Synthesis and tumor-promoting activities of 12-Epi-phorbol-12,13-dibutyrate

Kazuhiro Irie, Akifumi Nakahara, Yasuyuki Ikawa, Minoru Tanaka, Yu Nakagavva, Yoshimasa Nakamura, Hajime Ohigashi, Paul A. Wender

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

12-Epi-phorbol-12,13-dibutyrate (1), the C12-epimer of the most frequently used phorbol ester probe, phorbol-12,13-dibutyrate (PDBu), has been synthesized from phorbol in 9 steps in order to investigate the structural requirements for tumor-promoting activity. Compound 1 showed about 100-fold weaker in vitro biological activities related to in vivo tumor promotion, Epstein-Barr virus early antigen (EBV-EA)-inducing ability, superoxide (O2) generation-inducing ability, and binding to the protein kinase C (PKC) regulatory domain surrogate peptides. The results indicated that the β-stereochemistry at position 12 of the phorbol skeleton is important for optimal activity. Binding selectivity to each PKC C1 domain of 1 was almost equal to that of PDBu.

Original languageEnglish
Pages (from-to)2429-2436
Number of pages8
JournalBioscience, Biotechnology and Biochemistry
Volume64
Issue number11
DOIs
Publication statusPublished - Jan 1 2000
Externally publishedYes

Keywords

  • 12-epi-phorbol-12,13-dibutyrate
  • Epstein-Barr virus
  • Phorbol ester
  • Protein kinase C
  • Tumor promoter

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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  • Cite this

    Irie, K., Nakahara, A., Ikawa, Y., Tanaka, M., Nakagavva, Y., Nakamura, Y., Ohigashi, H., & Wender, P. A. (2000). Synthesis and tumor-promoting activities of 12-Epi-phorbol-12,13-dibutyrate. Bioscience, Biotechnology and Biochemistry, 64(11), 2429-2436. https://doi.org/10.1271/bbb.64.2429