u2019s disease. Sci. Rep. 11, 13154. https:\/\/doi.org\/10.1038\/s41598-021-92701-2 (2021).","journal-title":"Sci. Rep."},{"key":"75603_CR33","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.3390\/antiox10111649","volume":"10","author":"JA Parga","year":"2021","unstructured":"Parga, J. A., Rodriguez-Perez, A. I., Garcia-Garrote, M., Rodriguez-Pallares, J. & Labandeira-Garcia, J. L. Nrf2 activation and downstream effects: Focus on Parkinson\u2019s disease and brain angiotensin. Antioxidants. 10, 1649. https:\/\/doi.org\/10.3390\/antiox10111649 (2021).","journal-title":"Antioxidants"},{"key":"75603_CR34","doi-asserted-by":"publisher","unstructured":"Zhang, J. et al. Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target, Theranostics 10 8315\u20138342. (2020). https:\/\/doi.org\/10.7150\/thno.45922","DOI":"10.7150\/thno.45922"},{"key":"75603_CR35","doi-asserted-by":"publisher","first-page":"925350","DOI":"10.1155\/2014\/925350","volume":"2014","author":"Y Wang","year":"2014","unstructured":"Wang, Y., Zhou, Y. & Graves, D. T. FOXO transcription factors: their clinical significance and regulation. Biomed. Res. Int. 2014, 925350. https:\/\/doi.org\/10.1155\/2014\/925350 (2014).","journal-title":"Biomed. Res. Int."},{"key":"75603_CR36","doi-asserted-by":"publisher","first-page":"e13543","DOI":"10.14814\/phy2.13543","volume":"5","author":"DV Popov","year":"2017","unstructured":"Popov, D. V., Lysenko, E. A., Makhnovskii, P. A., Kurochkina, N. S. & Vinogradova, O. L. Regulation of PPARGC1A gene expression in trained and untrained human skeletal muscle. Physiol. Rep. 5, e13543. https:\/\/doi.org\/10.14814\/phy2.13543 (2017).","journal-title":"Physiol. Rep."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75603-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75603-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75603-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T14:04:06Z","timestamp":1728655446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75603-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,8]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["75603"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-75603-x","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,8]]},"assertion":[{"value":"23 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Gomathy Subramanian: Writing \u2013 review & editing, Writing \u2013 original draft, Visualization, Validation, Supervision, Software, Resources, Methodology, Investigation, Formal analysis, Conceptualization. Hannah Lalengzuali Fanai: Writing \u2013 review & editing, Writing \u2013 original draft, Supervision, Project administration, Investigation, Funding acquisition, Conceptualization. Jagdish Chand: Conceptualization, Data curation, Formal analysis, Methodology, Supervision, Validation, Writing\u2013 original draft, Writing\u2013 review & editing. Sheikh F. Ahmad: Methodology, Validation, Writing\u2013 original draft, Writing\u2013 review & editing. Sabry M. Attia: Methodology, Validation, Writing\u2013 original draft, Writing\u2013 review & editing. Talha Bin Emran: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing\u2013 original draft, Writing\u2013 review & editing.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"CRediT authorship contribution statement"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of competing interest"}},{"value":"The Supplementary file has been provided in the form of .csv files.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of competing interest"}}],"article-number":"23414"}}