Macrocyclic hexaoxazoles: Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity.
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.
Satyanarayana
Mavurapu
M
Department of Medicinal Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
Kim
Young-Ah
YA
Rzuczek
Suzanne G
SG
Pilch
Daniel S
DS
Liu
Angela A
AA
Liu
Leroy F
LF
Rice
Joseph E
JE
LaVoie
Edmond J
EJ
D000818:Animals; D045744:Cell Line, Tumor; D054856:G-Quadruplexes; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D012313:RNA / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
D010080:Oxazoles; D012313:RNA