{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T04:21:01Z","timestamp":1770524461814,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-15-00321"],"award-info":[{"award-number":["23-15-00321"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Glucocorticoids (GCs) are routinely used to treat hematological malignancies; however, long-term treatment with GCs can lead to atrophic and metabolic adverse effects. Selective glucocorticoid receptor agonists (SEGRAs) with reduced side effects may act as a superior alternative to GCs. More than 30 SEGRAs have been described so far, yet none of them reached clinical trials for anti-cancer treatment. In the present work, we propose a novel approach to increase the number of potential SEGRAs by obtaining derivatives of synephrine, a molecule of natural origin. We synthesized 26 novel compounds from the class of synephrine derivatives and characterized them by HRMS, and 1H and 13C NMR. We evaluated in vitro anti-cancer effects in leukemia K562 and lymphoma Granta cells using the MTT assay and studied their potential affinity for the glucocorticoid receptor (GR) in silico using the molecular docking approach. The novel derivative 1-[4-(benzyloxy)phenyl]-2-(hexylamino)ethanol (10S-E2) with the highest GR affinity in silico exhibited cytotoxic activity against K562 and Granta cells after 24 h of treatment at the concentration of approximately 13 \u00b5M which correlated with its highest MolDock Score. The other compound with high GR affinity, 2-(hexylamino)-1-(4-nitrophenyl)ethanol (13S-G2), demonstrated cytotoxicity in both cell lines at concentrations of 50\u201370 \u00b5M. Overall, our results may provide a solid rationale for developing and further investigating synephrine derivatives as SEGRAs with anti-cancer activity.<\/jats:p>","DOI":"10.3390\/biom15010002","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T09:00:57Z","timestamp":1735030857000},"page":"2","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis and Anti-Cancer Activity In Vitro of Synephrine Derivatives"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-9391","authenticated-orcid":false,"given":"Ekaterina M.","family":"Zhidkova","sequence":"first","affiliation":[{"name":"Department of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeniya S.","family":"Oleynik","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Industrial Pharmacy, Lomonosov Institute of Fine Chemical Technologies, MIREA\u2014Russian Technological University, 86 Vernadsky Prospekt, Moscow 119571, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2511-3628","authenticated-orcid":false,"given":"Ekaterina A.","family":"Mikhina","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Industrial Pharmacy, Lomonosov Institute of Fine Chemical Technologies, MIREA\u2014Russian Technological University, 86 Vernadsky Prospekt, Moscow 119571, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0056-6040","authenticated-orcid":false,"given":"Daria V.","family":"Stepanycheva","sequence":"additional","affiliation":[{"name":"Department of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2675-089X","authenticated-orcid":false,"given":"Diana D.","family":"Grigoreva","sequence":"additional","affiliation":[{"name":"Department of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyubov E.","family":"Grebenkina","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Industrial Pharmacy, Lomonosov Institute of Fine Chemical Technologies, MIREA\u2014Russian Technological University, 86 Vernadsky Prospekt, Moscow 119571, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4040-4803","authenticated-orcid":false,"given":"Kirill V.","family":"Gordeev","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Kuban State Medical University, Ministry of Health of Russia, 4 Mitrofan Sedin Str., Krasnodar 350063, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina D.","family":"Savina","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Industrial Pharmacy, Lomonosov Institute of Fine Chemical Technologies, MIREA\u2014Russian Technological University, 86 Vernadsky Prospekt, Moscow 119571, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0830-3036","authenticated-orcid":false,"given":"Andrey V.","family":"Matveev","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Industrial Pharmacy, Lomonosov Institute of Fine Chemical Technologies, MIREA\u2014Russian Technological University, 86 Vernadsky Prospekt, Moscow 119571, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9710-8178","authenticated-orcid":false,"given":"Marianna G.","family":"Yakubovskaya","sequence":"additional","affiliation":[{"name":"Department of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, Russia"},{"name":"Institute of Medicine, Peoples\u2019 Friendship University of Russia, Miklukho-Maklaya St. 6, Moscow 117198, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1967-9637","authenticated-orcid":false,"given":"Ekaterina A.","family":"Lesovaya","sequence":"additional","affiliation":[{"name":"Department of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, Russia"},{"name":"Institute of Medicine, Peoples\u2019 Friendship University of Russia, Miklukho-Maklaya St. 6, Moscow 117198, Russia"},{"name":"Faculty of Oncology, I.P. Pavlov Ryazan State Medical University, Vysokovol\u2019tnaya Str. 9, Ryazan 390026, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103826","DOI":"10.1016\/j.critrevonc.2022.103826","article-title":"Corticosteroids in Oncology: Use, Overuse, Indications, Contraindications. An Italian Association of Medical Oncology (AIOM)\/Italian Association of Medical Diabetologists (AMD)\/Italian Society of Endocrinology (SIE)\/Italian Society of Pharmacology (SIF) Multidisciplinary Consensus Position Paper","volume":"180","author":"Faggiano","year":"2022","journal-title":"Crit. Rev. 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