Phenazine 5,10-dioxide derivatives as hypoxic selective cytotoxins.
The synthesis and evaluation as hypoxic selective cytotoxins of 2-amino- or 2-hydroxyphenazine 5,10-dioxide derivatives and reduced analogues are reported. In vitro cytotoxicities on V79 cells under hypoxic and aerobic conditions were determined. Some derivatives, such as 7(8)-bromo-2-hydroxyphenazine 5,10-dioxide, showed selective toxicity toward hypoxic cells and along with derivatives 7(8)-bromo-2-aminophenazine 5,10-dioxide and 7(8)-chloro-2-aminophenazine 5,10-dioxide behave as hypoxic trigger cytotoxins. These compounds represent interesting leads for further chemical modifications and biological studies.
Cerecetto
Hugo
H
Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Uruguay. hcerecet@fq.edu.uy
González
Mercedes
M
Lavaggi
Ma Laura
ML
Azqueta
Amaia
A
López de Cerain
Adela
A
Monge
Antonio
A
D000818:Animals; D001671:Biochemistry / Q000379:methods; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003603:Cytotoxins / Q000737:chemistry* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D010619:Phenazines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D003603:Cytotoxins; D010619:Phenazines; C071996:phenazine di-N-oxide