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Here, we report a comprehensive analysis of new pyrazolone derivatives, prepared according to a clear-cut, uncomplicated procedure. The pyrazolone derivatives were thoroughly characterized using various methods, such as elemental analysis, NMR, and FT-IR. The molecular docking interactions between the new pyrazolone derivatives and YAP\/TEAD target protein observed that compound <jats:bold>4<\/jats:bold> had the top-ranked binding energy towards YAP\/TEAD with a value equal to \u2212\u20099.670 kcal\/mol and this theoretically proves its inhibitory efficacy against YAP\/TEAD Hippo signaling pathway. Besides, compound <jats:bold>4<\/jats:bold> showed the best IC<jats:sub>50<\/jats:sub> against HCT-116, HepG-2, and MCF-7\u00a0(<jats:italic>in-vitro<\/jats:italic>) with IC<jats:sub>50<\/jats:sub> 7.67\u2009\u00b1\u20090.5, 5.85\u2009\u00b1\u20090.4, and 6.97\u2009\u00b1\u20090.5 \u03bcM, respectively which confirmed our results towards suppressing YAP\/TEAD protein (<jats:italic>in-silico<\/jats:italic>) compared with the IC<jats:sub>50<\/jats:sub> of Sorafenib (SOR) reference chemotherapeutic drug 5.47\u2009\u00b1\u20090.3, 9.18\u2009\u00b1\u20090.6 and 7.26\u2009\u00b1\u20090.3 \u03bcM, respectively. Also, compound <jats:bold>4<\/jats:bold> showed no cytotoxic effects against human lung fibroblast normal cell line (WI-38) and its pharmacokinetics were elucidated theoretically using ADMET compared with SOR which observed highly toxic effects on normal cells with IC<jats:sub>50<\/jats:sub> equal to 20.27\u2009\u00b1\u20090.45 \u03bcM. Additionally, compound <jats:bold>4<\/jats:bold> clarified a powerful antioxidant scavenging activity against DPPH free radicals (<jats:italic>in-vitro<\/jats:italic>). Conclusively, newly synthesized pyrazolone derivative\u00a0<jats:bold>4<\/jats:bold> could be used as anticancer candidate via inhibiting the YAP\/TEAD mediated Hippo signaling pathway.<\/jats:p>","DOI":"10.1038\/s41598-024-79992-x","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T12:05:58Z","timestamp":1732190758000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Discovering the inhibition of YAP\/TEAD Hippo signaling pathway via new pyrazolone derivatives: synthesis, molecular docking and biological investigations"],"prefix":"10.1038","volume":"14","author":[{"given":"Ahmed A.","family":"Noser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9108-6932","authenticated-orcid":false,"given":"Maha M.","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed H.","family":"Baren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel I.","family":"Selim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esraa M.","family":"ElSafty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"79992_CR1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1097\/CM9.0000000000001474","volume":"134","author":"W Cao","year":"2020","unstructured":"Cao, W., Chen, H. 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