Indeno[1,2-c]isoquinolines as enhancing agents on all-trans retinoic acid-mediated differentiation of human myeloid leukemia cells

Seung Hyun Kim, Sang Mi Oh, Ju Han Song, Dae Ho Cho, Quynh Manh Le, Suh Hee Lee, Won Jea Cho, Tae Sung Kim

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8 Citations (Scopus)

Abstract

Induction of differentiation is a new and promising approach to cancer therapy, well illustrated by the treatment of acute myeloid leukemia with all-trans retinoic acid (ATRA). Using combination of ATRA and chemotherapy, adverse effects such as retinoic acid syndrome have decreased, and long-term survival has improved. In this study, we demonstrated that the indeno[1,2-c]isoquinolines markedly enhanced differentiation of human myeloid leukemia HL-60 and NB4 cells when simultaneously combined with a low dose of ATRA. Of the tested compounds, 6-(4-methoxybenzyl)-2,11-dimethyl-6H,11H-indeno[1,2-c]isoquinolin-5-one (IIQ-16), an indeno[1,2-c]isoquinoline derivative, showed the highest differentiation-enhancing activity via a pathway involved with protein kinase C, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. The ability to enhance the differentiation potential of ATRA by IIQ-16 may improve outcomes in the therapy of acute promyelocytic leukemia.

Original languageEnglish
Pages (from-to)1125-1132
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number3
DOIs
Publication statusPublished - 2008 Feb 1

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Keywords

  • All-trans retinoic acid
  • Differentiation
  • Indenoisoquinoline
  • Leukemia

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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