Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency.
The synthesis of a 24-membered macrocyclic hexaoxazole via ring-closing metathesis is described. The target compound selectively stabilizes G-quadruplex DNA with no detectable stabilization of duplex DNA. An MTT cytotoxicity assay indicated that this unsaturated macrocyclic hexaoxazole exhibits significant cytotoxicity toward P388, RPMI 8402, and KB3-1 cell lines with IC50 values of 45, 25, and 38 nM, respectively.
Satyanarayana
Mavurapu
M
Department of Pharmaceutical Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
Rzuczek
Suzanne G
SG
Lavoie
Edmond J
EJ
Pilch
Daniel S
DS
Liu
Angela
A
Liu
Leroy F
LF
Rice
Joseph E
JE
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004247:DNA / Q000737:chemistry*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D054856:G-Quadruplexes; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D009841:Oligonucleotides; D004247:DNA