Macrocyclic biphenyl tetraoxazoles: Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity

Gifty A. Blankson, Daniel S. Pilch, Angela A. Liu, Leroy-Fong Liu, Joseph E. Rice, Edmond J. Lavoie

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A series of macrocyclic biphenyl tetraoxazoles was synthesized. The latter stages of the synthetic approach allowed for the addition of varied N-protected α-amino acids, which were subsequently deprotected and condensed to provide the desired macrocycles. Improved yields could be realized in the macrocyclization step of their synthesis relative to other macrocyclic G-quadruplex stabilizers. These 24-membered macrocycles were evaluated for their ability to stabilize G-quadruplex DNA and for their relative cytotoxicity against human tumor cells. These biphenyl tetraoxazoles were not strong ligands for G-quadruplex DNA relative to other macrocyclic polyoxazoles. This reduced stabilizing potential did correlate with their comparatively lower cytotoxic activity as observed in the human tumor cell lines, RPMI 8402 and KB3-1. These studies provide useful insights into the conformational requirements for the development of selective and more potent G-quadruplex ligands.

Original languageEnglish
Pages (from-to)4511-4520
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number15
DOIs
Publication statusPublished - Aug 1 2013
Externally publishedYes

Fingerprint

G-Quadruplexes
Tumors
Cells
Ligands
DNA
Cytotoxicity
Amino Acids
Tumor Cell Line
diphenyl
Neoplasms

Keywords

  • Biphenyl
  • Cytotoxicity
  • G-quadruplex
  • G-quadruplex ligand
  • Macrocycle
  • Oxazoles

ASJC Scopus subject areas

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

Cite this

Macrocyclic biphenyl tetraoxazoles : Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity. / Blankson, Gifty A.; Pilch, Daniel S.; Liu, Angela A.; Liu, Leroy-Fong; Rice, Joseph E.; Lavoie, Edmond J.

In: Bioorganic and Medicinal Chemistry, Vol. 21, No. 15, 01.08.2013, p. 4511-4520.

Research output: Contribution to journalArticle

Blankson, Gifty A. ; Pilch, Daniel S. ; Liu, Angela A. ; Liu, Leroy-Fong ; Rice, Joseph E. ; Lavoie, Edmond J. / Macrocyclic biphenyl tetraoxazoles : Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity. In: Bioorganic and Medicinal Chemistry. 2013 ; Vol. 21, No. 15. pp. 4511-4520.
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