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.
Department of Pharmaceutical Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
Mavurapu
M
Satyanarayana
Suzanne G
SG
Rzuczek
Edmond J
EJ
Lavoie
Daniel S
DS
Pilch
Angela
A
Liu
Leroy F
LF
Liu
Joseph E
JE
Rice
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