{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:51:38Z","timestamp":1761598298831,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54CA199092"],"award-info":[{"award-number":["U54CA199092"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005699","name":"Universit\u00e0 degli Studi del Piemonte Orientale","doi-asserted-by":"publisher","award":["Progetto Ricerca Locale 2019"],"award-info":[{"award-number":["Progetto Ricerca Locale 2019"]}],"id":[{"id":"10.13039\/501100005699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Symmetry"],"abstract":"<jats:p>Boron Neutron Capture Therapy (BNCT) is a binary therapy that promises to be suitable in treating many non-curable cancers. To that, the discovery of new boron compounds able to accumulate selectively in the tumour tissue is still required. Hypoxia, a deficiency of oxygen in tumor tissue, is a great challenge in the conventional treatment of cancer, because hypoxic areas are resistant to conventional anticancer treatments. 2-Nitroimidazole derivatives are known to be hypoxia markers due to their enrichment by bioreduction in hypoxic cells. In the present work, 2-nitroimidazole was chosen as the starting point for the synthesis of a new boron-containing compound based on a 1,3,5-triazine skeleton. Two o-carborane moieties were inserted to achieve a high ratio of boron on the molecular weight, exploiting a short PEG spacer to enhance the polarity of the compound and outdistance the active part from the core. The compound showed no toxicity on normal human primary fibroblasts, while it showed noteworthy toxicity in multiple myeloma cells together with a consistent intracellular boron accumulation.<\/jats:p>","DOI":"10.3390\/sym13020202","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T12:20:26Z","timestamp":1611750026000},"page":"202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis and Characterisation of a Boron-Rich Symmetric Triazine Bearing a Hypoxia-Targeting Nitroimidazole Moiety"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2147-6804","authenticated-orcid":false,"given":"Tobias Hartwig","family":"B\u00fcnning","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze del Farmaco, Universit\u00e0 del Piemonte Orientale, L.go Donegani, 2\u201428100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-0409","authenticated-orcid":false,"given":"Luigi","family":"Panza","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze del Farmaco, Universit\u00e0 del Piemonte Orientale, L.go Donegani, 2\u201428100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6371-2780","authenticated-orcid":false,"given":"Abdel Kareem","family":"Azab","sequence":"additional","affiliation":[{"name":"Cancer Biology Division, Department of Radiation Oncology, Washington University School of Medicine in St. Louis, 4511 Forest Park Ave, Room 3103, St. Louis, MO 63108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4125-4624","authenticated-orcid":false,"given":"Barbara","family":"Muz","sequence":"additional","affiliation":[{"name":"Cancer Biology Division, Department of Radiation Oncology, Washington University School of Medicine in St. Louis, 4511 Forest Park Ave, Room 3103, St. Louis, MO 63108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Fallarini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze del Farmaco, Universit\u00e0 del Piemonte Orientale, L.go Donegani, 2\u201428100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6810-1439","authenticated-orcid":false,"given":"Daniela","family":"Imperio","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze del Farmaco, Universit\u00e0 del Piemonte Orientale, L.go Donegani, 2\u201428100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"ref_1","first-page":"ZE01","article-title":"Boron neutron capture therapy\u2014A literature review","volume":"10","author":"Nedunchezhian","year":"2016","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.rpor.2018.07.002","article-title":"Physical, dosimetric and clinical aspects and delivery systems in neutron capture therapy","volume":"23","author":"Farhood","year":"2018","journal-title":"Rep. Pract. Oncol. Radiother."},{"key":"ref_3","first-page":"36","article-title":"A realistic appraisal of boron neutron capture therapy as a cancer treatment modality","volume":"38","author":"Barth","year":"2018","journal-title":"Cancer Commun."},{"key":"ref_4","first-page":"174","article-title":"New horizons for therapy based on the boron neutron capture reaction","volume":"4","author":"Hawthorne","year":"1998","journal-title":"Trends Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1111\/j.1349-7006.2009.01195.x","article-title":"Significance of nitroimidazole compounds and hypoxia-inducible factor-1 for imaging tumor hypoxia","volume":"100","year":"2009","journal-title":"Cancer Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s10967-017-5210-5","article-title":"Synthesis of novel PEG-modified nitroimidazole derivatives via \u201chot-click\u201d reaction and their biological evaluation as potential PET imaging agent for tumors","volume":"312","author":"Cao","year":"2017","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_7","first-page":"3700","article-title":"A new and improved synthesis of the precursor of the hypoxia marker [\u00b98F]-FMISO","volume":"21","author":"Nieto","year":"2010","journal-title":"Synthesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/0969-8051(94)90025-6","article-title":"Synthesis and radioiodination of a nido-1,2-carboranyl derivative of 2-nitroimidazole","volume":"21","author":"Wilbur","year":"1994","journal-title":"Nucl. Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.apradiso.2004.05.018","article-title":"The usefulness of 2-nitroimidazole-sodium borocaptate-10B conjugates as 10B-carriers in boron neutron capture therapy","volume":"61","author":"Masunaga","year":"2004","journal-title":"Appl. Radiat. Isot."},{"key":"ref_10","first-page":"2975","article-title":"Applicability of the 2-nitroimidazole-sodium borocaptate-10B conjugate, TX-2060, as a 10B-carrier in boron neutron capture therapy","volume":"24","author":"Masunaga","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1021\/acs.molpharmaceut.9b00898","article-title":"Application of nitroimidazole\u2013carborane-modified phenylalanine derivatives as dual-target boron carriers in boron neutron capture therapy","volume":"17","author":"Li","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1007\/s11095-016-1977-2","article-title":"A hypoxia-targeted boron neutron capture therapy agent for the treatment of glioma","volume":"33","author":"Luderer","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1021\/cr00010a002","article-title":"Dicarba-closo-dodecaboranes C2B10H12 and their derivatives","volume":"92","author":"Bregadze","year":"1992","journal-title":"Chem. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10834","DOI":"10.1039\/C9DT02130B","article-title":"Modular triazine-based carborane-containing carboxylic acids\u2014Synthesis and characterisation of potential boron neutron capture therapy agents made of readily accessible building blocks","volume":"48","author":"Kellert","year":"2019","journal-title":"Dalton Trans."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1039\/C9DT04031E","article-title":"Tuning a modular system\u2013synthesis and characterisation of a boron-rich s-triazine-based carboxylic acid and amine bearing a galactopyranosyl moiety","volume":"49","author":"Kellert","year":"2020","journal-title":"Dalton Trans."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ronchi, S., Prosperi, D., Compostella, F., and Panza, L. (2004). Synthesis of novel carborane-hybrids based on a triazine scaffold for boron neutron capture therapy. 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Sci."},{"key":"ref_20","first-page":"670","article-title":"Hyaluronan as carrier of carboranes for tumor targeting in boron neutron capture therapy","volume":"8","author":"Panza","year":"2008","journal-title":"Biomacromolecules"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8914","DOI":"10.1021\/ja0041369","article-title":"Orthogonal, convergent syntheses of dendrimers based on melamine with one or two unique surface sites for manipulation","volume":"123","author":"Zhang","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1021\/bc500034n","article-title":"Triazine-based tool box for developing peptidic PET imaging probes: Syntheses, microfluidic radiolabeling, and structure\u2013Activity evaluation","volume":"25","author":"Li","year":"2014","journal-title":"Bioconjugate Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1016\/j.tet.2016.07.044","article-title":"Advances of azide-alkyne cycloaddition-click chemistry over the recent decade","volume":"72","author":"Singh","year":"2016","journal-title":"Tetrahedron"}],"container-title":["Symmetry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-8994\/13\/2\/202\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:16:04Z","timestamp":1760159764000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-8994\/13\/2\/202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,27]]},"references-count":23,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["sym13020202"],"URL":"https:\/\/doi.org\/10.3390\/sym13020202","relation":{},"ISSN":["2073-8994"],"issn-type":[{"type":"electronic","value":"2073-8994"}],"subject":[],"published":{"date-parts":[[2021,1,27]]}}}