Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study
<h3>Background</h3><p dir="ltr">Hypoxia plays a key role in cancer progression, mainly by stabilizing and activating hypoxia-inducible factor-1 (HIF-1). For HIF-1 to function under low oxygen conditions, it must interact with the transcriptional coactivator p300, a critic...
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2025
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| _version_ | 1864513537445986304 |
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| author | Muhammad Suleman (3829027) |
| author2 | Abrar Mohammad Sayaf (11644294) Sohail Aftab (22443284) Mohammed Alissa (18607830) Abdullah Alghamdi (14375904) Suad A. Alghamdi (21998691) Mohammed A. Alshehri (18696547) Kar Kheng Yeoh (1933633) Sergio Crovella (20921252) Abdullah Shaito (20545181) |
| author2_role | author author author author author author author author author |
| author_facet | Muhammad Suleman (3829027) Abrar Mohammad Sayaf (11644294) Sohail Aftab (22443284) Mohammed Alissa (18607830) Abdullah Alghamdi (14375904) Suad A. Alghamdi (21998691) Mohammed A. Alshehri (18696547) Kar Kheng Yeoh (1933633) Sergio Crovella (20921252) Abdullah Shaito (20545181) |
| author_role | author |
| dc.creator.none.fl_str_mv | Muhammad Suleman (3829027) Abrar Mohammad Sayaf (11644294) Sohail Aftab (22443284) Mohammed Alissa (18607830) Abdullah Alghamdi (14375904) Suad A. Alghamdi (21998691) Mohammed A. Alshehri (18696547) Kar Kheng Yeoh (1933633) Sergio Crovella (20921252) Abdullah Shaito (20545181) |
| dc.date.none.fl_str_mv | 2025-04-21T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/ph18040602 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Medicinal_Phytocompounds_as_Potential_Inhibitors_of_p300-HIF1_Interaction_A_Structure-Based_Screening_and_Molecular_Dynamics_Simulation_Study/30363661 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Bioinformatics and computational biology Biomedical and clinical sciences Oncology and carcinogenesis Pharmacology and pharmaceutical sciences Chemical sciences Medicinal and biomolecular chemistry Health sciences Traditional, complementary and integrative medicine p300 HIF-1 hypoxia phytocompounds drug screening MD simulation binding free energy |
| dc.title.none.fl_str_mv | Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">Hypoxia plays a key role in cancer progression, mainly by stabilizing and activating hypoxia-inducible factor-1 (HIF-1). For HIF-1 to function under low oxygen conditions, it must interact with the transcriptional coactivator p300, a critical step for promoting cancer cell survival and adaptation in hypoxic environments.</p><h3>Methods</h3><p dir="ltr">Consequently, we used drug design and molecular simulation techniques to screen phytochemical databases, including traditional Chinese and African medicine sources, for compounds that could disrupt the p300/HIF-1 interaction.</p><h3>Results</h3><p dir="ltr">In this study, we identified potential compounds with high docking scores such as EA-176920 (−8.719), EA-46881231 (−8.642), SA-31161 (−9.580), SA-5280863 (−8.179), NE-5280362 (−10.287), NE-72276 (−9.017), NA-11210533 (−10.366), NA-11336960 (−7.818), TCM-5281792 (−12.648), and TCM-6441280 (−9.470 kcal/mol) as lead compounds. Furthermore, the compound with the highest docking score from each database (EA-176920, SA-31161, NE-5280362, NA-11210533, and TCM-5281792) was subjected to further analysis. The stable binding affinity of these compounds with p300 was confirmed by Post-simulation binding free energy (−22.0020 kcal/mol, −25.4499 kcal/mol, −32.4530 kcal/mol, −33.9918 kcal/mol, and −57.7755 kcal/mol, respectively) and KD analysis. Moreover, the selected compounds followed the Lipinski rules with favorable ADMET properties like efficient intestinal absorption, high water solubility, and no toxicity. </p><h3>Conclusions</h3><p dir="ltr">Our findings highlight the potential of natural compounds to target key protein–protein interactions in cancer and lay the groundwork for future in vitro and in vivo studies to explore their therapeutic potential. Specifically, disrupting the p300/HIF-1 interaction could interfere with hypoxia-driven pathways that promote tumor growth, angiogenesis, and metastasis, offering a promising strategy to suppress cancer progression at the molecular level.</p><h2>Other Information</h2><p dir="ltr">Published in: Pharmaceuticals<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://doi.org/10.3390/ph18040602" target="_blank">https://doi.org/10.3390/ph18040602</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_cfa75be691f215178169f2dc89b9e028 |
| identifier_str_mv | 10.3390/ph18040602 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/30363661 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation StudyMuhammad Suleman (3829027)Abrar Mohammad Sayaf (11644294)Sohail Aftab (22443284)Mohammed Alissa (18607830)Abdullah Alghamdi (14375904)Suad A. Alghamdi (21998691)Mohammed A. Alshehri (18696547)Kar Kheng Yeoh (1933633)Sergio Crovella (20921252)Abdullah Shaito (20545181)Biological sciencesBiochemistry and cell biologyBioinformatics and computational biologyBiomedical and clinical sciencesOncology and carcinogenesisPharmacology and pharmaceutical sciencesChemical sciencesMedicinal and biomolecular chemistryHealth sciencesTraditional, complementary and integrative medicinep300HIF-1hypoxiaphytocompoundsdrug screeningMD simulationbinding free energy<h3>Background</h3><p dir="ltr">Hypoxia plays a key role in cancer progression, mainly by stabilizing and activating hypoxia-inducible factor-1 (HIF-1). For HIF-1 to function under low oxygen conditions, it must interact with the transcriptional coactivator p300, a critical step for promoting cancer cell survival and adaptation in hypoxic environments.</p><h3>Methods</h3><p dir="ltr">Consequently, we used drug design and molecular simulation techniques to screen phytochemical databases, including traditional Chinese and African medicine sources, for compounds that could disrupt the p300/HIF-1 interaction.</p><h3>Results</h3><p dir="ltr">In this study, we identified potential compounds with high docking scores such as EA-176920 (−8.719), EA-46881231 (−8.642), SA-31161 (−9.580), SA-5280863 (−8.179), NE-5280362 (−10.287), NE-72276 (−9.017), NA-11210533 (−10.366), NA-11336960 (−7.818), TCM-5281792 (−12.648), and TCM-6441280 (−9.470 kcal/mol) as lead compounds. Furthermore, the compound with the highest docking score from each database (EA-176920, SA-31161, NE-5280362, NA-11210533, and TCM-5281792) was subjected to further analysis. The stable binding affinity of these compounds with p300 was confirmed by Post-simulation binding free energy (−22.0020 kcal/mol, −25.4499 kcal/mol, −32.4530 kcal/mol, −33.9918 kcal/mol, and −57.7755 kcal/mol, respectively) and KD analysis. Moreover, the selected compounds followed the Lipinski rules with favorable ADMET properties like efficient intestinal absorption, high water solubility, and no toxicity. </p><h3>Conclusions</h3><p dir="ltr">Our findings highlight the potential of natural compounds to target key protein–protein interactions in cancer and lay the groundwork for future in vitro and in vivo studies to explore their therapeutic potential. Specifically, disrupting the p300/HIF-1 interaction could interfere with hypoxia-driven pathways that promote tumor growth, angiogenesis, and metastasis, offering a promising strategy to suppress cancer progression at the molecular level.</p><h2>Other Information</h2><p dir="ltr">Published in: Pharmaceuticals<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://doi.org/10.3390/ph18040602" target="_blank">https://doi.org/10.3390/ph18040602</a></p>2025-04-21T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ph18040602https://figshare.com/articles/journal_contribution/Medicinal_Phytocompounds_as_Potential_Inhibitors_of_p300-HIF1_Interaction_A_Structure-Based_Screening_and_Molecular_Dynamics_Simulation_Study/30363661CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/303636612025-04-21T03:00:00Z |
| spellingShingle | Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study Muhammad Suleman (3829027) Biological sciences Biochemistry and cell biology Bioinformatics and computational biology Biomedical and clinical sciences Oncology and carcinogenesis Pharmacology and pharmaceutical sciences Chemical sciences Medicinal and biomolecular chemistry Health sciences Traditional, complementary and integrative medicine p300 HIF-1 hypoxia phytocompounds drug screening MD simulation binding free energy |
| status_str | publishedVersion |
| title | Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study |
| title_full | Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study |
| title_fullStr | Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study |
| title_full_unstemmed | Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study |
| title_short | Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study |
| title_sort | Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study |
| topic | Biological sciences Biochemistry and cell biology Bioinformatics and computational biology Biomedical and clinical sciences Oncology and carcinogenesis Pharmacology and pharmaceutical sciences Chemical sciences Medicinal and biomolecular chemistry Health sciences Traditional, complementary and integrative medicine p300 HIF-1 hypoxia phytocompounds drug screening MD simulation binding free energy |