{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:10:03Z","timestamp":1783926603874,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":192,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["114-2113-M-032-003"],"award-info":[{"award-number":["114-2113-M-032-003"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Toxicology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Angiogenesis is crucial for tissue repair and the treatment of ischemic diseases, yet effective small\u2010molecule proangiogenic agents are lacking in clinical practice. Chalcone\u2010based compounds are of interest due to their diverse biological activities. This study aimed to synthesize and evaluate the proangiogenic potential of a series of novel chalcone derivatives and to elucidate their structure\u2013activity relationship (SAR) using computational chemistry. We synthesized and tested six chalcone derivatives (1a\u20131f), with compound (\n                    <jats:italic>E<\/jats:italic>\n                    )\u20101\u2010(3,4\u2010dimethoxyphenyl)\u20103\u2010(3\u2010hydroxy\u20104\u2010methoxyphenyl)prop\u20102\u2010en\u20101\u2010one (1c) exhibiting the highest activity. In the zebrafish model, treatment with 1c significantly increased the formation of branch points and vessel outgrowth in the subintestinal vein (SIV) (number of branch points: 1c group 2.28\u2009\u00b1\u20090.19, control group 0.79\u2009\u00b1\u20090.17;\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001). Using Tg(\n                    <jats:italic>fli1:egfp<\/jats:italic>\n                    ) transgenic zebrafish, we observed that 1c dramatically promoted the remodeling of the caudal vein plexus (CVP), leading to a significant increase in the number of intercapillary spaces (1c group 16.3\u2009\u00b1\u20091.9, mock group 11.6\u2009\u00b1\u20092). Mechanistically, real\u2010time polymerase chain reaction (RT\u2010PCR) results showed that 1c treatment upregulated the expression of key angiogenic genes cadherin 5 and neuropilin 1a, while downregulating the expression of fms\u2010related receptor tyrosine kinase 1. Furthermore, the chick embryo chorioallantoic membrane (CAM) assay confirmed that 1c effectively induced vascular network formation. Computational chemistry analyses (DFT, MESP, and FMO) were highly consistent with the biological activity. 1c possessed the highest electrophilicity index (\n                    <jats:italic>\u03c9<\/jats:italic>\n                    ), chemical potential (\n                    <jats:italic>\u03bc<\/jats:italic>\n                    ), and electron transfer capability (\u0394\n                    <jats:italic>N<\/jats:italic>\n                    ), as well as the strongest electrophilic site (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>s<\/jats:italic>\n                      ,max\n                    <\/jats:sub>\n                    ), which explains its superior biological activity. This study confirms the potent proangiogenic activity of chalcone derivative 1c, providing a promising lead compound for the development of novel small\u2010molecule therapeutics targeting vascular dysfunction diseases.\n                  <\/jats:p>","DOI":"10.1155\/jt\/6939974","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:41:14Z","timestamp":1783924874000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phenotype\u2010Driven Discovery of Pro\u2010Revascularization Chalcone Derivatives Using Zebrafish and CAM Models"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4436-7464","authenticated-orcid":false,"given":"Yau-Hung","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6636-3934","authenticated-orcid":false,"given":"Biswajit","family":"Mohanty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7653-8873","authenticated-orcid":false,"given":"Tao-Sheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Fen","family":"Tung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Chung","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3745-9187","authenticated-orcid":false,"given":"Parthapratim","family":"Munshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1554-0176","authenticated-orcid":false,"given":"Ching-Yuh","family":"Chern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2009.41.12.103"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semvascsurg.2014.10.001"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2016.09.003"},{"key":"e_1_2_9_4_2","first-page":"687","article-title":"Tumor Angiogenesis and Anti-Angiogenic Gene Therapy for Cancer","volume":"16","author":"Li T.","year":"2018","journal-title":"Oncology Letters"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj0153"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2022.104339"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2020.102017"},{"key":"e_1_2_9_8_2","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2407-14-614","article-title":"Angiopoietin-1 Mimetic, Reduces Acute Skin Ionizing Radiation Damage in a Preclinical Mouse Model","volume":"14","author":"Korpela E.","year":"2014","journal-title":"BMC Cancer"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.00854.x"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076844"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.4103\/tcmj.tcmj_59_24"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102288"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2020.109315"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-01292-5"},{"key":"e_1_2_9_15_2","article-title":"Synthesis, Anticancer Assessment, and Molecular Docking of Novel Chalcone-Thienopyrimidine Derivatives in HepG2 and MCF-7 Cell Lines","author":"Safwat G. 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