Hedgehog inhibitors from Withania somnifera

Tatsuro Yoneyama, Midori A. Arai, Samir K. Sadhu, Firoj Ahmed, Masami Ishibashi

研究成果: Article査読

16 被引用数 (Scopus)

抄録

The hedgehog (Hh) signaling pathway performs an important role in embryonic development and in cellular proliferation and differentiation. However, aberrant activation of the Hh signaling pathway is associated with tumorigenesis. Hh signal inhibition was evaluated using a cell-based assay system that targets GLI1-mediated transcription. Activity-guided isolation of the Withania somnifera MeOH extract led to the isolation of six compounds: withaferin A (1) and its derivatives (2-6). Compounds 1 and 2 showed strong inhibition of Hh/GLI1-mediated transcriptional activity with IC50 values of 0.5 and 0.6 μM, respectively. Compounds 1, 2, 3, and 6 were cytotoxic toward human pancreatic (PANC-1), prostate (DU145) and breast (MCF7) cancer cells. Furthermore, 1 also inhibited GLI1-DNA complex formation in EMSA.

本文言語English
ページ(範囲)3541-3544
ページ数4
ジャーナルBioorganic and Medicinal Chemistry Letters
25
17
DOI
出版ステータスPublished - 2015 8 3
外部発表はい

ASJC Scopus subject areas

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

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