{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:07:53Z","timestamp":1789348073047,"version":"build-2803163510"},"reference-count":70,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ\u201002393\u201024"],"award-info":[{"award-number":["APQ\u201002393\u201024"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ\u201000864\u201025"],"award-info":[{"award-number":["APQ\u201000864\u201025"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ\u201002185\u201024"],"award-info":[{"award-number":["APQ\u201002185\u201024"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["RED\u201000110\u201023"],"award-info":[{"award-number":["RED\u201000110\u201023"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ\u201002533\u201023"],"award-info":[{"award-number":["APQ\u201002533\u201023"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["407282\/2023\u20108"],"award-info":[{"award-number":["407282\/2023\u20108"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["308094\/2025\u20105"],"award-info":[{"award-number":["308094\/2025\u20105"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["300079\/2025\u20107"],"award-info":[{"award-number":["300079\/2025\u20107"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303853\/2025\u20105"],"award-info":[{"award-number":["303853\/2025\u20105"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["PROEX"],"award-info":[{"award-number":["PROEX"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,9,14]]},"abstract":"<jats:p>Photodynamic therapy (PDT) is a clinically established approach that relies on the localized generation of reactive oxygen species (ROS) mediated by a photosensitizer (PS), light, and molecular oxygen. Protoporphyrin IX (PpIX) is an approved PS; however, its intracellular retention is limited, factor that can alter its overall photodynamic efficiency. In this study, we report how the design of PpIX derivatives bearing piperazine (PpIX\u2010Pip) or morpholine (PpIX\u2010Morp) substituents may modulate lipophilicity, cellular uptake, oxidative stress, and phototoxicity. The photodynamic activity of these derivatives was evaluated in the aggressive triple\u2010negative human breast cancer cell line MDA\u2010MB\u2010231. Both derivatives showed greater time\u2010dependent cellular retention and enhanced photodynamic activity compared to PpIX, promoting oxidative stress, and triggering loss of mitochondrial membrane potential and caspase\u20103 activation. These results highlight the impact of rational structural modification of PpIX on photodynamic efficiency and provide valuable structure\u2013activity relationship insights for the development of improved porphyrin\u2010based PS for PDT.<\/jats:p>","DOI":"10.1002\/cmdc.70471","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:13:51Z","timestamp":1787969631000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Piperazine and Morpholine Protoporphyrin IX Derivatives Intensify Biomolecules Oxidation and Phototoxicity in Triple\u2010Negative Breast Cancer"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1392-1433","authenticated-orcid":false,"given":"Maynne Duarte Suriani","family":"Franco","sequence":"first","affiliation":[{"name":"Institute of Chemistry Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2347-9515","authenticated-orcid":false,"given":"Thibault Joseph William Jacques Dit","family":"Lapierre","sequence":"additional","affiliation":[{"name":"Institute of Chemistry Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarcisio Paiva","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9896-5550","authenticated-orcid":false,"given":"Luiz Felipe Fernandes","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Roland","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce Ferreira Da Costa","family":"Guerra","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0329-5521","authenticated-orcid":false,"given":"Kelly Aparecida Geraldo Yoneyama","family":"Tudini","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele Lisboa","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6937-1411","authenticated-orcid":false,"given":"Foued Salmen","family":"Espindola","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3616-6611","authenticated-orcid":false,"given":"Allisson Benetti","family":"Justino","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso de Oliveira","family":"Rezende J\u00fanior","sequence":"additional","affiliation":[{"name":"Institute of Chemistry Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"},{"name":"Department of Chemistry Federal University of Juiz de Fora  Juiz de Fora Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4795-4568","authenticated-orcid":false,"given":"Tayana Mazin","family":"Tsubone","sequence":"additional","affiliation":[{"name":"Institute of Chemistry Federal University of Uberlandia  Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"American Cancer Society Photodynamic Therapy. Science Progress 2025 https:\/\/www.cancer.org\/cancer\/managing\u2010cancer\/treatment\u2010types\/photodynamic\u2010therapy.html."},{"key":"e_1_2_9_3_1","unstructured":"F. C.Rossetti Nanodispers\u00f5es De Cristais l\u00edquidos Como Sistemas De Libera\u00e7\u00e3o De Fotossensibilizadores NA Terapia Fotodin\u00e2mica Do c\u00e2ncer De Pele: Avalia\u00e7\u00e3o In Vitro e In Vivo DA Permea\u00e7\u00e3o e Reten\u00e7\u00e3o Cut\u00e2neas 2010."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030585"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1476228"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers3022516"},{"key":"e_1_2_9_7_1","unstructured":"American Cancer Society Photodynamic Therapy (PDT) 2025 https:\/\/www.cancer.org\/cancer\/managing\u2010cancer\/treatment\u2010types\/photodynamic\u2010therapy.html?utm_source=chatgpt.com."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13091332"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.RECHEM.2024.101715"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2019.106263"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002140\u2010y"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1590\/0001\u20103765201820170811"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20189"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","unstructured":"D.SharmaandD.Sengupta \u201cPorphyrins in Photodynamic Therapy: A Review \u201d ChemRxiv 2023 https:\/\/doi.org\/10.26434\/chemrxiv\u20102023\u2010j1tc1.","DOI":"10.26434\/chemrxiv-2023-j1tc1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1142\/S108842461000263X"},{"key":"e_1_2_9_16_1","unstructured":"B. A.Iglesias S\u00edntese e Propriedades Espectrosc\u00f3picas e Eletroqu\u00edmicas De Uma Triazeno\u2010Porfirina 2012."},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2852(61)90236-3"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/17568919.2025.2515813"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.5095911"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/chemosensors10080340"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082786"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CCR.2025.216526"},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","unstructured":"S.Satapathy S.Kumar V.Nigam et al. \u201cCaspases Activity Assay Procedures Caspases as Molecular Targets for Cancer Therapy \u201d2024 199\u2013229 https:\/\/doi.org\/10.1016\/B978\u20100\u2010443\u201015644\u20101.00009\u20102.","DOI":"10.1016\/B978-0-443-15644-1.00009-2"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400476"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0dt03569f"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272\u2010012\u20100105\u2010z"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2016.1189902"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.07.026"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2021.1931861"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00052"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.synthmet.2017.05.006"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dyepig.2019.03.002"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/2055\u20107124\u201018\u201019"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.DYEPIG.2025.112649"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228716"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201006788\u20107"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20101759(83)90303\u20104"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20106960\u20109"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201063491\u2010w"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003\u20102697(76)90527\u20103"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003\u20109861(59)90090\u20106"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304\u20103940(01)01636\u20106"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CCA.2012.01.038"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1974.tb03714.x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076\u20106879(84)05016\u20103"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1006\/ABIO.1996.0292"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.MATCHEMPHYS.2024.129557"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2000.1714"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43630\u2010023\u201000382\u20109"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.378"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179591"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.TETLET.2007.03.085"},{"key":"e_1_2_9_53_1","first-page":"1","article-title":"Oecd Gu Id Elin e for the Tes Tin g of Chemicals","volume":"8","author":"Oecd\/Ocde","year":"1992","journal-title":"Guideline for Testing of Chemicals"},{"key":"e_1_2_9_54_1","volume-title":"Princ\u00edpios De Bioqu\u00edmica De Lehninger","author":"Nelson D. L.","year":"2014"},{"key":"e_1_2_9_55_1","doi-asserted-by":"crossref","unstructured":"Q.Qi R.Gu J.Zhu K. E.Anderson andX.Ma \u201cRoles of the ABCG2 Transporter in Protoporphyrin IX Distribution and Toxicity Drug Metabolism and Disposition \u201d52(2024):1201\u20131207 https:\/\/doi.org\/10.1124\/DMD.123.001582.","DOI":"10.1124\/dmd.123.001582"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102004\u201004\u20101566"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1070"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1572\u20101000(05)00007\u20104"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.PDPDT.2020.101854"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097\u20100142(19970615)79:123.0.CO;2\u2010O"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01666038"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.75"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7167"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.8b00692"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.REDOX.2025.103859"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44318\u2010025\u201000632\u20109"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BBCAN.2007.07.001"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400446"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1039\/b108586g"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1309"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.2.990"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70471","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.70471","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70471","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:46:23Z","timestamp":1789346783000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.70471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":70,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2026,9,14]]}},"alternative-id":["10.1002\/cmdc.70471"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.70471","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"assertion":[{"value":"2026-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70471"}}