Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens

Midori A. Arai, Kyoko Uchida, Samir K. Sadhu, Firoj Ahmed, Takashi Koyano, Thaworn Kowithayakorn, Masami Ishibashi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The hedgehog (Hh) signaling pathway plays crucial roles in cell maintenance and proliferation during embryonic development. Naturally occurring Hh inhibitors were isolated from Artocarpus communis and Hyptis suaveolens using our previously constructed cell-based assay system. Bioactivity guided fractionation led to the isolation of 15 compounds, including seven new compounds (4, 5, 6, 7, and 9-11). The isolated compounds showed cytotoxicity against a cancer cell line (PANC1) in which Hh signaling was abnormally activated. Several compounds (12-14; GLI1 transcriptional inhibition IC50 = 7.6, 4.7, and 4.0 μM, respectively) inhibited Hh related protein (BCL2) expression. Moreover, compounds 1, 12, and 13 disrupted GLI1 and DNA complex formation.

Original languageEnglish
Pages (from-to)4150-4154
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number15
DOIs
Publication statusPublished - 2015 Jul 23
Externally publishedYes

Keywords

  • Artocarpus communis
  • Hedgehog signal
  • Hyptis suaveolens
  • Inhibitor
  • Natural products

ASJC Scopus subject areas

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

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  • Cite this

    Arai, M. A., Uchida, K., Sadhu, S. K., Ahmed, F., Koyano, T., Kowithayakorn, T., & Ishibashi, M. (2015). Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens. Bioorganic and Medicinal Chemistry, 23(15), 4150-4154. https://doi.org/10.1016/j.bmc.2015.06.058