{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:58:14Z","timestamp":1791165494548,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T00:00:00Z","timestamp":1620950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT - Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["Base Fund UIDB\/00674\/2020 and Programmatic Fund UIDP\/00674\/2020"],"award-info":[{"award-number":["Base Fund UIDB\/00674\/2020 and Programmatic Fund UIDP\/00674\/2020"]}]},{"name":"ARDITI- Ag\u00eancia Regional para o Desenvolvimento da Investiga\u00e7\u00e3o Tecnologia e Inova\u00e7\u00e3o","award":["M1420-01-0145-FEDER-000005-CQM+ and M1420-09-5369-FSE-000001 (C.C.)."],"award-info":[{"award-number":["M1420-01-0145-FEDER-000005-CQM+ and M1420-09-5369-FSE-000001 (C.C.)."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The DACHPtCl2 compound (trans-(R,R)-1,2-diaminocyclohexanedichloroplatinum(II)) is a potent anticancer drug with a broad spectrum of activity and is less toxic than oxaliplatin (trans-l-diaminocyclohexane oxalate platinum II), with which it shares the active metal fragment DACHPt. Nevertheless, due to poor water solubility, its use as a chemotherapeutic drug is limited. Here, DACHPtCl2 was conjugated, in a bidentate form, with half-generation PAMAM dendrimers (G0.5\u2013G3.5) with carboxylate end-groups, and the resulting conjugates were evaluated against various types of cancer cell lines. In this way, we aimed at increasing the solubility and availability at the target site of DACHPt while potentially reducing the adverse side effects. DNA binding assays showed a hyperchromic effect compatible with DNA helix\u2019s disruption upon the interaction of the metallodendrimers and\/or the released active metallic fragments with DNA. Furthermore, the prepared DACHPt metallodendrimers presented cytotoxicity in a wide set of cancer cell lines used (the relative potency regarding oxaliplatin was in general high) and were not hemotoxic. Importantly, their selectivity for A2780 and CACO-2 cancer cells with respect to non-cancer cells was particularly high. Subsequently, the anticancer drug 5-FU was loaded in a selected metallodendrimer (the G2.5COO(DACHPt)16) to investigate a possible synergistic effect between the two drugs carried by the same dendrimer scaffold and tested for cytotoxicity in A2780cisR and CACO-2 cancer cell lines. This combination resulted in IC50 values much lower than the IC50 for 5-FU but higher than those found for the metallodendrimers without 5-FU. It seems, thus, that the metallic fragment-induced cytotoxicity dominates over the cytotoxicity of 5-FU in the set of considered cell lines.<\/jats:p>","DOI":"10.3390\/molecules26102924","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T10:54:22Z","timestamp":1620989662000},"page":"2924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Use of Half-Generation PAMAM Dendrimers (G0.5\u2013G3.5) with Carboxylate End-Groups to Improve the DACHPtCl2 and 5-FU Efficacy as Anticancer Drugs"],"prefix":"10.3390","volume":"26","author":[{"given":"Cl\u00e1udia","family":"Camacho","sequence":"first","affiliation":[{"name":"CQM-Centro de Qu\u00edmica da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7856-2041","authenticated-orcid":false,"given":"Helena","family":"Tom\u00e1s","sequence":"additional","affiliation":[{"name":"CQM-Centro de Qu\u00edmica da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-1953","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"CQM-Centro de Qu\u00edmica da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal"},{"name":"School of Materials Science and Engineering, Center for Nano Energy Materials, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,14]]},"reference":[{"key":"ref_1","first-page":"1529","article-title":"Metals and metal compounds in cancer treatment","volume":"24","author":"Desoize","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1021\/acs.chemrev.5b00597","article-title":"The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs","volume":"116","author":"Johnstone","year":"2016","journal-title":"Chem. 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