{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:19:08Z","timestamp":1793755148574,"version":"4.6.1"},"reference-count":86,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Qatar University","award":["QUPD CAS-23-24491"],"award-info":[{"award-number":["QUPD CAS-23-24491"]}]},{"name":"Qatar University","award":["PSAU\/2025\/R\/1446"],"award-info":[{"award-number":["PSAU\/2025\/R\/1446"]}]},{"name":"Prince Sattam bin Abdulaziz University","award":["QUPD CAS-23-24491"],"award-info":[{"award-number":["QUPD CAS-23-24491"]}]},{"name":"Prince Sattam bin Abdulaziz University","award":["PSAU\/2025\/R\/1446"],"award-info":[{"award-number":["PSAU\/2025\/R\/1446"]}]},{"name":"Qatar University Biomedical Research Center (BRC)","award":["QUPD CAS-23-24491"],"award-info":[{"award-number":["QUPD CAS-23-24491"]}]},{"name":"Qatar University Biomedical Research Center (BRC)","award":["PSAU\/2025\/R\/1446"],"award-info":[{"award-number":["PSAU\/2025\/R\/1446"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: 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. Methods: 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. Results: In this study, we identified potential compounds with high docking scores such as EA-176920 (\u22128.719), EA-46881231 (\u22128.642), SA-31161 (\u22129.580), SA-5280863 (\u22128.179), NE-5280362 (\u221210.287), NE-72276 (\u22129.017), NA-11210533 (\u221210.366), NA-11336960 (\u22127.818), TCM-5281792 (\u221212.648), and TCM-6441280 (\u22129.470 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 (\u221222.0020 kcal\/mol, \u221225.4499 kcal\/mol, \u221232.4530 kcal\/mol, \u221233.9918 kcal\/mol, and \u221257.7755 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. Conclusions: Our findings highlight the potential of natural compounds to target key protein\u2013protein 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.<\/jats:p>","DOI":"10.3390\/ph18040602","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T20:42:00Z","timestamp":1745268120000},"page":"602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1\u03b1 Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study"],"prefix":"10.3390","volume":"18","author":[{"given":"Muhammad","family":"Suleman","sequence":"first","affiliation":[{"name":"Laboratory of Animal Research Center (LARC), Qatar University, Doha P.O. Box 2713, Qatar"},{"name":"Center for Biotechnology and Microbiology, University of Swat, Swat 19200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrar Mohammad","family":"Sayaf","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, Universiti Sains Malaysia, Gelugor 10050, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohail","family":"Aftab","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Microbiology, University of Swat, Swat 19200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4045-0810","authenticated-orcid":false,"given":"Mohammed","family":"Alissa","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6635-3102","authenticated-orcid":false,"given":"Abdullah","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8325-5994","authenticated-orcid":false,"given":"Suad A.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2139-5904","authenticated-orcid":false,"given":"Mohammed A.","family":"Alshehri","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kar Kheng","family":"Yeoh","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, Universiti Sains Malaysia, Gelugor 10050, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8493-1168","authenticated-orcid":false,"given":"Sergio","family":"Crovella","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Research Center (LARC), Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-7962","authenticated-orcid":false,"given":"Abdullah A.","family":"Shaito","sequence":"additional","affiliation":[{"name":"Biomedical Research Center (BRC), Department of Biomedical Sciences at College of Health Sciences, and College of Medicine, QU Health, Qatar University, Doha P.O. 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