Ulusoy, Nafia GokceEmirdag, SafiyeSozer, EceRadwan, Mohamed O.Ciftci, HalilibrahimAksel, MehranOzmen, Ali2023-01-122023-01-1220220141-81301879-0003https://doi.org/10.1016/j.ijbiomac.2022.09.257https://hdl.handle.net/11454/76584Chronic myelogenous leukemia (CML) is characterized by Philadelphia translocation arising from Bcr-Abl fusion gene, which encodes abnormal oncoprotein showing tyrosine kinase (TK) function. Certain mutations in kinase domain, off-target effects and resistance problems of current TK inhibitors require the discovery of novel Abl TK inhibitors. For this purpose, herein, we synthesized new gypsogenin derivatives (6a-l) and evaluated their anticancer effects towards CML cells along with healthy cell line and different leukemic cells. Among these compounds, compound 6l was found as the most active anti-leukemic agent against K562 CML cells compared to imatinib exerting less cytotoxicity towards PBMCs (healthy). This compound also revealed significant anti -leukemic effects against Jurkat cell line. Besides, compound 6l enhanced apoptosis in CML cells with 52.4 % when compared with imatinib (61.8 %) and inhibited Abl TK significantly with an IC50 value of 13.04 +/- 2.48 mu M in a large panel of kinases accentuating Abl TK-mediated apoptosis of compound 6l in CML cells. Molecular docking outcomes showed that compound 6l formed mainly crucial interactions in the ATP-binding cleft of Abl TK similar to that of imatinib. Ultimately, in silico pharmacokinetic evaluation of compound 6l indicated that this compound was endowed with anti-leukemic drug candidate features.en10.1016/j.ijbiomac.2022.09.257info:eu-repo/semantics/closedAccessChronic myelogenous leukemiaAbl tyrosine kinaseApoptosisGypsogenin derivativesImatinibMolecular dockingChronic Myelogenous LeukemiaBcr-AblTriterpenoid SaponinsReductive AminationIn-VitroResistanceImatinibKetonesRootsCellsArticle22214871499WOS:0008768290000042-s2.0-8513936149636195231Q1Q1