Structural optimization of 10-methyl-aplog-1, a simplified analog of debromoaplysiatoxin, as an anticancer lead

Masayuki Kikumori, Ryo C. Yanagita, Harukuni Tokuda, Kiyotake Suenaga, Hiroshi Nagai, Kazuhiro Irie

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aplog-1 is a simplified analog of debromoaplysiatoxin (DAT) with potent tumor-promoting and proinflammatory activities. Aplog-1 and DAT exhibited anti-proliferative activities against several human cancer cell lines, whereas aplog-1 did not have tumor-promoting nor proinflammatory activities. We have recently found 10-methyl-aplog-1 (1) to have strong anti-proliferative activity compared with aplog-1. To further investigate the structural factors involved in the tumor-promoting, proinflammatory, and anti-proliferative activities, two dimethyl derivatives of aplog-1 (2, 3) were synthesized, where two methyl groups were installed at positions 4 and 10 or 10 and 12. 10,12-Dimethyl-aplog-1 (2) had stronger inhibitory effects on the growth of several human cancer cell lines than 1 and DAT, but exhibited no tumor-promoting and proinflammatory activities. In contrast, 4,10-dimethyl-aplog-1 (3) displayed weak tumor-promoting and proinflammatory activities along with anti-proliferative activity similar to that of 1 and DAT. Compound 2 would be the optimized seed for anticancer drugs among the simplified analogs of DAT.

Original languageEnglish
Pages (from-to)221-231
Number of pages11
JournalBioscience, Biotechnology and Biochemistry
Volume80
Issue number2
DOIs
Publication statusPublished - 2016

Fingerprint

Structural optimization
Tumors
Neoplasms
Cells
Cell Line
Seed
debromoaplysiatoxin
Derivatives
Seeds
Pharmaceutical Preparations
Growth

Keywords

  • Anti-proliferative
  • Cancer
  • Debromoaplysiatoxin
  • Protein kinase C
  • Tumor promoter

ASJC Scopus subject areas

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

Cite this

Structural optimization of 10-methyl-aplog-1, a simplified analog of debromoaplysiatoxin, as an anticancer lead. / Kikumori, Masayuki; Yanagita, Ryo C.; Tokuda, Harukuni; Suenaga, Kiyotake; Nagai, Hiroshi; Irie, Kazuhiro.

In: Bioscience, Biotechnology and Biochemistry, Vol. 80, No. 2, 2016, p. 221-231.

Research output: Contribution to journalArticle

Kikumori, Masayuki ; Yanagita, Ryo C. ; Tokuda, Harukuni ; Suenaga, Kiyotake ; Nagai, Hiroshi ; Irie, Kazuhiro. / Structural optimization of 10-methyl-aplog-1, a simplified analog of debromoaplysiatoxin, as an anticancer lead. In: Bioscience, Biotechnology and Biochemistry. 2016 ; Vol. 80, No. 2. pp. 221-231.
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