Targeting matrix metalloproteinase-9 (MMP9) in prostate cancer: a computational study on natural product-derived novel potential inhibitors
Abstract Background Prostate cancer is one of the prime causes of death in men worldwide; the number of patients has increased every year despite significant efforts and outlay in the research of prostate cancer. Identifying new natural targets for effective prostate cancer treatment remains a major...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-07-01
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| Series: | Future Journal of Pharmaceutical Sciences |
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| Online Access: | https://doi.org/10.1186/s43094-025-00838-y |
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| author | Vipendra Kumar Singh Naina Rajak Prashant Kumar Gupta Arun Kumar Mahapatra Ankit Kumar Singh Rajanish Giri Neha Garg |
| author_facet | Vipendra Kumar Singh Naina Rajak Prashant Kumar Gupta Arun Kumar Mahapatra Ankit Kumar Singh Rajanish Giri Neha Garg |
| author_sort | Vipendra Kumar Singh |
| collection | DOAJ |
| description | Abstract Background Prostate cancer is one of the prime causes of death in men worldwide; the number of patients has increased every year despite significant efforts and outlay in the research of prostate cancer. Identifying new natural targets for effective prostate cancer treatment remains a major challenge in contemporary research. Natural products may provide an excellent source for drug development against prostate cancer. The DisGeNET and GeneCards databases were used to identify the anti-cancer proteins involved in prostate cancer. Furthermore, the Search Tool for the Retrieval of Interacting Genes/Proteins database was utilized to identify the hub genes. The hub genes were processed using the Gene Expression Profiling Interactive Analysis database to get the difference in transcriptional expression between prostate cancer tissue and normal tissue. The 3D structures of selected targets were acquired from the protein data bank, and molecular docking was carried out. Higher expression of hub genes such as matrix metalloproteinase-9 (MMP9) was significantly linked with overall and progression-free survival in prostate cancer patients. Finally, the 200 ns molecular dynamics (MD) simulation was performed to check the stable interaction of compounds with the MMP9. Results Co-expression investigation demonstrates that identified hub genes play a crucial role in prostate cancer and are controlled by many miRNAs. Molecular docking studies demonstrated that D-Galacturonic acid, glycerides, C14-18 showed better docking scores (− 8.0) with targeted MMP9 protein. MD simulation showed a stable interaction of bioactive compounds, such as D-Galacturonic acid, glycerides, C14-18 with the MMP9 protein. Conclusions The present study highlights that bioactive compounds could be an effective anti-cancer drug against MMP9 in prostate cancer and can be further validated using different preclinical studies. Graphical abstract |
| format | Article |
| id | doaj-art-defce076d4a14c628972500f1f823cdd |
| institution | Kabale University |
| issn | 2314-7253 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Future Journal of Pharmaceutical Sciences |
| spelling | doaj-art-defce076d4a14c628972500f1f823cdd2025-08-20T03:37:28ZengSpringerOpenFuture Journal of Pharmaceutical Sciences2314-72532025-07-0111112210.1186/s43094-025-00838-yTargeting matrix metalloproteinase-9 (MMP9) in prostate cancer: a computational study on natural product-derived novel potential inhibitorsVipendra Kumar Singh0Naina Rajak1Prashant Kumar Gupta2Arun Kumar Mahapatra3Ankit Kumar Singh4Rajanish Giri5Neha Garg6School of Biosciences and Bioengineering, Indian Institute of Technology MandiDepartment of Medicinal Chemistry, Institute of Medical Sciences, Faculty of Ayurveda, Banaras Hindu UniversityAyurinformatics Laboratory, All India Institute of AyurvedaAyurinformatics Laboratory, All India Institute of AyurvedaUniversity Department of Botany, Lalit Narayan Mithila UniversitySchool of Biosciences and Bioengineering, Indian Institute of Technology MandiDepartment of Medicinal Chemistry, Institute of Medical Sciences, Faculty of Ayurveda, Banaras Hindu UniversityAbstract Background Prostate cancer is one of the prime causes of death in men worldwide; the number of patients has increased every year despite significant efforts and outlay in the research of prostate cancer. Identifying new natural targets for effective prostate cancer treatment remains a major challenge in contemporary research. Natural products may provide an excellent source for drug development against prostate cancer. The DisGeNET and GeneCards databases were used to identify the anti-cancer proteins involved in prostate cancer. Furthermore, the Search Tool for the Retrieval of Interacting Genes/Proteins database was utilized to identify the hub genes. The hub genes were processed using the Gene Expression Profiling Interactive Analysis database to get the difference in transcriptional expression between prostate cancer tissue and normal tissue. The 3D structures of selected targets were acquired from the protein data bank, and molecular docking was carried out. Higher expression of hub genes such as matrix metalloproteinase-9 (MMP9) was significantly linked with overall and progression-free survival in prostate cancer patients. Finally, the 200 ns molecular dynamics (MD) simulation was performed to check the stable interaction of compounds with the MMP9. Results Co-expression investigation demonstrates that identified hub genes play a crucial role in prostate cancer and are controlled by many miRNAs. Molecular docking studies demonstrated that D-Galacturonic acid, glycerides, C14-18 showed better docking scores (− 8.0) with targeted MMP9 protein. MD simulation showed a stable interaction of bioactive compounds, such as D-Galacturonic acid, glycerides, C14-18 with the MMP9 protein. Conclusions The present study highlights that bioactive compounds could be an effective anti-cancer drug against MMP9 in prostate cancer and can be further validated using different preclinical studies. Graphical abstracthttps://doi.org/10.1186/s43094-025-00838-yGEPIAHibiscus esculentus (L.)Molecular dockingMolecular dynamics (MD) simulationNatural compoundsNetwork pharmacology |
| spellingShingle | Vipendra Kumar Singh Naina Rajak Prashant Kumar Gupta Arun Kumar Mahapatra Ankit Kumar Singh Rajanish Giri Neha Garg Targeting matrix metalloproteinase-9 (MMP9) in prostate cancer: a computational study on natural product-derived novel potential inhibitors Future Journal of Pharmaceutical Sciences GEPIA Hibiscus esculentus (L.) Molecular docking Molecular dynamics (MD) simulation Natural compounds Network pharmacology |
| title | Targeting matrix metalloproteinase-9 (MMP9) in prostate cancer: a computational study on natural product-derived novel potential inhibitors |
| title_full | Targeting matrix metalloproteinase-9 (MMP9) in prostate cancer: a computational study on natural product-derived novel potential inhibitors |
| title_fullStr | Targeting matrix metalloproteinase-9 (MMP9) in prostate cancer: a computational study on natural product-derived novel potential inhibitors |
| title_full_unstemmed | Targeting matrix metalloproteinase-9 (MMP9) in prostate cancer: a computational study on natural product-derived novel potential inhibitors |
| title_short | Targeting matrix metalloproteinase-9 (MMP9) in prostate cancer: a computational study on natural product-derived novel potential inhibitors |
| title_sort | targeting matrix metalloproteinase 9 mmp9 in prostate cancer a computational study on natural product derived novel potential inhibitors |
| topic | GEPIA Hibiscus esculentus (L.) Molecular docking Molecular dynamics (MD) simulation Natural compounds Network pharmacology |
| url | https://doi.org/10.1186/s43094-025-00838-y |
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