Synthesis and biological evaluation of 1,2,5-oxadiazole N-oxide derivatives as potential hypoxic cytotoxins and DNA-binders.
Several new 1,2,5-oxadiazole N-oxide derivatives were synthesized to be tested both as potential selective hypoxic cell cytotoxins and as DNA-binding agents. The compounds prepared included bis(1,2,5-oxadiazole N-oxide) derivatives and oxadiazole rings linked to naphthyl residues. The compounds were tested for their cytotoxicity in oxia and hypoxia and they proved to be non-selective and less active than the parent compounds 3-formyl-4-phenyl-1,2,5-oxadiazole N2-oxide (3) and 3-chloromethyl-4-phenyl-1,2,5-oxadiazole N2-oxide (4). The DNA-affinity assays showed that the compounds tested have poor affinity for this biomolecule.
Cerecetto
H
H
Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Gral. Flores 2124, 11800 Montevideo, Uruguay.
González
M
M
Risso
M
M
Seoane
G
G
López de Ceráin
A
A
Ezpeleta
O
O
Monge
A
A
Suescun
L
L
Mombrú
A
A
Bruno
A M
AM
D000332:Aerobiosis; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002999:Clone Cells; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010087:Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D003603:Cytotoxins; D010069:Oxadiazoles; D010087:Oxides; D004247:DNA