Phenazine 5,10-dioxide derivatives as hypoxic selective cytotoxins: Part II. Structure-activity relationship studies.
The synthesis and evaluation as hypoxic selective cytotoxins of new derivatives of 2-amino or 2-hydroxyphenazine 5,10-dioxide are described. The compounds were developed as structural analogs of other bioreductive compounds and its in vitro cytotoxicities on V79 cells under hypoxic and aerobic conditions were determined. To gain insight into its mechanism of action electrochemical behavior, interaction with DNA experiments and QSAR studies were performed.
Cerecetto
H
H
Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay. hcerecet@fq.edu.uy
González
M
M
Lavaggi
M L
ML
Aravena
M A
MA
Rigol
C
C
Olea-Azar
C
C
Azqueta
A
A
de Cerain
A López
AL
Monge
A
A
Bruno
A M
AM
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry; D004563:Electrochemistry; D015394:Molecular Structure; D010619:Phenazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship; D013057:Spectrum Analysis
D003603:Cytotoxins; D010619:Phenazines; C071996:phenazine di-N-oxide; D004247:DNA