Macrocyclic hexaoxazoles: Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

A series of 24-membered macrocyclic hexaoxazoles containing one or two aminoalkyl substituents was synthesized and evaluated for cytotoxicity and for their ability to selectively stabilize G-quadruplex DNA and RNA. The most cytotoxic analog 4a, with IC50 values of 25 and 130 nM using KB3-1 and RPMI 8402 cells, is efficacious in vivo in athymic nude mice with a human tumor xenograft from the breast cancer cell line MDA-MB-435.

Original languageEnglish
Pages (from-to)3150-3154
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number10
DOIs
Publication statusPublished - May 15 2010
Externally publishedYes

Fingerprint

G-Quadruplexes
Cytotoxicity
Heterografts
Nude Mice
Tumors
Stabilization
Cells
RNA
DNA
Inhibitory Concentration 50
Breast Neoplasms
Cell Line
Neoplasms

Keywords

  • Antitumor
  • Athymic nude mice
  • Cytotoxicity
  • G-quadruplex DNA
  • G-quadruplex ligands
  • G-quadruplex RNA
  • Hexaoxazoles
  • Macrocycles
  • MDA-MB-435 xenograft

ASJC Scopus subject areas

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

Cite this

Macrocyclic hexaoxazoles : Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity. / Satyanarayana, Mavurapu; Kim, Young Ah; Rzuczek, Suzanne G.; Pilch, Daniel S.; Liu, Angela A.; Liu, Leroy-Fong; Rice, Joseph E.; LaVoie, Edmond J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 10, 15.05.2010, p. 3150-3154.

Research output: Contribution to journalArticle

Satyanarayana, Mavurapu ; Kim, Young Ah ; Rzuczek, Suzanne G. ; Pilch, Daniel S. ; Liu, Angela A. ; Liu, Leroy-Fong ; Rice, Joseph E. ; LaVoie, Edmond J. / Macrocyclic hexaoxazoles : Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 10. pp. 3150-3154.
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