{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:00:52Z","timestamp":1788328852867,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Deanship of Research and Graduate Studies at King Khalid University through small group research","award":["RGP1\/213\/46"],"award-info":[{"award-number":["RGP1\/213\/46"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Herein, a novel series of 4-piperidinylphenyl-linked thiazoles was synthesized as VEGFR2 inhibitors with potential cytotoxic activity against renal cancer. Most of the target compounds inhibited VEGFR2 enzyme at sub-micromolar IC50 values. Compounds 7c (IC50 = 0.073 \u00b1 0.002 \u00b5M), 9b (IC50 = 0.049 \u00b1 0.002 \u00b5M), and 9c (IC50 = 0.093 \u00b1 0.003 \u00b5M) were the most potent, showing VEGFR2 inhibition superior to that of sunitinib (IC50 = 0.118 \u00b1 0.003 \u00b5M). Furthermore, compounds 7c, 9b, and 9c effectively inhibited the growth of A498 renal cancer cells, with compound 7c being the most potent showing a one-digit IC50 value of 7.866 \u00b1 0.27 \u00b5M. In addition, compound 7c revealed a potentially improved safety profile against non-cancerous normal cells, relative to sunitinib. The treatment of A498 renal cancer cells with compound 7c led to an apparent cell cycle arrest and a significant induction of apoptosis. A docking study was also conducted and revealed a proper orientation of compound 7c into the active site of VEGFR2.<\/jats:p>","DOI":"10.3390\/biom16030370","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:55:01Z","timestamp":1772463301000},"page":"370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["New Derivatives of 4-Piperidinylphenyl-Linked Thiazoles as VEGFR2 Inhibitors with Potential Cytotoxicity Against Renal Cancer"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4300-2785","authenticated-orcid":false,"given":"Huda K.","family":"Mahmoud","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thoraya A.","family":"Farghaly","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt"},{"name":"Department of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossa F.","family":"Alshareef","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2919-0330","authenticated-orcid":false,"given":"Amani M. R.","family":"Alsaedi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Collage of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afaf Y.","family":"Khormi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan Gaber","family":"Abdulwahab","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa M.","family":"Abu Alnjaa","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Jamoum University College, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadia M.","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Cairo University Hospital, University of Cairo, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/s41580-023-00631-w","article-title":"Biology and therapeutic targeting of vascular endothelial growth factor A","volume":"24","author":"Ferrara","year":"2023","journal-title":"Nat. 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