{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:00:52Z","timestamp":1789549252017,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"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":["IJMS"],"abstract":"<jats:p>Glucocorticoids (GCs) are widely used for treating hematological malignancies despite their multiple adverse effects. The biological response to GCs relies on glucocorticoid receptor (GR) transrepression (TR) that mediates the anticancer effects and transactivation (TA) associated with the side effects. Selective GR agonists (SEGRAs) preferentially activating GR TR could offer greater benefits in cancer treatment. One of the well-characterized SEGRAs, 2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium-chloride (CpdA), exhibited anticancer activity; however, its translational potential is limited due to chemical instability. To overcome this limitation, we obtained CpdA derivatives, CpdA-01\u2013CpdA-08, employing two synthetic strategies and studied their anti-tumor activity: 4-(1-hydroxy-2-(piperidin-1-yl)ethyl)phenol or CpdA-03 demonstrated superior GR affinity and stability compared to CpdA. In lymphoma Granta and leukemia CEM cell lines, CpdA-03 ligand exhibited typical SEGRA properties, inducing GR TR without triggering GR TA. CpdA-03 effects on cell viability, growth, and apoptosis were similar to the reference GR ligand, dexamethasone (Dex), and the source compound CpdA. In vivo testing of CpdA-03 activity against lymphoma on the transplantable P388 murine lymphoma model showed that CpdA-03 reduced tumor volume threefold, outperforming Dex and CpdA. In conclusion, in this work, we introduce a novel SEGRA CpdA-03 as a promising agent for lymphoma treatment with fewer side effects.<\/jats:p>","DOI":"10.3390\/ijms25168904","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T06:23:20Z","timestamp":1723789400000},"page":"8904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Synthesis and Anti-Cancer Activity of the Novel Selective Glucocorticoid Receptor Agonists of the Phenylethanolamine Series"],"prefix":"10.3390","volume":"25","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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyla R.","family":"Tilova","sequence":"additional","affiliation":[{"name":"Faculty of Normal and Pathological Anatomy, H.M. Berbekov Kabardino-Balkarian State University, Chernyshevsky Str 173, Nalchik 3620004, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timur I.","family":"Fetisov","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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8599-6833","authenticated-orcid":false,"given":"Kirill I.","family":"Kirsanov","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 (RUDN University), Miklukho-Maklaya St. 6, Moscow 117198, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny P.","family":"Kulikov","sequence":"additional","affiliation":[{"name":"Faculty of Oncology, I.P. Pavlov Ryazan State Medical University, Vysokovol\u2019tnaya Str 9, Ryazan 390026, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel D.","family":"Enikeev","sequence":"additional","affiliation":[{"name":"Oncogene Regulation Department, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5880-6822","authenticated-orcid":false,"given":"Irina V.","family":"Budunova","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Feinberg School of Medicine, Northwestern University, East Chicago Avenue 303, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9792-8432","authenticated-orcid":false,"given":"Gennadii A.","family":"Badun","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, M.V. Lomonosov Moscow State University, Leninskiye Gory 1, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5040-9937","authenticated-orcid":false,"given":"Maria G.","family":"Chernysheva","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, M.V. Lomonosov Moscow State University, Leninskiye Gory 1, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerii Z.","family":"Shirinian","sequence":"additional","affiliation":[{"name":"Laboratory of Heterocyclic Compounds, N.D. Zelinsky Institute of Organic Chemistry, 47, Leninsky Prospect, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 (RUDN University), Miklukho-Maklaya St. 6, Moscow 117198, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 (RUDN University), Miklukho-Maklaya St. 6, Moscow 117198, Russia"},{"name":"Faculty of Oncology, I.P. 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