Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency

Mavurapu Satyanarayana, Suzanne G. Rzuczek, Edmond J. LaVoie, Daniel S. Pilch, Angela Liu, Leroy-Fong Liu, Joseph E. Rice

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The synthesis of a 24-membered macrocyclic hexaoxazole via ring-closing metathesis is described. The target compound selectively stabilizes G-quadruplex DNA with no detectable stabilization of duplex DNA. An MTT cytotoxicity assay indicated that this unsaturated macrocyclic hexaoxazole exhibits significant cytotoxicity toward P388, RPMI 8402, and KB3-1 cell lines with IC50 values of 45, 25, and 38 nM, respectively.

Original languageEnglish
Pages (from-to)3802-3804
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number13
DOIs
Publication statusPublished - Jul 1 2008
Externally publishedYes

Fingerprint

G-Quadruplexes
Cytotoxicity
Inhibitory Concentration 50
Cell Line
DNA
Assays
Stabilization
Cells

Keywords

  • Cytotoxic
  • G-quadruplex stabilizer
  • Hexaoxazole
  • Macrocycle
  • Ring-closing metathesis
  • Selective
  • Synthesis

ASJC Scopus subject areas

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

Cite this

Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency. / Satyanarayana, Mavurapu; Rzuczek, Suzanne G.; LaVoie, Edmond J.; Pilch, Daniel S.; Liu, Angela; Liu, Leroy-Fong; Rice, Joseph E.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 13, 01.07.2008, p. 3802-3804.

Research output: Contribution to journalArticle

Satyanarayana, Mavurapu ; Rzuczek, Suzanne G. ; LaVoie, Edmond J. ; Pilch, Daniel S. ; Liu, Angela ; Liu, Leroy-Fong ; Rice, Joseph E. / Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency. In: Bioorganic and Medicinal Chemistry Letters. 2008 ; Vol. 18, No. 13. pp. 3802-3804.
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