Efficient synthesis and biological evaluation of demethyl geranylgeranoic acid derivatives

Akimori Wada, Fei Wang, Yoshitomo Suhara, Yumiko Yamano, Takashi Okitsu, Kimie Nakagawa, Toshio Okano

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Synthetic retinoids have generated in the fields of dermatology and oncology due to their potent anti-proliferative and differentiation activities. We efficiently synthesized different demethyl geranylgeranoic acid (GGA) analogs, and evaluated their biological activities. Among the demethyl analogs synthesized, 3-demethyl derivative exhibited the highest anti-proliferative activity in HL-60 cells. In addition, a 3-demethyl derivative induced apoptosis more potently than 9Z-retinoic acid. These activities were due to the high binding affinity of 3-demethyl derivative for retinoid receptors. We found that, in a conjugated polyene system combined with a methyl substituent, the position of the methyl played an important role in the regulation of gene transcription and apoptosis-inducing activity. These results provided useful information on the structure-activity relationships of GGA derivatives that function as acyclic retinoic acid analogs. This information is likely to be useful in the development of new anti-cancer drugs.

Original languageEnglish
Pages (from-to)5795-5806
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number16
DOIs
Publication statusPublished - 2010 Aug 15
Externally publishedYes

Fingerprint

Derivatives
Retinoids
Tretinoin
Dermatology
Apoptosis
Polyenes
Oncology
Transcription
Bioactivity
Genes
geranylgeranic acid
Pharmaceutical Preparations

Keywords

  • Coupling reaction
  • Demethyl analog
  • Geranylgeranoic acid
  • Retinoic acid analog
  • Retinoid receptors
  • Vinyl triflate

ASJC Scopus subject areas

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

Cite this

Efficient synthesis and biological evaluation of demethyl geranylgeranoic acid derivatives. / Wada, Akimori; Wang, Fei; Suhara, Yoshitomo; Yamano, Yumiko; Okitsu, Takashi; Nakagawa, Kimie; Okano, Toshio.

In: Bioorganic and Medicinal Chemistry, Vol. 18, No. 16, 15.08.2010, p. 5795-5806.

Research output: Contribution to journalArticle

Wada, Akimori ; Wang, Fei ; Suhara, Yoshitomo ; Yamano, Yumiko ; Okitsu, Takashi ; Nakagawa, Kimie ; Okano, Toshio. / Efficient synthesis and biological evaluation of demethyl geranylgeranoic acid derivatives. In: Bioorganic and Medicinal Chemistry. 2010 ; Vol. 18, No. 16. pp. 5795-5806.
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