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 F Liu; Joseph E Rice; Edmond J LaVoie

doi:10.1016/j.bmcl.2010.03.086

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. Epub 2010 Mar 30.

Authors

Mavurapu Satyanarayana¹, Young-Ah Kim, Suzanne G Rzuczek, Daniel S Pilch, Angela A Liu, Leroy F Liu, Joseph E Rice, Edmond J LaVoie

Affiliation

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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cell Line, Tumor
G-Quadruplexes*
Humans
Mice
Mice, Nude
Oxazoles / chemical synthesis
Oxazoles / chemistry*
Oxazoles / toxicity
RNA / chemistry*
Xenograft Model Antitumor Assays

Substances

Oxazoles
RNA