{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:45:28Z","timestamp":1783435528888,"version":"3.54.6"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Croatian Science Foundation","award":["IP-2013-5660"],"award-info":[{"award-number":["IP-2013-5660"]}]},{"name":"Croatian Science Foundation","award":["KK.01.1.1.02.0021"],"award-info":[{"award-number":["KK.01.1.1.02.0021"]}]},{"name":"European Regional Development Fund","award":["IP-2013-5660"],"award-info":[{"award-number":["IP-2013-5660"]}]},{"name":"European Regional Development Fund","award":["KK.01.1.1.02.0021"],"award-info":[{"award-number":["KK.01.1.1.02.0021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multidrug resistance (MDR) poses a significant challenge in cancer therapy, often leading to treatment failure and relapse. ATP-binding cassette (ABC) transporters, particularly ABCG2, play a pivotal role in MDR development by actively expelling chemotherapeutic agents from cancer cells. This study investigates the effects of two groups of primaquine derivatives\u2014fumardiamides (1a\u2013d) and bis-ureas (2a, b), both bearing halogenated benzene rings\u2014on the activity of P-glycoprotein (P-gp) and ABCG2. Their potential to reverse MDR was evaluated through a series of functional assays aimed at comparing transporter\u2013compound interactions. The results indicated that fumardiamide derivatives, specifically 1a, 1b, and 1d, exhibited potent inhibition of ABCG2 while having no effect on P-gp, demonstrating a selective mode of action. The tested derivatives displayed low to moderate cytotoxicity and did not affect ABCG2 expression or localization. Moreover, these compounds enhanced the sensitivity of drug-resistant cancer cell lines to mitoxantrone, underscoring their potential to overcome ABCG2-mediated MDR. These findings suggest that chemical modifications of primaquine, particularly the incorporation of fumardiamide moieties, confer novel biological properties, providing promising leads for the development of selective ABCG2 inhibitors.<\/jats:p>","DOI":"10.3390\/ijms26115367","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T11:55:52Z","timestamp":1748951752000},"page":"5367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Selective Inhibition of the ABCG2 Transporter by Primaquine Derivatives Reverses the Multidrug Resistance of Tumor Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5290-6945","authenticated-orcid":false,"given":"Marija","family":"Mio\u010d","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine, Ru\u0111er Bo\u0161kovi\u0107 Institute, Bijeni\u010dka c. 54, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9619-7156","authenticated-orcid":false,"given":"Maja","family":"Beus","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Zagreb Faculty of Pharmacy and Biochemistry, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7965-4018","authenticated-orcid":false,"given":"Karla","family":"Carevi\u0107","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Ru\u0111er Bo\u0161kovi\u0107 Institute, Bijeni\u010dka c. 54, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-1116","authenticated-orcid":false,"given":"Zrinka","family":"Raji\u0107","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Zagreb Faculty of Pharmacy and Biochemistry, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal\u00e1zs","family":"Sarkadi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tud\u00f3sok krt. 2, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0972-4606","authenticated-orcid":false,"given":"\u00c1gnes","family":"Telbisz","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tud\u00f3sok krt. 2, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-2722","authenticated-orcid":false,"given":"Marijeta","family":"Kralj","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Ru\u0111er Bo\u0161kovi\u0107 Institute, Bijeni\u010dka c. 54, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Catalano, A., Iacopetta, D., Ceramella, J., Scumaci, D., Giuzio, F., Saturnino, C., Aquaro, S., Rosano, C., and Sinicropi, M.S. 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