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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

MESFER AL SHAHRANI1,2,*, PRASANNA RAJAGOPALAN1,2, MOHAMMAD ABOHASSAN1, MOHAMMAD ALSHAHRANI1, YASSER ALRAEY1, REEM M. GAHTANI1, SURESH RADHAKRISHNAN3, KHLOOD DAGREERY4

1 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
2 Central Research Laboratory, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
3 PG and Research Department of Chemistry, Presidency College, Chennai, Tamil Nadu, India
4 Regional Laboratory and Central Blood Bank, Jazan, Saudi Arabia

* Corresponding Author: Mesfer Al Shahrani, email

Oncology Research 2021, 29(3), 149-157. https://doi.org/10.32604/or.2022.03539

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 (1 H-NMR), 13C-NMR, and mass spectroscopy. In silico 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 ΔGbinding score of −7.4 kcal/mol. SBL-060 inhibited ERα, exhibiting IC50 values of 448 and 374.3 nM in THP-1 and HL-60 cells, respectively. Regarding inhibited cell proliferation, GI50 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 G0/G1 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.

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APA Style
SHAHRANI, M.A., RAJAGOPALAN, P., ABOHASSAN, M., ALSHAHRANI, M., ALRAEY, Y. et al. (2021). 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. Oncology Research, 29(3), 149-157. https://doi.org/10.32604/or.2022.03539
Vancouver Style
SHAHRANI MA, RAJAGOPALAN P, ABOHASSAN M, ALSHAHRANI M, ALRAEY Y, GAHTANI RM, et al. 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. Oncol Res. 2021;29(3):149-157 https://doi.org/10.32604/or.2022.03539
IEEE Style
M.A. SHAHRANI et al., "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," Oncol. Res., vol. 29, no. 3, pp. 149-157. 2021. https://doi.org/10.32604/or.2022.03539



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