{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:16:28Z","timestamp":1777860988633,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,4,28]]},"abstract":"<jats:p>\n                    Inhibition of the VEGF\/VEGFR\u20102 pathway is a validated strategy to suppress tumor angiogenesis and progression; however, long\u2010term use of several VEGFR\u20102 tyrosine kinase inhibitors is limited by resistance and systemic toxicity. Here, a series of novel indolinone\u2013matrine hybrids were designed and synthesized via a molecular hybridization strategy. The antiproliferative activities were evaluated against human hepatocellular carcinoma (HCC) cell lines (HepG\u20102, HuH7, and MHCC97H). Among them, J9 showed the most potent activity with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 5.81, 2.14, and 3.03\u2009\u03bcM, respectively, and relatively low cytotoxicity toward HEK\u2010293 cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200927.90\u2009\u03bcM) and HL7702 cells (IC50\u2009=\u200952.23\u2009\u03bcM). In HuH7 cells, J9 significantly inhibited colony formation and migration, induced G1\u2010phase arrest, and promoted apoptosis in a dose\u2010dependent manner. Western blot analysis indicated that J9 treatment was associated with downregulation of VEGFR\u20102 and activation of caspase\u2010dependent apoptosis (increased cleaved caspase\u20103 and cleaved PARP). Moreover, J9 inhibited VEGFR\u20102 kinase in vitro (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u2009253.51\u2009\u00b1\u20091.21\u2009nM), and docking\/MD simulations suggested stable binding within the VEGFR\u20102 ATP\u2010binding pocket. Collectively, J9 represents a promising matrine\u2010derived antitumor candidate with potential VEGFR\u20102\u2010targeting activity.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70283","type":"journal-article","created":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T03:55:44Z","timestamp":1777175744000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Biological Evaluation of Indolin\u20102\u2010One\u2013Matrine Derivatives as Potential VEGFR\u20102\u2010Targeting Agents for Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"21","author":[{"given":"Ziyi","family":"Wang","sequence":"first","affiliation":[{"name":"College of Chemistry and Chemical Engineering Guangxi University  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6504-6427","authenticated-orcid":false,"given":"Yongquan","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering Guangxi University  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zexu","family":"Xing","sequence":"additional","affiliation":[{"name":"Medical College Guangxi University  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9043-3162","authenticated-orcid":false,"given":"Lihe","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Youjiang Medical University for Nationalities  Baise China"},{"name":"Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening Guangxi Medical University  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2655-0724","authenticated-orcid":false,"given":"Lisheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical College Guangxi University  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01200-4"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01460-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13353"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-32-16"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.3104"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2021.127788"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-014-2626-2"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2903"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1683"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0182"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25611"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.19594"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"e0169323","DOI":"10.1371\/journal.pone.0169323","article-title":"Contrast\u2010Enhanced Ultrasound with VEGFR2\u2010Targeted Microbubbles for Monitoring Regorafenib Therapy Effects in Experimental Colorectal Adenocarcinomas in Rats with DCE\u2010MRI and Immunohistochemical Validation","volume":"12","author":"Chammas R.","year":"2017","journal-title":"Plos One"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0264"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-824X-6-18"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.111609"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.113083"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107626"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107829"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22060913"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105358"},{"key":"e_1_2_11_23_1","unstructured":"D. H.Dawood ChemistrySelect10(2025):e202404767."},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13061355"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00588"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmcr.2022.100098"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/17568919.2025.2515815"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2013-3"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.140747"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202000979"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchbi.2024.1398873"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.138012"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112752"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21974"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-019-01934-9"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5QO01408E"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202402065"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c17554"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.4314\/bcse.v33i2.12"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116348"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.108482"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70283","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.70283","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70283","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:38:22Z","timestamp":1777516702000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.70283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,25]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,4,28]]}},"alternative-id":["10.1002\/cmdc.70283"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.70283","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,25]]},"assertion":[{"value":"2025-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70283"}}