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

  • Bioorg Med Chem Lett. 2010 May 15;20(10):3150-4. doi: 10.1016/j.bmcl.2010.03.086.
Mavurapu Satyanarayana  1 ,  Young-Ah Kim ,  Suzanne G Rzuczek ,  Daniel S Pilch ,  Angela A Liu ,  Leroy F Liu ,  Joseph E Rice ,  Edmond J LaVoie
Affiliations
  • 1. Department of Medicinal Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
PMID: 20409709 DOI: 10.1016/j.bmcl.2010.03.086
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 IC(50) 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.