{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T09:19:47Z","timestamp":1770974387067,"version":"3.50.1"},"reference-count":85,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2021,12,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite the advances in developing MMP\u20102\/9 inhibitors, off\u2010target side effects and pharmacokinetics problems remain major challenges hindering their clinical success in cancer therapy. However, recent targeting strategies have clearly revitalized MMP research. Herein, we introduce new <jats:italic>s<\/jats:italic>\u2010triazine\u2010based dendrimers endowed with intrinsic MMP\u20102\/9 inhibitory potential and tetherable to hepatocellular carcinoma\u2010specific targeting ligands and anticancer agents <jats:italic>via<\/jats:italic> biodegradable linkages for targeted therapy. The designed dendrimeric platform was built with potential zinc\u2010binding branching linkers (hydrazides) and termini (carboxylic acids and hydrazides) to confer potency against MMP\u20102\/9. Preliminary cytotoxicity screening and MMP\u20102\/9 inhibition assay of the free dendrimers revealed promising potency (MMP\u20109; IC<jats:sub>50<\/jats:sub>=0.35\u20130.57\u2005\u03bcM, MMP\u20102; IC<jats:sub>50<\/jats:sub>=0.39\u20130.77\u2005\u03bcM) within their safe doses (EC<jats:sub>100<\/jats:sub>=94.15\u201342.75\u2005\u03bcM). The hydrazide dendrimer was comparable to NNGH and superior to the carboxylic acid analogue. MTT assay showed that the free dendrimers were superior to the reference anticancer agent honokiol. Their anticancer potency was enhanced by HK conjugation, targeting ligands installation and PEGylation as exemplified by the hydrazide dendrimer conjugate <jats:bold>(TPG<jats:sub>3<\/jats:sub>\u2212NH<jats:sub>2<\/jats:sub>)\u2010SuHK\u2010FA\u2010SuPEG<\/jats:bold> (Huh\u20107; IC<jats:sub>50<\/jats:sub>=5.54\u2005\u03bcM, HepG\u20102; IC<jats:sub>50<\/jats:sub>=10.07\u2005\u03bcM) being 4 folds more active than HK, followed by the carboxylic acid conjugate <jats:bold>(TPG<jats:sub>3<\/jats:sub>\u2212OH)\u2010HK\u2010LA\u2010PEG<\/jats:bold> (Huh\u20107; IC<jats:sub>50<\/jats:sub>=14.97, HepG\u20102; IC<jats:sub>50<\/jats:sub>=21.29\u2005\u03bcM). This was consistent with apoptosis studies.<\/jats:p>","DOI":"10.1002\/cmdc.202100465","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T16:59:02Z","timestamp":1632243542000},"page":"3701-3719","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Engineered <i>s<\/i>\u2010Triazine\u2010Based Dendrimer\u2010Honokiol Conjugates as Targeted MMP\u20102\/9 Inhibitors for Halting Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0096-2934","authenticated-orcid":false,"given":"Hosam H.","family":"Khalil","sequence":"first","affiliation":[{"name":"Chemistry Department, Faculty of Science Alexandria University  Alexandria 21321 Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heba A.","family":"Osman","sequence":"additional","affiliation":[{"name":"Department of Physics and Chemistry Faculty of Education Alexandria University  Alexandria 21526 Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9695-4404","authenticated-orcid":false,"given":"Mohamed","family":"Teleb","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Alexandria University  Alexandria 21521 Egypt"},{"name":"Cancer Nanotechnology Research Laboratory (CNRL) Faculty of Pharmacy Alexandria University  Alexandria 21521 Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. I.","family":"Darwish","sequence":"additional","affiliation":[{"name":"Department of Physics and Chemistry Faculty of Education Alexandria University  Alexandria 21526 Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8887-3727","authenticated-orcid":false,"given":"Marwa M.","family":"Abu\u2010Serie","sequence":"additional","affiliation":[{"name":"Medical Biotechnology Department Genetic Engineering and Biotechnology Research Institute City of Scientific Research and Technological Applications (SRTA-City)  Alexandria 21934 Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3162-6386","authenticated-orcid":false,"given":"Sherine N.","family":"Khattab","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science Alexandria University  Alexandria 21321 Egypt"},{"name":"Cancer Nanotechnology Research Laboratory (CNRL) Faculty of Pharmacy Alexandria University  Alexandria 21521 Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6043-2620","authenticated-orcid":false,"given":"Nesreen S.","family":"Haiba","sequence":"additional","affiliation":[{"name":"Department of Physics and Chemistry Faculty of Education Alexandria University  Alexandria 21526 Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,10]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.09.110193.002545"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19103028"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.015"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03096"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.17.1260"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1877"},{"key":"e_1_2_9_7_1","first-page":"26","volume":"2","author":"Cathcart J.","year":"2015","journal-title":"Genes Dev."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0424"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1139\/y99-055"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.02.014"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000070112.80711.3D"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2004.11.019"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(67)80055-X"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026043387854"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161207781039706"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.08.058"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612053382115"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2010.07919.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067100"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1821"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.15.3.253"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr9804543"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2009.08.006"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.041811af"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11224-020-01635-4"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92881-x"},{"key":"e_1_2_9_27_1","first-page":"319302","author":"Venugopal R.","year":"2021","journal-title":"Br. 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