{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:05:57Z","timestamp":1770678357617,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Targeting the vascular endothelial growth factor (VEGF) pathway is crucial for antiangiogenesis therapy in treating cancers and diseases with abnormal blood vessel growth. Human umbilical vein endothelial cells (HUVECs) activated by VEGF are widely used for exploring the impact of antiangiogenic agents on cellular functions. In this study, seven quinolinone derivatives were successfully synthesized and structurally confirmed through\n                    <jats:sup>1<\/jats:sup>\n                    H,\n                    <jats:sup>13<\/jats:sup>\n                    C NMR, and HRMS spectra. Compounds\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>5<\/jats:bold>\n                    exhibited significant inhibition of VEGF\u2010induced HUVEC proliferation, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 84.8 and 58.1\u2009\u03bcM for 48\u2009h. Compounds\n                    <jats:bold>3<\/jats:bold>\n                    \u2012\n                    <jats:bold>6<\/jats:bold>\n                    effectively suppressed VEGF\u2010induced HUVEC migration and invasion, demonstrating potent inhibitory effects in the Matrigel tube formation assay. Compounds\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>5<\/jats:bold>\n                    directly bind to vascular endothelial growth factor receptor 2 (VEGFR2), thereby inhibiting VEGFR2\u2010mediated downstream angiogenic signaling pathways (PI3K\/Akt, ERK1\/2\/p38 MAPK, and FAK). Cell\u2010cycle analysis revealed that compounds\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>5<\/jats:bold>\n                    induced substantial G\n                    <jats:sub>2<\/jats:sub>\n                    \/M phase arrest in HUVECs, accompanied by increased p53 phosphorylation and upregulation of p21\n                    <jats:sup>cip1<\/jats:sup>\n                    expression. Compounds\n                    <jats:bold>3<\/jats:bold>\n                    \u2012\n                    <jats:bold>6<\/jats:bold>\n                    also induced apoptosis in HUVECs, as evidenced by nuclear condensation, DNA laddering, and increased Annexin V\/PI staining. Western blot analysis showed that compounds\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>5<\/jats:bold>\n                    significantly increased the levels of apoptosis\u2010related proteins, particularly cleaved caspase\u20103 and PARP. Through in vivo experiments utilizing the chicken embryo chorioallantoic membrane (CAM) assay, a marked decline in newly formed microvessels was observed posttreatment with both compounds. These results suggest that compounds\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>5<\/jats:bold>\n                    show promise as antiangiogenic agents, warranting further investigation into their therapeutic efficacy in conditions characterized by abnormal angiogenesis.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70040","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:36:23Z","timestamp":1751348183000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quinolinone Derivatives Suppress Angiogenesis in Human Umbilical Vein Endothelial Cells by Blocking the VEGF\u2010Induced VEGFR2 Signaling Pathway"],"prefix":"10.1002","volume":"358","author":[{"given":"Xiaoxi","family":"Lin","sequence":"first","affiliation":[{"name":"Clinical Research Center Affiliated Hospital of Guangdong Medical University Zhanjiang Guangdong China"},{"name":"Department of Respiratory Medicine Affiliated Hospital of Guangdong Medical University Zhanjiang Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bonian","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Research Center Affiliated Hospital of Guangdong Medical University Zhanjiang Guangdong China"},{"name":"Department of Respiratory Medicine Affiliated Hospital of Guangdong Medical University Zhanjiang Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Clinical Research Center Affiliated Hospital of Guangdong Medical University Zhanjiang Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Bioengineering Chongqing University of Technology Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiming","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Affiliated Hospital of Guangdong Medical University Zhanjiang Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7737-4575","authenticated-orcid":false,"given":"Ao","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Research Center Affiliated Hospital of Guangdong Medical University Zhanjiang Guangdong China"},{"name":"Department of Anesthesiology Affiliated Hospital of Guangdong Medical University Zhanjiang Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.021"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370214533883"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2013.10.001"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.271"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-012-9394-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073765"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.842960"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.153031"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(03)00424-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7730"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2016.05.014"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3746\/pnf.2017.22.4.320"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1156-5"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2403"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2019.04.017"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2013.42"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2013.05.033"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005090"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2741\/4378"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.02.026"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-012-9270-4"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00803-4"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.791860"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126725"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14022334"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.273"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.3c01974"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.0c00172"},{"key":"e_1_2_8_30_1","unstructured":"Y.Zheng X.Xu R.Wang et al. \u201cA Side\u2010Chain\u2010Substituted Alkyl Quinolone Compound Its Preparation Method as Well as Its Pharmaceutical Composition and Uses \u201d ZL201310064184.3 (2013) [Patent in Chinese]."},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1260198"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo701384n"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol100954x"},{"key":"e_1_2_8_34_1","first-page":"8","volume-title":"Using AutoDock for Ligand\u2010Receptor Docking","author":"Morris G. 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