@Article{or.2022.03539,
AUTHOR = {MESFER AL SHAHRANI, PRASANNA RAJAGOPALAN, MOHAMMAD ABOHASSAN, MOHAMMAD ALSHAHRANI, YASSER ALRAEY, REEM M. GAHTANI, SURESH RADHAKRISHNAN, KHLOOD DAGREERY},
TITLE = {Anticancer efficacy of 3-(4-isopropyl) benzylidene-8-ethoxy, 6-methyl, chroman-4-one (SBL-060), a novel, dual, estrogen receptor-Akt kinase inhibitor in acute myeloid leukemia cells},
JOURNAL = {Oncology Research},
VOLUME = {29},
YEAR = {2021},
NUMBER = {3},
PAGES = {149--157},
URL = {http://www.techscience.com/or/v29n3/49184},
ISSN = {1555-3906},
ABSTRACT = {Estrogen receptor (ER) α is expressed in a subset of patient-derived acute myeloid leukemia (AML) cells,
whereas Akt is predominantly expressed in most types of AML. Targeting AML with dual inhibitors is a novel
approach to combat the disease. Herein, we examined a novel small molecule, 3-(4-isopropyl) benzylidene-8-ethoxy,6-
methyl, chroman-4-one (SBL-060), capable of targeting AML cells by inhibiting ERα and Akt kinase. The chemical
properties of SBL-060 were identified by proton nuclear magnetic resonance (<sup>1</sup>
H-NMR), <sup>13</sup>C-NMR, and mass
spectroscopy. <i>In silico</i> docking was performed using an automated protocol with AutoDock-VINA. THP-1 and HL-60
cell lines were differentiated using phorbol 12-myristate 13-acetate. ERα inhibition was assessed using ELISA. The
MTT assay assessed cell viability. Flow cytometry was performed for cell cycle, apoptosis, and p-Akt analyses.
Chemical analysis identified the compound as 3-(4-isopropyl) benzylidene-8-ethoxy,6-methyl, chroman-4-one, which
showed high binding efficacy toward ER, with a ΔG<sub>binding</sub> score of −7.4 kcal/mol. SBL-060 inhibited ERα, exhibiting
IC<sub>50</sub> values of 448 and 374.3 nM in THP-1 and HL-60 cells, respectively. Regarding inhibited cell proliferation, GI<sub>50</sub>
values of SBL-060 were 244.1 and 189.9 nM for THP-1 and HL-60 cells, respectively. In addition, a dose-dependent
increase in sub G<sub>0</sub>/G<sub>1</sub> phase cell cycle arrest and total apoptosis was observed after treatment with SBL-060 in both
cell types. SBL-060 also dose-dependently increased the p-Akt-positive populations in both THP-1 and HL-60 cells.
Our results indicate that SBL-060 has excellent efficacy against differentiated AML cell types by inhibiting ER and Akt
kinase, warranting further preclinical evaluations.},
DOI = {10.32604/or.2022.03539}
}