{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:49:04Z","timestamp":1792856944745,"version":"4.5.0"},"reference-count":92,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union and the Greek National Funds","award":["\u03a42\u0395\u0394\u039a 02056"],"award-info":[{"award-number":["\u03a42\u0395\u0394\u039a 02056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gonadotropin-releasing hormone (GnRH) is pivotal in regulating human reproduction and fertility through its specific receptors. Among these, gonadotropin-releasing hormone receptor type I (GnRHR I), which is a member of the G-protein-coupled receptor family, is expressed on the surface of both healthy and malignant cells. Its presence in cancer cells has positioned this receptor as a primary target for the development of novel anti-cancer agents. Moreover, the extensive regulatory functions of GnRH have underscored decapeptide as a prominent vehicle for targeted drug delivery, which is accomplished through the design of appropriate conjugates. On this basis, a rationally designed series of anthraquinone\/mitoxantrone\u2013GnRH conjugates (con1\u2013con8) has been synthesized herein. Their in vitro binding affinities range from 0.06 to 3.42 nM, with six of them (con2\u2013con7) demonstrating higher affinities for GnRH than the established drug leuprolide (0.64 nM). Among the mitoxantrone based GnRH conjugates, con3 and con7 show the highest affinities at 0.07 and 0.06 nM, respectively, while the disulfide bond present in the conjugates is found to be readily reduced by the thioredoxin (Trx) system. These findings are promising for further pharmacological evaluation of the synthesized conjugates with the prospect of performing future clinical studies.<\/jats:p>","DOI":"10.3390\/ijms242015232","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T08:32:57Z","timestamp":1697445177000},"page":"15232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Rational Design, Synthesis and Binding Affinity Studies of Anthraquinone Derivatives Conjugated to Gonadotropin-Releasing Hormone (GnRH) Analogues towards Selective Immunosuppression of Hormone-Dependent Cancer"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5789-8884","authenticated-orcid":false,"given":"Georgia","family":"Biniari","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Patras, 26504 Rion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9386-7169","authenticated-orcid":false,"given":"Christos","family":"Markatos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0022-3725","authenticated-orcid":false,"given":"Agathi","family":"Nteli","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Patras, 26504 Rion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1534-2762","authenticated-orcid":false,"given":"Haralambos","family":"Tzoupis","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Patras, 26504 Rion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7096-4281","authenticated-orcid":false,"given":"Carmen","family":"Simal","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Patras, 26504 Rion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5068-6459","authenticated-orcid":false,"given":"Alexios","family":"Vlamis-Gardikas","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Patras, 26504 Rion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlasios","family":"Karageorgos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4933-7723","authenticated-orcid":false,"given":"Ioannis","family":"Pirmettis","sequence":"additional","affiliation":[{"name":"Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research \u201cDemokritos\u201d, 15341 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Petrou","sequence":"additional","affiliation":[{"name":"Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research \u201cDemokritos\u201d, 15341 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3789-8032","authenticated-orcid":false,"given":"Maria","family":"Venihaki","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, School of Medicine, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Liapakis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1310-0591","authenticated-orcid":false,"given":"Theodore","family":"Tselios","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Patras, 26504 Rion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,16]]},"reference":[{"key":"ref_1","first-page":"1036","article-title":"Gonadotropin-Releasing Hormone: One Polypeptide Regulates of Luteinizing and Follicle-Stimulating Hormones","volume":"173","author":"Schally","year":"1971","journal-title":"Science 1979"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.2164-0947.1964.tb03484.x","article-title":"Hypothalamic Factors Which Influence Gonadotrophin Secretion","volume":"27","author":"McCann","year":"1964","journal-title":"Trans. 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