Structure-activity relationship of C5-curcuminoids and synthesis of their molecular probes thereof

Hiroyuki Yamakoshi, Hisatsugu Ohori, Chieko Kudo, Atsuko Sato, Naoki Kanoh, Chikashi Ishioka, Hiroyuki Shibata, Yoshiharu Iwabuchi

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

A series of novel analogues of 1,5-bis(4-hydroxy-3-methoxyphenyl)-penta-(1E,4E)-1,4-dien-3-one (C5-curcumin), which is a natural analogue of curcumin isolated from the rhizomes of Curcuma domestica Val. (Zingiberacea), were synthesized and evaluated for their cytotoxicities against human colon cancer cell line HCT-116 to conclude the SAR of C5-curcuminoids for further development of their use in cancer chemotherapy: (1) Bis(arylmethylidene)acetone serves as a promising skeleton for eliciting cytotoxicity. (2) The 3-oxo-1,4-pentadiene structure is essential for eliciting cytotoxicity. (3) As for the extent of the aromatic substituents, hexasubstituted compounds exhibit strong activities, in which 3,4,5-hexasubstitution results in the highest potency. (5) The symmetry between two aryl rings is not an essential requirement for bis(arylmethylidene)acetones to elicit cytotoxicity. (6) para-Positions allows the installation of additional functional groups for use as molecular probes. By taking advantage of the SAR diagram, we have elaborated several advanced derivatives having GI50 of single-digit micromolar potencies that will function as molecular probes to target and/or report key biomolecules interacting with curcumin and C5-curcumin.

Original languageEnglish
Pages (from-to)1083-1092
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number3
DOIs
Publication statusPublished - 2010 Feb 1

Keywords

  • Bis(arylmethylidene)acetones
  • C-curcumin
  • Cancer chemotherapy
  • Curcumin
  • Cytotoxicity
  • Molecular probe

ASJC Scopus subject areas

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

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