differentiation

Details

• Alternative Title:
  Bioorg Med Chem Lett
• Personal Author:
  Radhakrishnan, Sridhar ; Syed, Riyaz ; Takei, Hisashi ; Kobayashi, Ikei S. ; Nakamura, Eugene ; Sultana, Farheen ; Kamal, Ahmed ; Tenen, Daniel G. ; Kobayashi, Susumu S.
• Description:
  The tumor suppressor transcription factor CCAAT enhancer-binding protein α (C/EBPα) expression is downregulated in myeloid leukemias and enhancement of C/EBPα expression induces granulocytic differentiation in leukemic cells. Previously we reported that Styryl quinazolinones induce myeloid differentiation in HL-60 cells by upregulating C/EBPα expression. To identify more potent molecule that can induce leukemic cell differentiation we synthesized and evaluated new series of styryl quinazolinones, ethynyl styryl quinazolinones, styryl quinolinones and thienopyrimidinones. Thienopyrimidinones were found toxic and styryl quinolinones were found inactive. Ethynyl styryl quinazolinone 39 and styryl quinazolinone 5 were found active on par with the earlier reported analogues 1 and 2 suggesting that the 5-nitro furan-2-yl styryl quinazolinones find a real promise in leukemic cell differentiation. The improved potency of 5 suggested that further modifications in the 5-nitro furan-2-yl styryl quinazolinones can be at the phenyl substitution at the 3-position of the quinazolinone ring apart from the 5-position of the heteroaryl ring.
• Subjects:
  • Article
  • Styryl quinazolinones
  • Myeloid differentiation
  • CCAAT/enhancer binding protein
  • Thienopyrimidinone
  • Apoptosis
  • Alkynes
  • Antineoplastic Agents
  • CCAAT-Enhancer-Binding Protein-alpha
  • Cell Differentiation
  More +
• Source:
  Bioorg Med Chem Lett. 29(16):2286-2289
• Pubmed ID:
  31278031
• Pubmed Central ID:
  PMC8236261
• Document Type:
  Journal Article
• Funding:
  P01 HL131477/HL/NHLBI NIH HHSUnited States/ ; R21 CA178301/CA/NCI NIH HHSUnited States/ ; R35 CA197697/CA/NCI NIH HHSUnited States/ ; R01 DP000110/DP/NCCDPHP CDC HHSUnited States/ ; R01 CA169259/CA/NCI NIH HHSUnited States/
• Volume:
  29
• Issue:
  16
• Download URL:
  https://stacks.cdc.gov/view/cdc/107595/cdc_107595_DS1.pdf
• File Type:
  [PDF - 777.27 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:40a60a69a7dcfdbe2175bc601b6f380d5084648f7b9e79b5ad556a30f7a8ee0b