{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T20:09:53Z","timestamp":1789157393600,"version":"build-2803163510"},"reference-count":126,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cancer is a worldwide health burden that influences about every geographic location and socioeconomic class. One of the main challenges that remains is the appearance of resistance to cancer therapy. It is found that vascular endothelial growth factor receptor 2 (VEGFR\u20102) is overexpressed in a number of tumours. Few FDA approved drugs (such as Sorafenib, Sunitinib, Nintedanib and Cabotanzinib), which target VEGFRs, however, a significant issue with the monotherapy of these agents is drug resistance. Hence, in the present work. Some isatin\u2010aromatic amides (\n                    <jats:bold>5a\u2013q<\/jats:bold>\n                    ) were synthesised via Ag(I)\u2010NHC\/TBHP\u2010promoted tandem one\u2010pot oxidative amidation between 3\u2010((3\u2010hydroxypropyl)imino)\u20101\u2010methylindolin\u20102\u2010one (\n                    <jats:bold>3<\/jats:bold>\n                    ) and anilines (\n                    <jats:bold>4a\u2013q<\/jats:bold>\n                    ) in water as a key approach. The anti\u2010proliferative activity of amides (\n                    <jats:bold>5a\u2013q<\/jats:bold>\n                    ) revealed that compound\n                    <jats:bold>5j<\/jats:bold>\n                    (50% inhibitory concentration [IC\n                    <jats:sub>50<\/jats:sub>\n                    ] = &lt;2 \u00b5M) displayed superior activity against MCF\u20107 and HepG\u20102 cell lines than the standard drug Sunitinib (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 2.2\u20134.8 \u00b5M). Compounds\n                    <jats:bold>5d<\/jats:bold>\n                    and\n                    <jats:bold>5n<\/jats:bold>\n                    showed greater activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    = &lt;4 \u00b5M) against MCF\u20107 than the positive control (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 4.8 \u00b5M). In addition, compound\n                    <jats:bold>5d<\/jats:bold>\n                    had a comparable activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 2.5 \u00b5M) against HepG2 to the positive control (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 2.2 \u00b5M). As well, compounds\n                    <jats:bold>5d<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.09 \u00b5M) and\n                    <jats:bold>5j<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.06 \u00b5M) were found to be 1.55\u2010 and 2.33\u2010fold, respectively, more active against VEGFR\u20102 inhibition than Sunitinib (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.14 \u00b5M). Compound\n                    <jats:bold>5n<\/jats:bold>\n                    showed comparable (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.16 \u00b5M) VEGFR\u20102 inhibition to Sunitinib. Furthermore, in vitro bioavailability studies showed that compound\n                    <jats:bold>5n<\/jats:bold>\n                    crossed the Caco2 cell membrane and showed the highest intracellular concentration after sixth hour incubation, in comparison to compounds\n                    <jats:bold>5d<\/jats:bold>\n                    ,\n                    <jats:bold>5j<\/jats:bold>\n                    and Sunitinib. Finally, in silico molecular docking studies on VEGFR\u20102 (PDB ID 3VHE) revealed that compounds\n                    <jats:bold>5d<\/jats:bold>\n                    ,\n                    <jats:bold>5j<\/jats:bold>\n                    , and\n                    <jats:bold>5q<\/jats:bold>\n                    showed encouraging inhibition constants (68.5\u2013154.92\u00a0nM) and binding energies (\u22129.29 to \u22129.77\u00a0kcal\/mol) compared to Sunitinib (inhibition constant = 248.72\u00a0nM) and binding energy = \u22129.01\u00a0kcal\/mol). Specifically, compounds\n                    <jats:bold>5d<\/jats:bold>\n                    and\n                    <jats:bold>5j<\/jats:bold>\n                    established an H\u2010bond with the ASP1046 residue, similar to the standard drug Sunitinib.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202502894","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:25:38Z","timestamp":1770884738000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ImesAgCl\/TBHP Promoted Aqueous Synthesis of Isatin\u2010Amide Derivatives: Anti\u2010proliferative, Anti\u2010Vascular Endothelial Growth Factor Receptor 2, Bioavailability and Molecular Docking Studies"],"prefix":"10.1002","volume":"23","author":[{"given":"Gade","family":"Narmada","sequence":"first","affiliation":[{"name":"Department of Chemistry Chaitanya (Deemed to Be University), College of Science, King Saud University  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. N.","family":"Lohith","sequence":"additional","affiliation":[{"name":"Department of Physics Government First Grade College  Tumakuru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murali Krishna","family":"Thupurani","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Chaitanya (Deemed to Be University)  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhartha","family":"Marupati","sequence":"additional","affiliation":[{"name":"Department of Chemistry Vardhaman College of Engineering (Autonomous)  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharavath","family":"Ashok","sequence":"additional","affiliation":[{"name":"Department of Forensic Science Chaitanya (Deemed to Be University)  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thirukovela","family":"Narasimha Swamy","sequence":"additional","affiliation":[{"name":"Department of Chemistry Chaitanya (Deemed to Be University), College of Science, King Saud University  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.5888\/pcd15.180151"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.11.059"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026620666200128144825"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1515\/hc\u20102022\u20100179"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.5530\/ijper.58.1s.3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rechem.2025.102182"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.139743"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.139699"},{"key":"e_1_2_9_10_1","first-page":"404","article-title":"Targeting Vascular Endothelial Growth Receptor\u20102 (VEGFR\u20102): Structural Biology, Functional Insights, and Therapeutic Resistance","volume":"225","author":"Shah F. 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