{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:49:55Z","timestamp":1791496195835,"version":"4.3.4"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>This study aimed to design, synthesize, and evaluate novel morpholine-substituted phenoxyacetohydrazide derivatives as potential anti-inflammatory and anti-angiogenic agents. The compounds were synthesized and characterized by FTIR, NMR, mass spectrometry, and elemental analysis. In silico molecular docking revealed that compound <jats:bold>6e<\/jats:bold> exhibited strong binding affinities toward vascular endothelial growth factor (VEGF), cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2), with docking scores of \u201313.1622, \u201312.5301, and \u201312.6705 (kcal\/mol) respectively. The in vitro anti-inflammatory activity, assessed via the human red blood cell (HRBC) membrane stabilization assay, showed that compound 6e achieved an IC\u2085\u2080 value of 155 \u03bcg\/mL, indicating potent efficacy. Additionally, <jats:bold>6e<\/jats:bold> demonstrated significant anti-angiogenic activity in both in vivo and ex vivo chick chorioallantoic membrane (CAM) models, inhibiting VEGF-induced angiogenesis in a dose-dependent manner and markedly reducing microvessel density and vessel length. In a rat model of alkali-induced corneal neovascularization, compound <jats:bold>6e<\/jats:bold> substantially suppressed neovascular growth. Moreover, in the carrageenan-induced paw edema model, it effectively reduced edema, neutrophil infiltration, and myeloperoxidase activity. Collectively, these findings position compound <jats:bold>6e<\/jats:bold> as a promising dual-action therapeutic candidate for treating chronic inflammation and pathological angiogenesis. This study underscores the potential of systematically designed phenoxyacetohydrazide scaffolds as multi-targeted therapeutic agents.<\/jats:p>","DOI":"10.1371\/journal.pone.0330731","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:44:17Z","timestamp":1758908657000},"page":"e0330731","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synthesis of novel phenoxyacetohydrazide compounds and evaluation therapeutic potential exhibit as anti-inflammatory and anti-angiogenic"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1086-7292","authenticated-orcid":true,"given":"Yasser Hussein Issa","family":"Mohammed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0723-5622","authenticated-orcid":true,"given":"Ahmed 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