{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:33:11Z","timestamp":1763375591024,"version":"3.45.0"},"reference-count":48,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>One of the best-known flavonoid chrysin was coupled at position 7 with several trisubstituted phosphine derivatives with a flexible spacer, and their in vitro anticancer activities were investigated on 60 human tumor cell lines (NCI60) and on several gynecological cancer cells. The trisubstituted phosphines contained different substituents on the aromatic ring(s), e.g., methyl and methoxy groups or fluoro atoms. The phosphorus atom was substituted not only with aromatic rings but with cyclohexyl substituents. The ionic phosphonium building block is important because it allows the therapeutic agents to transfer across the cell membrane. Therefore, the pharmacophores linked to it can exert their effects in the mitochondria. Instead of the ionic phosphonium element, a neutral moiety, namely the triphenylmethyl group, was also added to the side chain, being sterically similar but without a charge and phosphorus atom. Most of the hybrids exhibited low micromolar growth inhibition (GI50) values against the majority of the tested cell lines. Notably, conjugate 3f stood out, demonstrating nanomolar antitumor activity against the K-562 leukemia cell line (GI50 = 34 nM). One selected compound (3i) with promising cancer selectivity elicited cell cycle disturbances and inhibited the migration of breast cancer. The tumor-selectivity of 3a and 3f was assessed based on their effects on non-tumor Chinese hamster ovary (CHO) cells using the CellTiter-Glo Luminescent Cell Viability Assay. Given their estimated half-maximal inhibitory concentration (IC50) values on non-tumor CHO cells (2.65 \u00b5M and 1.15 \u00b5M, respectively), these conjugates demonstrate promising selectivity toward several cancer cell lines. The excellent results obtained may serve as good starting points for further optimization and the design of even more effective flavonoid- and\/or phosphonium-based drugs.<\/jats:p>","DOI":"10.3390\/ijms262211063","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:24:58Z","timestamp":1763375098000},"page":"11063","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and In Vitro Anticancer Evaluation of Novel Phosphonium Derivatives of Chrysin"],"prefix":"10.3390","volume":"26","author":[{"given":"M\u00f3nika","family":"Halmai","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, M\u0171egyetem rkp. 3, H-1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominika M\u00e1ria","family":"Herr","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, M\u0171egyetem rkp. 3, H-1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szabolcs","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, M\u0171egyetem rkp. 3, H-1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter","family":"Keglevich","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, M\u0171egyetem rkp. 3, H-1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5727-6348","authenticated-orcid":false,"given":"Ejlal A.","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Institute of Pharmacodynamics and Biopharmacy, University of Szeged, E\u00f6tv\u00f6s u. 6, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7907-7734","authenticated-orcid":false,"given":"No\u00e9mi","family":"B\u00f3zsity-Farag\u00f3","sequence":"additional","affiliation":[{"name":"Institute of Pharmacodynamics and Biopharmacy, University of Szeged, E\u00f6tv\u00f6s u. 6, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-5300","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Zupk\u00f3","sequence":"additional","affiliation":[{"name":"Institute of Pharmacodynamics and Biopharmacy, University of Szeged, E\u00f6tv\u00f6s u. 6, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Nehr-Majoros","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Centre for Neuroscience, University of P\u00e9cs, Szigeti \u00fat 12, H-7624 P\u00e9cs, Hungary"},{"name":"National Laboratory for Drug Research and Development, Magyar Tud\u00f3sok krt. 2, H-1117 Budapest, Hungary"},{"name":"HUN-REN PTE Chronic Pain Research Group, Szigeti \u00fat 12, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c9va","family":"Sz\u0151ke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Centre for Neuroscience, University of P\u00e9cs, Szigeti \u00fat 12, H-7624 P\u00e9cs, Hungary"},{"name":"National Laboratory for Drug Research and Development, Magyar Tud\u00f3sok krt. 2, H-1117 Budapest, Hungary"},{"name":"HUN-REN PTE Chronic Pain Research Group, Szigeti \u00fat 12, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Centre for Neuroscience, University of P\u00e9cs, Szigeti \u00fat 12, H-7624 P\u00e9cs, Hungary"},{"name":"National Laboratory for Drug Research and Development, Magyar Tud\u00f3sok krt. 2, H-1117 Budapest, Hungary"},{"name":"HUN-REN PTE Chronic Pain Research Group, Szigeti \u00fat 12, H-7624 P\u00e9cs, Hungary"},{"name":"PharmInVivo Ltd., Szondi Gy. u. 10, H-7629 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Hazai","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, M\u0171egyetem rkp. 3, H-1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cheng, X., Feng, D., Lv, J., Cui, X., Wang, Y., Wang, Q., and Zhang, L. 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