{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:47:31Z","timestamp":1788223651872,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universit\u00e0 degli Studi di Palermo","award":["FFR-D15-008003"],"award-info":[{"award-number":["FFR-D15-008003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oleanolic acid (OA) and Lupeol (LU) belong to the class of natural triterpenes and are endowed with a wide range of biological activities, including cytotoxicity toward several cancer cell lines. In this context, we investigated a set of compounds obtained from the two natural precursors for the cytotoxicity against leukemia HL60 cells and the multidrug-resistant (MDR) variant HL60R. Six new semi-synthetic triterpenes have been synthetized, fully characterized, and were investigated together with other triterpenes compounds for their pharmacological mechanism of action. The interaction of the more cytotoxic compounds with the nuclear factor kappa B (NF-\u03baB) pathway has been also evaluated with the aid of docking. The lupane-like compounds were more active than the precursor, while the oleane-like compounds showed more complex behavior. Both OA and LU derivatives possess a similar interaction pattern with the p65 subunit of NF-\u03baB, justifying the similar trend in their ability to inhibit the binding of p65 to DNA. Further, some of the derivatives tested were able to increase I\u03baB-\u03b1 levels preventing the translocation of NF-\u03baB to the nucleus. In conclusion, this study offers a deeper insight on the pharmacological action of triterpenes toward leukemia cells, and it improves the background useful for the development of new anti-cancer drugs.<\/jats:p>","DOI":"10.3390\/ijms23126594","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T22:00:38Z","timestamp":1655157638000},"page":"6594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Synthesis, In Vitro and In Silico Analysis of New Oleanolic Acid and Lupeol Derivatives against Leukemia Cell Lines: Involvement of the NF-\u03baB Pathway"],"prefix":"10.3390","volume":"23","author":[{"given":"Gianfranco","family":"Fontana","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Biologiche, Chimiche e Farmaceutiche (STEBICEF), University of Palermo, Viale delle Scienze ed. 17, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7961-3894","authenticated-orcid":false,"given":"Natale","family":"Badalamenti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biologiche, Chimiche e Farmaceutiche (STEBICEF), University of Palermo, Viale delle Scienze ed. 17, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0583-0487","authenticated-orcid":false,"given":"Maurizio","family":"Bruno","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biologiche, Chimiche e Farmaceutiche (STEBICEF), University of Palermo, Viale delle Scienze ed. 17, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Castiglione","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica, University of Turin, Via Pietro Giuria 7, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Notarbartolo","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biologiche, Chimiche e Farmaceutiche (STEBICEF), University of Palermo, Viale delle Scienze ed. 17, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Poma","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biologiche, Chimiche e Farmaceutiche (STEBICEF), University of Palermo, Viale delle Scienze ed. 17, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Spinella","sequence":"additional","affiliation":[{"name":"Centro Grandi Apparecchiature (CGA)\u2014ATeN Center, University of Palermo, Via F. 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