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- Title
Styryl Quinazolinones as Potential Inducers of Myeloid Differentiation via Upregulation of C/EBPα.
- Authors
Sanda, Takaomi; Sridhar, Radhakrishnan; Hui, Liu Bee; Tenen, Daniel G.; Kobayashi, Ikei S.; Takei, Hisashi; Kobayashi, Susumu S.; Syed, Riyaz; Kamal, Ahmed
- Abstract
The CCAAT enhancer-binding protein α (C/EBPα) plays an important role in myeloid cell differentiation and in the enhancement of C/EBPα expression/activity, which can lead to granulocytic differentiation in acute myeloid leukemia (AML) cells. We found that styryl quinazolinones induce upregulation of C/EBPα expression, and thereby induce myeloid differentiation in human myeloid leukemia cell lines. We screened a series of active styryl quinazolinones and evaluated the structure–activity relationship (SAR) of these small molecules in inducing C/EBPα expression—thereby prompting the leukemic cells to differentiate. We observed that compound <bold>78</bold> causes differentiation at 3 μM concentration, while <bold>1</bold> induces differentiation at 10 μM concentration. We also observed an increase in the expression of neutrophil differentiation marker CD11b upon treatment with <bold>78</bold>. Both the C/EBPα and C/EBPε levels were found to be upregulated by treatment with <bold>78</bold>. These SAR findings are inspiration to develop further modified styryl quinazolinones, in the path of this novel differentiation therapy, which can contribute to the care of patients with AML.
- Subjects
STYRYL compounds; ACUTE myeloid leukemia; CCAAT enhancer binding proteins; QUINAZOLINONES; STRUCTURE-activity relationships
- Publication
Molecules, 2018, Vol 23, Issue 8, p1938
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules23081938