{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:05:27Z","timestamp":1789603527698,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"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":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Novel heterocyclic derivatives (<jats:bold>4\u201322<\/jats:bold>) were designed, synthesized, and evaluated against hepatocellular carcinoma type (HepG2) and breast cancer (MCF\u20107) cells, targeting the VEGFR\u20102 enzyme. Compounds <jats:bold>18<\/jats:bold>, <jats:bold>10<\/jats:bold>, <jats:bold>13<\/jats:bold>, <jats:bold>11<\/jats:bold>, and <jats:bold>14<\/jats:bold> were found to be the most potent derivatives against both the HepG2 and MCF\u20107 cancer cell lines, with GI<jats:sub>50<\/jats:sub>\u2009=\u20092.11, 2.54\u2009\u00b5M, 3.16, 3.64\u2009\u00b5M, 3.24, 6.99\u2009\u00b5M, 7.41, 6.49\u2009\u00b5M and 8.08, 10.46\u2009\u00b5M, respectively. Compounds <jats:bold>18<\/jats:bold> and <jats:bold>10<\/jats:bold> showed higher activities against both HepG2 and MCF\u20107 cells than sorafenib (GI<jats:sub>50<\/jats:sub>\u2009=\u20099.18, 5.47\u2009\u00b5M, respectively) and doxorubicin (GI<jats:sub>50<\/jats:sub>\u2009=\u20097.94, 8.07\u2009\u00b5M, respectively). Compounds <jats:bold>13<\/jats:bold>, <jats:bold>11<\/jats:bold>, and <jats:bold>14<\/jats:bold> showed higher activities than sorafenib against HepG2 cancer cells, but lower activities against MCF\u20107 cells. Compounds <jats:bold>18<\/jats:bold>, <jats:bold>13<\/jats:bold>, and <jats:bold>10<\/jats:bold> were more potent than sorafenib, inhibiting vascular endothelial growth factor receptor\u20102 (VEGFR\u20102) at GI<jats:sub>50<\/jats:sub> values of 0.05, 0.06, and 0.08\u2009\u00b5M, respectively. Compound <jats:bold>11<\/jats:bold> inhibited VEGFR\u20102 at an IC<jats:sub>50<\/jats:sub> value of 0.10\u2009\u00b5M, which is equipotent to sorafenib. Compound <jats:bold>14<\/jats:bold> inhibited VEGFR\u20102 at an IC<jats:sub>50<\/jats:sub> value of 0.11\u2009\u00b5M, which is nearly equipotent to sorafenib. The tested compounds have more selectivity against cancer cell lines. Compounds <jats:bold>18<\/jats:bold>, <jats:bold>10<\/jats:bold>, <jats:bold>13<\/jats:bold>, <jats:bold>11<\/jats:bold>, and <jats:bold>14<\/jats:bold> are, respectively, 16.76, 9.24, 6.06, 2.78, and 2.85 times more toxic in HePpG2 cancer cells than in VERO normal cells. Also, compounds <jats:bold>18<\/jats:bold>, <jats:bold>10<\/jats:bold>, <jats:bold>13<\/jats:bold>, <jats:bold>11<\/jats:bold>, and <jats:bold>14<\/jats:bold> are, respectively, 14.07, 8.02, 2.81, 3.18, and 2.20 times more toxic in MCF\u20107 than in VERO normal cells. The most active compounds, <jats:bold>10<\/jats:bold>, <jats:bold>13<\/jats:bold>, and <jats:bold>18<\/jats:bold>, showed a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile.<\/jats:p>","DOI":"10.1002\/ardp.202100237","type":"journal-article","created":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T07:21:50Z","timestamp":1638602510000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Design, synthesis, anticancer, and docking of some S\u2010 and\/or N\u2010heterocyclic derivatives as VEGFR\u20102 inhibitors"],"prefix":"10.1002","volume":"355","author":[{"given":"Khaled","family":"El\u2010Adl","sequence":"first","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry and Drug Design Department, Faculty of Pharmacy (Boys) Al\u2010Azhar University Nasr City Cairo Egypt"},{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Heliopolis University for Sustainable Development Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel A.\u2010H.","family":"Abdel\u2010Rahman","sequence":"additional","affiliation":[{"name":"Chemistry Department Menoufia University Shebin El\u2010Koam Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa M.","family":"Omar","sequence":"additional","affiliation":[{"name":"Chemistry Department Menoufia University Shebin El\u2010Koam Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Alswah","sequence":"additional","affiliation":[{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nashwa M.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Chemistry Al\u2010Azhar University (Girls Branch) Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-46144-3.00030-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2004.11.015"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c02038"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep30886"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000488087"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10121673"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2008.11.008"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2015.10.021"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.02.029"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2010.09.002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2013.11.029"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","unstructured":"F.Khedr M.\u2010K.Ibrahim I. 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