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

doi:10.1271/bbb.64.2429

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 journal › Article › peer-review

8 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 language	English
Pages (from-to)	2429-2436
Number of pages	8
Journal	Bioscience, Biotechnology and Biochemistry
Volume	64
Issue number	11
DOIs	https://doi.org/10.1271/bbb.64.2429
Publication status	Published - 2000
Externally published	Yes

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

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.",

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

author = "Kazuhiro Irie and Akifumi Nakahara and Yasuyuki Ikawa and Minoru Tanaka and Yu Nakagavva and Yoshimasa Nakamura and Hajime Ohigashi and Wender, {Paul A.}",

year = "2000",

doi = "10.1271/bbb.64.2429",

language = "English",

volume = "64",

pages = "2429--2436",

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T1 - Synthesis and tumor-promoting activities of 12-Epi-phorbol-12,13-dibutyrate

AU - Irie, Kazuhiro

AU - Nakahara, Akifumi

AU - Ikawa, Yasuyuki

AU - Tanaka, Minoru

AU - Nakagavva, Yu

AU - Nakamura, Yoshimasa

AU - Ohigashi, Hajime

AU - Wender, Paul A.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - 12-epi-phorbol-12,13-dibutyrate

KW - Epstein-Barr virus

KW - Phorbol ester

KW - Protein kinase C

KW - Tumor promoter

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JO - Bioscience, Biotechnology and Biochemistry

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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