{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:09:08Z","timestamp":1792789748509,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T00:00:00Z","timestamp":1652832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PON R&amp;I funds 2014\u20132020","award":["CUP: E66C18001320007, AIM1872330, activity 1"],"award-info":[{"award-number":["CUP: E66C18001320007, AIM1872330, activity 1"]}]},{"name":"PON R&amp;I funds 2014\u20132020","award":["02769.N.VLY"],"award-info":[{"award-number":["02769.N.VLY"]}]},{"name":"PON R&amp;I funds 2014\u20132020","award":["57722172126"],"award-info":[{"award-number":["57722172126"]}]},{"name":"Ministry of Health (Directorate General for Animal Health and Veterinary Medicines) \u201cDosing of enzymatic activities in rat microsomes\u201d (2018\u20132022)","award":["CUP: E66C18001320007, AIM1872330, activity 1"],"award-info":[{"award-number":["CUP: E66C18001320007, AIM1872330, activity 1"]}]},{"name":"Ministry of Health (Directorate General for Animal Health and Veterinary Medicines) \u201cDosing of enzymatic activities in rat microsomes\u201d (2018\u20132022)","award":["02769.N.VLY"],"award-info":[{"award-number":["02769.N.VLY"]}]},{"name":"Ministry of Health (Directorate General for Animal Health and Veterinary Medicines) \u201cDosing of enzymatic activities in rat microsomes\u201d (2018\u20132022)","award":["57722172126"],"award-info":[{"award-number":["57722172126"]}]},{"name":"University (Programma Ricerca di Ateneo UNICT Pia.Ce.Ri 2020-2022 linea 2","award":["CUP: E66C18001320007, AIM1872330, activity 1"],"award-info":[{"award-number":["CUP: E66C18001320007, AIM1872330, activity 1"]}]},{"name":"University (Programma Ricerca di Ateneo UNICT Pia.Ce.Ri 2020-2022 linea 2","award":["02769.N.VLY"],"award-info":[{"award-number":["02769.N.VLY"]}]},{"name":"University (Programma Ricerca di Ateneo UNICT Pia.Ce.Ri 2020-2022 linea 2","award":["57722172126"],"award-info":[{"award-number":["57722172126"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This paper reports on a novel series of tyrosine kinase inhibitors (TKIs) potentially useful for the treatment of chronic myeloid leukemia (CML). The newly designed and synthesized compounds are structurally related to nilotinib (NIL), a second-generation oral TKI, and to a series of imatinib (IM)-based TKIs, previously reported by our research group, these latter characterized by a hybrid structure between TKIs and heme oxygenase-1 (HO-1) inhibitors. The enzyme HO-1 was selected as an additional target since it is overexpressed in many cases of drug resistance, including CML. The new derivatives 1a\u2013j correctly tackle the chimeric protein BCR-ABL. Therefore, the inhibition of TK was comparable to or higher than NIL and IM for many novel compounds, while most of the new analogs showed only moderate potency against HO-1. Molecular docking studies revealed insights into the binding mode with BCR-ABL and HO-1, providing a structural explanation for the differential activity. Cytotoxicity on K562 CML cells, both NIL-sensitive and -resistant, was evaluated. Notably, some new compounds strongly reduced the viability of K562 sensitive cells.<\/jats:p>","DOI":"10.3390\/molecules27103220","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T23:14:26Z","timestamp":1652915666000},"page":"3220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel Tyrosine Kinase Inhibitors to Target Chronic Myeloid Leukemia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9172-5768","authenticated-orcid":false,"given":"Valeria","family":"Ciaffaglione","sequence":"first","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8961-5818","authenticated-orcid":false,"given":"Valeria","family":"Consoli","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0201-1745","authenticated-orcid":false,"given":"Sebastiano","family":"Intagliata","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8728-8857","authenticated-orcid":false,"given":"Agostino","family":"Marrazzo","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2160-4164","authenticated-orcid":false,"given":"Giuseppe","family":"Romeo","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-0308","authenticated-orcid":false,"given":"Valeria","family":"Pittal\u00e0","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0787-7070","authenticated-orcid":false,"given":"Khaled","family":"Greish","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama 329, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6314-6029","authenticated-orcid":false,"given":"Luca","family":"Vanella","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0668-1260","authenticated-orcid":false,"given":"Giuseppe","family":"Floresta","sequence":"additional","affiliation":[{"name":"Department of Analytical, Environmental and Forensic Sciences, King\u2019s College London, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5039-2151","authenticated-orcid":false,"given":"Antonio","family":"Rescifina","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6458-3717","authenticated-orcid":false,"given":"Loredana","family":"Salerno","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5973-1495","authenticated-orcid":false,"given":"Valeria","family":"Sorrenti","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1056\/NEJM198810133191506","article-title":"The molecular genetics of Philadelphia chromosome-positive leukemias","volume":"319","author":"Kurzrock","year":"1988","journal-title":"N. Engl. J. 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