Synthesis and Tumor-promoting Activities of 12-Epi-phorbol-12,13-dibutyrate

Kazuhiro Irie, Akifumi Nakahara, Yasuyuki Ikawa, Minoru Tanaka, Yu Nakagawa, 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
Publication statusPublished - Nov 2000
Externally publishedYes

Fingerprint

Phorbol 12,13-Dibutyrate
protein kinase C
Tumors
Proteins
Human herpesvirus 4
Protein Kinase C
Stereochemistry
neoplasms
synthesis
stereochemistry
Antigens
Bioactivity
Viruses
superoxide anion
Peptides
skeleton
bioactive properties
Neoplasms
Esters
esters

Keywords

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

ASJC Scopus subject areas

  • Food Science
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biotechnology
  • Chemistry (miscellaneous)
  • Applied Microbiology and Biotechnology
  • Bioengineering

Cite this

Irie, K., Nakahara, A., Ikawa, Y., Tanaka, M., Nakagawa, Y., Nakamura, Y., ... Wender, P. A. (2000). Synthesis and Tumor-promoting Activities of 12-Epi-phorbol-12,13-dibutyrate. Bioscience, Biotechnology and Biochemistry, 64(11), 2429-2436.

Synthesis and Tumor-promoting Activities of 12-Epi-phorbol-12,13-dibutyrate. / Irie, Kazuhiro; Nakahara, Akifumi; Ikawa, Yasuyuki; Tanaka, Minoru; Nakagawa, Yu; Nakamura, Yoshimasa; Ohigashi, Hajime; Wender, Paul A.

In: Bioscience, Biotechnology and Biochemistry, Vol. 64, No. 11, 11.2000, p. 2429-2436.

Research output: Contribution to journalArticle

Irie, K, Nakahara, A, Ikawa, Y, Tanaka, M, Nakagawa, Y, Nakamura, Y, Ohigashi, H & Wender, PA 2000, 'Synthesis and Tumor-promoting Activities of 12-Epi-phorbol-12,13-dibutyrate', Bioscience, Biotechnology and Biochemistry, vol. 64, no. 11, pp. 2429-2436.
Irie K, Nakahara A, Ikawa Y, Tanaka M, Nakagawa Y, Nakamura Y et al. Synthesis and Tumor-promoting Activities of 12-Epi-phorbol-12,13-dibutyrate. Bioscience, Biotechnology and Biochemistry. 2000 Nov;64(11):2429-2436.
Irie, Kazuhiro ; Nakahara, Akifumi ; Ikawa, Yasuyuki ; Tanaka, Minoru ; Nakagawa, Yu ; Nakamura, Yoshimasa ; Ohigashi, Hajime ; Wender, Paul A. / Synthesis and Tumor-promoting Activities of 12-Epi-phorbol-12,13-dibutyrate. In: Bioscience, Biotechnology and Biochemistry. 2000 ; Vol. 64, No. 11. pp. 2429-2436.
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